An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
- Conditions
- Hypercholesterolaemia
- Interventions
- Registration Number
- NCT02890992
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C \>=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre \[mmol/L\]) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period.
Secondary Objective:
* To evaluate the safety and tolerability of alirocumab.
* To evaluate the pharmacokinetics profile of alirocumab.
* To evaluate the effects of alirocumab on other lipid parameters.
- Detailed Description
For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).
For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 \[+1\] weeks, open-label dose finding treatment period: 12 weeks).
Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4.
For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 - Alirocumab 30 mg Q2W: <50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg statins Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg statins Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg statins Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg statins Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg statins Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg statins Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg nicotinic acid Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg statins Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg alirocumab SAR236553 (REGN727) Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg statins Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg ezetimibe Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg fenofibrate Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg nicotinic acid Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg ezetimibe Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg omega-3 fatty acids Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg fenofibrate Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg nicotinic acid Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg fenofibrate Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg ezetimibe Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg nicotinic acid Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg omega-3 fatty acids Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg ezetimibe Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg fenofibrate Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg omega-3 fatty acids Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg nicotinic acid Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg ezetimibe Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg fenofibrate Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg nicotinic acid Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg ezetimibe Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg fenofibrate Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg ezetimibe Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg fenofibrate Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg omega-3 fatty acids Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg nicotinic acid Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg ezetimibe Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg fenofibrate Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg nicotinic acid Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg cholestyramine Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg cholestyramine Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 40 mg Q2W: <50 kg cholestyramine Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg cholestyramine Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg cholestyramine Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg cholestyramine Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 4 - Alirocumab 150 mg Q4W: <50 kg cholestyramine Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg cholestyramine Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. Cohort 1 - Alirocumab 30 mg Q2W: <50 kg omega-3 fatty acids Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 75 mg Q4W: <50 kg omega-3 fatty acids Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg omega-3 fatty acids Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg omega-3 fatty acids Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 Baseline, Week 8 Percent change in calculated LDL-C was defined as 100\*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period \& within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 \& 2) or +35 days (for Cohorts 3 \& 4). Adjusted Least-squares (LS) mean \& standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W \[\<50 kg\], 40 mg Q2W \[\<50 kg\], 50 mg Q2W \[\>=50 kg\], 75 mg Q2W \[\>=50 kg\], 75 mg Q4W \[\<50 kg\],150 mg Q4W \[\>=50 kg\], 150 mg Q4W \[\<50 kg\] and 300 mg Q4W (\[\>=50 kg\] dose), time point \& dose/dose regimen-by-time point interaction.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Percent Change From Baseline in Apolipoprotein A-1 at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Absolute Change From Baseline in Apolipoprotein B at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Absolute Change From Baseline in HDL-C at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 Baseline, Week 8 Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 At Week 8 Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 At Week 8 Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 Baseline, Week 12 Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model.
Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Percent Change From Baseline in Lipoprotein(a) at Week 8 Baseline, Week 8 Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Percent Change From Baseline in Fasting Triglyceride at Week 8 Baseline, Week 8 Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Absolute Change From Baseline in Lipoprotein(a) at Week 8 Baseline, Week 8 Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Absolute Change From Baseline in Fasting Triglyceride at Week 8 Baseline, Week 8 Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 Baseline, Week 8 Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Trial Locations
- Locations (16)
Investigational Site Number 2030002
🇨🇿Zlin, Czechia
Investigational Site Number 8400005
🇺🇸Charlotte, North Carolina, United States
Investigational Site Number 8400001
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 8400002
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 1240001
🇨🇦Quebec, Canada
Investigational Site Number 2030003
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number 2500001
🇫🇷Bron Cedex, France
Investigational Site Number 5780001
🇳🇴Oslo, Norway
Investigational Site Number 2030001
🇨🇿Brno, Czechia
Investigational Site Number 5280001
🇳🇱Amsterdam, Netherlands
Investigational Site Number 7100001
🇿🇦Parow, South Africa
Investigational Site Number 7240004
🇪🇸A Coruna, Spain
Investigational Site Number 7240001
🇪🇸Madrid, Spain
Investigational Site Number 6430001
🇷🇺Kemerovo, Russian Federation
Investigational Site Number 7520001
🇸🇪Stockholm, Sweden
Investigational Site Number 6430004
🇷🇺Saint-Petersburg, Russian Federation