A Study of IMR-687 in Subjects With Beta Thalassemia

Overview

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

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 2022

Detailed Description

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) 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).

Interventions

  • Drug: IMR-687
    • Oral administration of once daily IMR-687
  • Drug: Placebo
    • Oral administration of once daily Placebo

Arms, Groups and Cohorts

  • Experimental: Lower Dose IMR-687
    • Oral administration of once daily IMR-687
  • Experimental: Higher dose IMR-687
    • Oral administration of once daily IMR-687
  • Placebo Comparator: Placebo
    • Oral administration of once daily placebo

Clinical Trial Outcome Measures

Primary Measures

  • Proportion of patients with adverse events and serious adverse events
    • Time Frame: Baseline to Week 40
    • Incidence of Adverse Events Incidence of Serious Adverse Events

Secondary Measures

  • TDT Patients: Reduction in red blood cell (RBC) transfusion burden
    • Time Frame: Week 12 through Week 36
    • Proportion of patients with ≥20% hematological improvement as compared to the 12 week prescreening timeframe Proportion of patients with ≥33% hematological improvement as compared to the 12 week prescreening timeframe
  • TDT Patients: Mean number of transfusion events
    • Time Frame: Baseline to Week 36, Weeks 24 to 36
    • a. Mean number of transfusion events
  • TDT Patients: Mean change in ICT dose and Serum ferritin levels
    • Time Frame: Baseline to Week 36, Weeks 24 to 36
    • a. Mean change in ICT dose and Serum ferritin levels
  • TDT Patients: Proportion of patients that had a decrease in ICT and serum ferritin as compared to the 12 week prescreening timeframe
    • Time Frame: Baseline to Week 36, Weeks 24 to 36
    • a. Proportion of patients that had a decrease in ICT and serum ferritin as compared to the 12 week prescreening timeframe
  • NTDT Patients:Mean change in HbF
    • Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36
    • a. Mean change in HbF
  • NTDT Patients: Mean change in percent HbF
    • Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36
    • a. Mean change in percent HbF
  • NTDT Patients: Mean change in HbF over a continuous 12-week interval in the absence of a transfusion
    • Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36
    • a. Mean change in HbF over a continuous 12-week interval in the absence of a transfusion
  • NTDT Patients: Subject Response in HbF (increase of ≥3%)
    • Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36
    • a. Subject Response in HbF (increase of ≥3%)
  • NTDT Patients: Mean change in Hb
    • Time Frame: Baseline to Week 12 to 24, Week 24 to 36
    • a. Mean change in Hb
  • NTDT Patients: Mean change in Hb over a continuous 12-week interval in the absence of a transfusion
    • Time Frame: Baseline to Week 12 to 24, Week 24 to 36
    • a. Mean change in Hb over a continuous 12-week interval in the absence of a transfusion
  • TDT and NTDT Patients: PK Parameter Cmax
    • Time Frame: Baseline to Week 36
    • a. Peak Plasma Concentration (Cmax)
  • TDT and NTDT Patients: PK Parameter Area Under the Plasma Concentration versus Time Curve (AUC)
    • Time Frame: Baseline to Week 36
    • a. Area Under the Plasma Concentration versus Time Curve (AUC)
  • TDT and NTDT Patients: PK Parameter Tmax
    • Time Frame: Baseline to Week 36
    • a. Time to maximum concentration (tmax)
  • TDT and NTDT Patients: PK Parameter t ½
    • Time Frame: Baseline to Week 36
    • a. Apparent terminal half-life t ½ (half-life)
  • TDT and NTDT Patients: PK Parameter AUC 0-24
    • Time Frame: Baseline to Week 36
    • a. Area Under the Plasma Concentration versus Time Curve (AUC) from time 0 to 24 hours
  • TDT and NTDT Patients: PK Parameter AUClast
    • Time Frame: Baseline to Week 36
    • a. 0 to the last measurable timepoint (AUClast)
  • TDT and NTDT Patients: PK Parameter AUC 0-infinity
    • Time Frame: Baseline to Week 36
    • a. Extrapolated to infinity (AUC0-∞)

Participating in This Clinical Trial

Inclusion Criteria

1. Documented diagnosis of β-thalassemia or HbE/ β-thalassemia. Concomitant single alpha gene deletion, duplication, or triplication is allowed.

2. Documentation of dates of transfusions and the number of all RBC units within the 12 weeks prior to Screening.

3. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.

4. ECOG performance score of 0-1

5. Female subjects must not be pregnant, not be breast feeding, and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.

Exclusion Criteria

1. Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β thalassemia.

2. Body mass index (BMI) <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2

3. 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).

4. Stroke requiring medical intervention ≤24 weeks prior to randomization.

5. Platelet count >1000 × 109/L.

6. Subjects on iron chelation therapy (ICT) at the time of ICF signing must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date.

7. Prior exposure to sotatercept, luspatercept, IMR-687, or gene therapy.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Imara, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Omkar Marathe, MD, Principal Investigator, The Oncology Institute Long Beach
  • Overall Contact(s)
    • Eleanor Lisbon, MD, MPH, 913-449-4319, elisbon@imaratx.com

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