Efficacy and Safety Study of Multiple Doses of VIT-2763 in Adults With Transfusion-dependent Beta-thalassemia

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763 as measured by the reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24, to identify the most efficacious and safe dose.

Detailed Description
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All patients giving written informed consent will undergo a 12-week screening period to determine eligibility for study entry. At Day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner to 1 of 4 treatment groups: VIT-2763 60 mg (once daily), 60 mg (twice daily), or 120 mg (twice daily) or placebo. The randomisation will be stratified (balanced allocation across treatment groups) according to β0/β0 genotype (yes/no). The duration of the treatment with VIT-2763 or placebo is 24 weeks, after which patients will undergo a 12-week post-treatment follow-up period.

Official Title
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A Phase 2b, Double-blind, Randomised, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of VIT-2763 Multiple Doses in Adults With Transfusion-dependent Beta-thalassaemia

Conditions
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Beta-Thalassemia

Intervention / Treatment
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* Drug: VIT-2763 60 mg QD
* Drug: VIT-2763 60 mg BID
* Drug: VIT-2763 120 mg BID
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight ≥40.0 kg and ≤100 kg at screening Documented diagnosis of beta-thalassemia or Hb E/beta-thalassemia Red blood cell (RBC) transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomization and no transfusion-free period for ≥35 days during that period Ability to understand the requirements of the study and provide written informed consent Exclusion Criteria: Documented diagnosis of Hb S/beta-thalassemia, alpha-thalassemia, or delta beta (δβ)-thalassemia, or hereditary persistence of foetal Hb. History of partial or total splenectomy within 4 months prior to screening. History of myocardial iron overload Chronic liver disease or history of liver cirrhosis Clinically relevant renal disease History or clinically important finding of cardiac disorders History of clinically significant lung disease Uncontrolled hypertension (> Grade 1 according to NCI CTCAE current version) Unable to take and absorb oral medications. Pregnancy or breastfeeding History of drug or alcohol abuse within 2 years prior to screening History or concomitant solid tumors and/or hematological malignancies unless resolved in the ≥5 past years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIT-2763 60 mg QD<br>VIT-2763 60 mg administered once daily | Drug: VIT-2763 60 mg QD<br>* Participants receive one VIT-2763 60 mg capsule plus one Placebo capsule orally in the morning, and 2 Placebo capsules orally in the evening, for 24 weeks.<br>* Other names: Vamifeport 60 mg QD;|
| Experimental: VIT-2763 60 mg BID<br>VIT-2763 60 mg administered twice daily | Drug: VIT-2763 60 mg BID<br>* Participants receive one VIT-2763 60 mg capsule plus one Placebo capsule orally, twice daily for 24 weeks.<br>* Other names: Vamifeport 60 mg BID;|
| Experimental: VIT-2763 120 mg BID<br>VIT-2763 120 mg administered twice daily | Drug: VIT-2763 120 mg BID<br>* Participants receive two VIT-2763 60 mg capsules orally, twice daily for 24 weeks.<br>* Other names: Vamifeport 120 mg BID;|
| Placebo Comparator: Placebo<br>Placebo capsule administered twice daily | Drug: Placebo<br>* Participants receive two Placebo capsules matching VIT-2763 orally, twice daily for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving ≥33% reduction of RBC transfusions from baseline and a reduction of ≥2 units assessed consecutively from Week 13 to Week 24 compared to the baseline transfusion |  | Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in RBC transfusions over Weeks 13 to 24 compared to the baseline RBC transfusion burden derived using the last 12 weeks prior to randomization. |  | Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1) | 
| Proportion of patients achieving ≥50% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24. |  | Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1) | 
| Proportion of patients achieving ≥33% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24. |  | Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1) | 
| Mean change from baseline in Quality of Life (QoL) total score | Transfusion-dependent QoL Questionnaire (TranQuol): a disease-specific, validated, QoL measure developed for thalassemia patients. The adult version includes 36 questions grouped into 5 domains: physical health, emotional health, sexual health, family functioning, and school/career functioning. The total score ranges from 0 (worst) to 100 (best). | Week 15 and Week 24 comparing to Baseline (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-Thalassemia, Transfusion-dependent Thalassemia