A Study of IMR-687 in Subjects With Beta Thalassemia

• ClinicalTrials.gov Identifier: NCT04411082
• Recruitment Status: Terminated
• First Posted: June 2, 2020
• Results First Posted: June 30, 2022
• Last Update Posted: March 8, 2023
• Sponsor: Imara, Inc.
• Information provided by (Responsible Party): Imara, Inc.

Tracking Information

• First Submitted Date: April 15, 2020
• First Posted Date: June 2, 2020
• Results First Submitted Date: June 6, 2022
• Results First Posted Date: June 30, 2022
• Last Update Posted Date: March 8, 2023
• Actual Study Start Date: October 16, 2020
• Actual Primary Completion Date: March 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 6, 2022)

IMR-687 Safety and Tolerability [ Time Frame: Baseline to Week 40 ]

Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events

Original Primary Outcome Measures (submitted: May 27, 2020)

Proportion of patients with adverse events and serious adverse events [ Time Frame: Baseline to Week 40 ]

1. Incidence of Adverse Events
2. Incidence of Serious Adverse Events

Current Secondary Outcome Measures (submitted: June 6, 2022)

• TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24 [ Time Frame: Baseline 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)
• NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions. [ Time Frame: Baseline to Week 24 ]
  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.
• 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 [ Time Frame: Baseline to Week 24 ]
  Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions
• TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36 [ Time Frame: Baseline 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)
• TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24 [ Time Frame: Baseline 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)
• TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36 [ Time Frame: Baseline 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)
• NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions [ Time Frame: Baseline to Week 36 ]
  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.
• 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 [ Time Frame: Baseline to Week 36 ]
  Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions

Original Secondary Outcome Measures (submitted: May 27, 2020)

• TDT Patients: Reduction in red blood cell (RBC) transfusion burden [ Time Frame: Week 12 through Week 36 ]
  1. Proportion of patients with ≥20% hematological improvement as compared to the 12 week prescreening timeframe
  2. 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-∞)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of IMR-687 in Subjects With Beta Thalassemia
• Official Title: A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia
• Brief Summary: A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
• 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) 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).
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:

Double-Blind

Primary Purpose: Treatment

• Condition: β Thalassemia

Intervention

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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 9, 2022): 122
• Original Estimated Enrollment (submitted: May 27, 2020): 120
• Actual Study Completion Date: May 4, 2022
• Actual Primary Completion Date: March 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history. Concomitant alpha gene deletion, duplication, or triplication is allowed.
2. 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. .
3. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
4. 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.
5. 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
6. hematopoietic stem cell transplantation within 9 months.
7. 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.
8. ECOG performance score of 0 to 1
9. 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:

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. 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.
7. 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.
8. Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6 months prior to randomization (Day 1).
9. Subjects who have major organ damage

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, France, Georgia, Greece, Israel, Italy, Lebanon, Malaysia, Morocco, Netherlands, Tunisia, Turkey, United Kingdom
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT04411082
• Other Study ID Numbers: IMR-BTL-201; 2019-002989-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Imara, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Imara, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Steve Luperchio; Cardurion Pharmaceuticals

• PRS Account: Imara, Inc.
• Verification Date: June 2022