Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia
- Registration Number
- NCT04143724
- Lead Sponsor
- Celgene
- Brief Summary
This is a Phase 2a study to evaluate the safety and pharmacokinetics (PK) of luspatercept in pediatric participants with β-thalassemia.
The study will be conducted in 2 parts for both transfusion-dependent (TD) and non-transfusion-dependent (NTD) β-thalassemia participants: TD Part A will be in adolescent participants aged 12 to \<18 years with two dose escalation cohorts, followed by a dose expansion cohorts. NTD Part A will be conducted in the same age group participants as TD Part A with dose confirmation and expansion cohorts. After Part A TD participants have completed at least one year of treatment, all available safety data from Part A adolescent participants will be evaluated before initiating TD and NTD Part B in the age group from 6 to \<12 years old. Part B will consist of two dose escalation cohorts for TD and two dose escalation cohorts for NTD.
Upon completion of the Treatment Period, participants of any cohort who are benefiting from the study treatment, will be offered the opportunity to continue luspatercept treatment in the Long-term Treatment Period for up to 5 years from their first dose.
Participants who discontinue study treatment at any time will continue in the Posttreatment Follow-up Period for at least 5 years from their first dose of luspatercept, or 3 years from their last dose, whichever occurs later, or until they withdraw consent/assent, are lost to follow-up, or the End of Trial, whichever occurs first.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 99
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kg ACE-536 - Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kg ACE-536 - Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kg ACE-536 - Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg ACE-536 - Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kg ACE-536 - Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kg ACE-536 - Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 years ACE-536 - Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg ACE-536 - Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kg ACE-536 -
- Primary Outcome Measures
Name Time Method Pharmacokinetics - AUC Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Area under the curve
Pharmacokinetics (PK) - CL/F Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Apparent oral clearance
Pharmacokinetics (PK) - t1/2 Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Half-life
Pharmacokinetics (PK) - Vd/F Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Apparent volume of distribution
Determination of the Recommended Dose (RD Cycle 1 up to the day before Cycle 2 Day 1 or Study Day 22 if not receiving the second treatment cycle Determine the recommended dose of luspatercept that is safe and tolerable in pediatric participants with transfusion-dependent B-thalassemia or non-transfusion-dependent β-thalassemia
Pharmacokinetics - Cmax Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Maximum serum concentration of drug
- Secondary Outcome Measures
Name Time Method Mean change in hemoglobin levels for non-transfusion-dependent β-thalassemia participants 12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years Change from baseline as continuous variable
Immunogenicity Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year Frequency of antidrug antibodies (ADA)
Mean change from baseline in serum ferritin 12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years Change from baseline as continuous variable
Safety - Incidence of Adverse Events (AEs) From enrollment until at least 9 weeks after last dose of study treatment An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE
Mean change in Red Blood Cell (RBC) Transfusion Burden for transfusion-dependent β-thalassemia participants 12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years Change from baseline as continuous variable
Mean change from baseline in mean daily dose of iron chelation therapy (ICT) 12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years Change from baseline as continuous variable
Trial Locations
- Locations (26)
Local Institution - 601
🇺🇸Los Angeles, California, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Shenzhen Second People's Hospital
🇨🇳Shenzhen, Guangdong, China
Local Institution - 904
🇨🇳Nanning, GX, China
West China Hospital - Sichuan University
🇨🇳Chengdu, Sichuan, China
Sun Yat-sen Memorial Hospital, Sun Yat-Sen University
🇨🇳Guangzhou, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, China
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitatsklinikum Ulm
🇩🇪Ulm, Germany
Scroll for more (16 remaining)Local Institution - 601🇺🇸Los Angeles, California, United States