A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Patients With Non-Transfusion Dependent β-Thalassemia Intermedia
Overview
- Phase
- Phase 2
- Intervention
- sapablursen
- Conditions
- Beta Thalassemia Intermedia
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 29
- Locations
- 19
- Primary Endpoint
- Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The purpose was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.
Detailed Description
This was a multi-center, randomized, open-label study in up to 29 participants. The duration of participation for each subject in the study was approximately 29 months and included an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willingness to comply with study procedures
- •Clinical diagnosis of Beta-Thalassemia Intermedia with genotypic confirmation
- •Non-transfusion dependent, as defined by: no more than 6 transfusions in the past 12-month period, and no transfusions in the 8-week period prior to Day 1
- •Mean Hb within the range of 6.0-10.0 g/dL, inclusive at Screening
- •LIC within the range of 3.0-20.0 mg Fe/g dry weight, inclusive
- •If using chelators, must be on a stable dose for at least 3 months with liver iron concentration (LIC) \> 5.0 mg iron (Fe) per gram of dry weight of liver (Fe/g) dry weight and serum ferritin \> 300 nanograms per milliliter (ng/mL)
- •Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal
- •Males must be surgically sterile, abstinent or using an acceptable contraceptive method
Exclusion Criteria
- •Clinically significant abnormalities in lab values, medical history, or physical examination
- •α-globin gene triplication
- •Symptomatic splenomegaly
- •Platelet count \< lower limit of normal (LLN) or \> 1,000 x 10\^9/L
- •Significant concurrent/recent coagulopathy, history of non-traumatic significant bleeding; history of immune thrombocytopenic purpura (ITP); current use of SC anti-coagulants; history of thrombotic events, including stroke or DVT
- •Clinically significant renal, liver or cardiac dysfunction
- •Uncontrolled hypertension (\> 140 mm Hg systolic or \> 90 mm Hg diastolic)
- •Fasting blood glucose \> 2.0 × upper limit of normal (ULN)
- •Inability to have a magnetic resonance imaging (MRI) scan
- •Known history or positive test for human immunodeficiency virus (HIV), hepatitis C (HCV), or hepatitis B (HBV)
Arms & Interventions
Cohort A: Sapablursen
Subjects initially received 30 mg/0.3 mL of sapablursen by (subcutaneous) SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks.
Intervention: sapablursen
Cohort B: Sapablursen
Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks
Intervention: sapablursen
Cohort C: Sapablursen
Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks.
Intervention: sapablursen
Outcomes
Primary Outcomes
Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27
Time Frame: Baseline and Week 27
Blood hemoglobin
Secondary Outcomes
- Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53(Week 53)
- Percentage of Participants With a ≥1.0 Milligrams of Iron Per Grams of Dry Weight of Liver (mg Fe/g) Decrease From Baseline in Liver Iron Concentration (LIC) at Week 53(Week 53)