A Study of IMR-687 in Subjects With Beta Thalassemia

Study Overview
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Brief Summary
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A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia

Detailed Description
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A phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of IMR-687 (phosphodiesterase (PDE) 9 inhibitor) administered once daily (qd) orally for 36 weeks in 2 populations of adult subjects with β-thalassemia: Population 1 (Transfusion Dependent Thalassemia (TDT) subjects) and Population 2 (Non-Transfusion Dependent Thalassemia (NTDT) subjects).

Official Title
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A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia

Conditions
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β Thalassemia

Intervention / Treatment
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* Drug: IMR-687
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history. Concomitant alpha gene deletion, duplication, or triplication is allowed. Documentation of the dates of transfusion events and the number of all pRBC units per event within the 12 weeks prior to the Baseline (Day 1) visit. . Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff. TDT Subjects: subjects must be regularly transfused, defined as >3 to 10 pRBC units in the12 weeks prior to Baseline (Day 1) visit and no transfusion-free period for >35 days during that period. NTDT subjects: Subjects must be transfusion independent, defined as 0 to ≤3 units of pRBCs received during the 12-week period prior to the Baseline (Day 1) visit, must not be on a regular transfusion program, must be RBC transfusion-free for at least ≥ 4 weeks prior to randomization, and must not be scheduled to start a regular hematopoietic stem cell transplantation within 9 months. NTDT subjects: Subjects must have Hb ≤10.0 g/dL at Screening; the screening Hb sample must be collected 7 to 28 days prior to randomization. Hb values within 21 days post-transfusion will be excluded. ECOG performance score of 0 to 1 Female subjects must not be pregnant, or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner. Exclusion Criteria: Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β thalassemia. Body mass index (BMI) <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2 Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or acute event of malaria, or who are known to be positive for human immunodeficiency virus (HIV). Stroke requiring medical intervention ≤24 weeks prior to randomization. Platelet count >1000 × 109/L. Participated in another clinical study of an investigational agent (or device) within 30 days or 5-half-lives of date of informed consent, whichever is longer, or is currently participating in another study. For Subjects on iron chelation therapy (ICT) at the time of ICF signing, initiation of ICT less than 24 weeks before the predicted randomization date. Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6 months prior to randomization (Day 1). Subjects who have major organ damage

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower Dose IMR-687<br>Oral administration of once daily IMR-687 | Drug: IMR-687<br>* Oral administration of once daily IMR-687<br>|
| Experimental: Higher dose IMR-687<br>Oral administration of once daily IMR-687 | Drug: IMR-687<br>* Oral administration of once daily IMR-687<br>|
| Placebo Comparator: Placebo<br>Oral administration of once daily placebo | Drug: Placebo<br>* Oral administration of once daily Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IMR-687 Safety and Tolerability | Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events | Baseline to Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24 | Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1) | Baseline to Week 24 | 
| NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions. | Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions. | Baseline to Week 24 | 
| NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions | Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions | Baseline to Week 24 | 
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36 | Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1) | Baseline to Week 36 | 
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24 | Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1) | Baseline to Week 24 | 
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36 | Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1) | Baseline to Week 36 | 
| NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions | Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions. | Baseline to Week 36 | 
| NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions | Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions | Baseline to Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transfusion, TDT, NTDT