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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04411082
Other study ID # IMR-BTL-201
Secondary ID 2019-002989-12
Status Terminated
Phase Phase 2
First received
Last updated
Start date October 16, 2020
Est. completion date May 4, 2022

Study information

Verified date June 2022
Source Imara, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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).


Recruitment information / eligibility

Status Terminated
Enrollment 122
Est. completion date May 4, 2022
Est. primary completion date March 11, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: 1. Documented diagnosis of ß-thalassemia or HbE/ ß-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 a-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ ß 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

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Denmark Herlev Hospital Herlev Hovedstaden
France Hôpital Edouard Herriot Lyon Cedex 03 Rhone
France Hôpital Necker-Enfants Malades Paris
France Institut Universitaire du Cancer de Toulouse Oncopole Toulouse cedex 9 Haute-Garonn
Georgia M. Zodelava Hematology Centre Tbilisi Borjomi
Georgia Medinvest - Institute of Hematology and Transfusiology Tbilisi
Georgia National Center of Surgery Tbilisi
Greece Aghia Sofia General Children's Hospital Athens Attica
Greece Laiko General Hospital of Athens Athens Attica
Greece University General Hospital of Patras Patra Peloponnese
Greece Ippokrateio General Hospital of Thessaloniki Thessaloníki Central Macedonia
Israel Emek Medical Center Afula
Israel Rambam Health Care Campus Haifa Haifa District
Israel Hadassah University Hospital Ein Kerem Jerusalem Jerusalem District
Israel The Galilee Medical Center Nahariya Northern District
Italy Azienda Ospedaliera Giuseppe Brotzu Orbassano Turin
Italy Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli Orbassano Turin
Lebanon Chronic Care Center Hazmiyeh
Malaysia Hospital Sultanah Bahiyah Alor Setar Kedah
Malaysia Hospital Pulau Pinang George Town Penang
Malaysia Hospital Raja Permaisuri Bainun Ipoh Perak
Malaysia Hospital Sultanah Aminah Johor Bharu Johor Bahru Johor
Malaysia Hospital Queen Elizabeth - Kota Kinabalu Kota Kinabalu Sabah
Malaysia Hospital Umum Sarawak Kuching Sarawak
Morocco Hôpital d'Enfants Rabat Rabat
Netherlands Amsterdam Universitair Medische Centra - Academisch Medisch Centrum Amsterdam North Holland
Tunisia Centre Hôpital Universitaire Farhat Hached Sousse
Tunisia Centre National de Greffe de la Moelle Osseuse Tunis
Tunisia Hospital Aziza Othmana Tunis
Turkey Hacettepe Üniversitesi Ankara
Turkey Ege Universitesi Tip Fakultesi Izmir
Turkey Akdeniz Üniversitesi Mersin Icel
Turkey Mersin Üniversitesi Tip Fakültesi Mersin Icel
United Kingdom University College London Hospitals NHS Foundation Trust London England
United Kingdom Whittington Health NHS Trust London England
United Kingdom Manchester University NHS Foundation Trust Manchester England

Sponsors (1)

Lead Sponsor Collaborator
Imara, Inc.

Countries where clinical trial is conducted

Denmark,  France,  Georgia,  Greece,  Israel,  Italy,  Lebanon,  Malaysia,  Morocco,  Netherlands,  Tunisia,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary IMR-687 Safety and Tolerability Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events Baseline to Week 40
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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