Back to resultsA Study of IMR-687 in Subjects With Beta Thalassemia
Primary Purpose
β Thalassemia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IMR-687
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for β Thalassemia focused on measuring Transfusion, TDT, NTDT
Eligibility Criteria
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
Sites / Locations
- Herlev Hospital
- Institut Universitaire du Cancer de Toulouse Oncopole
- Hôpital Edouard Herriot
- Hôpital Necker-Enfants Malades
- M. Zodelava Hematology Centre
- National Center of Surgery
- Medinvest - Institute of Hematology and Transfusiology
- Aghia Sofia General Children's Hospital
- Laiko General Hospital of Athens
- Ippokrateio General Hospital of Thessaloniki
- University General Hospital of Patras
- Rambam Health Care Campus
- Hadassah University Hospital Ein Kerem
- The Galilee Medical Center
- Emek Medical Center
- Azienda Ospedaliera Giuseppe Brotzu
- Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
- Chronic Care Center
- Hospital Sultanah Aminah Johor Bharu
- Hospital Sultanah Bahiyah
- Hospital Pulau Pinang
- Hospital Raja Permaisuri Bainun
- Hospital Queen Elizabeth - Kota Kinabalu
- Hospital Umum Sarawak
- Hôpital d'Enfants Rabat
- Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
- Centre Hôpital Universitaire Farhat Hached
- Centre National de Greffe de la Moelle Osseuse
- Hospital Aziza Othmana
- Akdeniz Üniversitesi
- Mersin Üniversitesi Tıp Fakültesi
- Hacettepe Üniversitesi
- Ege Universitesi Tip Fakultesi
- Whittington Health NHS Trust
- University College London Hospitals NHS Foundation Trust
- Manchester University NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Lower Dose IMR-687
Higher dose IMR-687
Placebo
Arm Description
Oral administration of once daily IMR-687
Oral administration of once daily IMR-687
Oral administration of once daily placebo
Outcomes
Primary Outcome Measures
IMR-687 Safety and Tolerability
Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
Secondary Outcome Measures
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)
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.
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
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)
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)
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)
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04411082
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
IMR-BTL-201demonstrated that while IMR-687 was generally well-tolerated, it failed to show any meaningful benefit in transfusion burden or improvement in most disease-related biomarkers. So, the sponsor has decided to discontinue this study
Study Start Date
October 16, 2020 (Actual)
Primary Completion Date
March 11, 2022 (Actual)
Study Completion Date
May 4, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imara, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
β Thalassemia
Keywords
Transfusion, TDT, NTDT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Double-Blind
Allocation
Randomized
Enrollment
122 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lower Dose IMR-687
Arm Type
Experimental
Arm Description
Oral administration of once daily IMR-687
Arm Title
Higher dose IMR-687
Arm Type
Experimental
Arm Description
Oral administration of once daily IMR-687
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral administration of once daily placebo
Intervention Type
Drug
Intervention Name(s)
IMR-687
Intervention Description
Oral administration of once daily IMR-687
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration of once daily Placebo
Primary Outcome Measure Information:
Title
IMR-687 Safety and Tolerability
Description
Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
Time Frame
Baseline to Week 40
Secondary Outcome Measure Information:
Title
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24
Description
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)
Time Frame
Baseline to Week 24
Title
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.
Description
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.
Time Frame
Baseline to Week 24
Title
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
Description
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
Title
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36
Description
Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
Time Frame
Baseline to Week 36
Title
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24
Description
Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
Time Frame
Baseline to Week 24
Title
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36
Description
Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
Time Frame
Baseline to Week 36
Title
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions
Description
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.
Time Frame
Baseline to Week 36
Title
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
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Luperchio
Organizational Affiliation
Cardurion Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Herlev Hospital
City
Herlev
State/Province
Hovedstaden
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Institut Universitaire du Cancer de Toulouse Oncopole
City
Toulouse cedex 9
State/Province
Haute-Garonn
ZIP/Postal Code
31059
Country
France
Facility Name
Hôpital Edouard Herriot
City
Lyon Cedex 03
State/Province
Rhone
ZIP/Postal Code
69437
Country
France
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
M. Zodelava Hematology Centre
City
Tbilisi
State/Province
Borjomi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
National Center of Surgery
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Medinvest - Institute of Hematology and Transfusiology
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
Facility Name
Aghia Sofia General Children's Hospital
City
Athens
State/Province
Attica
ZIP/Postal Code
11527
Country
Greece
Facility Name
Laiko General Hospital of Athens
City
Athens
State/Province
Attica
ZIP/Postal Code
11527
Country
Greece
Facility Name
Ippokrateio General Hospital of Thessaloniki
City
Thessaloníki
State/Province
Central Macedonia
ZIP/Postal Code
54642
Country
Greece
Facility Name
University General Hospital of Patras
City
Patra
State/Province
Peloponnese
ZIP/Postal Code
26504
Country
Greece
Facility Name
Rambam Health Care Campus
City
Haifa
State/Province
Haifa District
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Hadassah University Hospital Ein Kerem
City
Jerusalem
State/Province
Jerusalem District
ZIP/Postal Code
9112001
Country
Israel
Facility Name
The Galilee Medical Center
City
Nahariya
State/Province
Northern District
ZIP/Postal Code
2210001
Country
Israel
Facility Name
Emek Medical Center
City
Afula
ZIP/Postal Code
18101
Country
Israel
Facility Name
Azienda Ospedaliera Giuseppe Brotzu
City
Orbassano
State/Province
Turin
ZIP/Postal Code
10043
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
City
Orbassano
State/Province
Turin
ZIP/Postal Code
10043
Country
Italy
Facility Name
Chronic Care Center
City
Hazmiyeh
ZIP/Postal Code
213
Country
Lebanon
Facility Name
Hospital Sultanah Aminah Johor Bharu
City
Johor Bahru
State/Province
Johor
ZIP/Postal Code
80100
Country
Malaysia
Facility Name
Hospital Sultanah Bahiyah
City
Alor Setar
State/Province
Kedah
ZIP/Postal Code
05460
Country
Malaysia
Facility Name
Hospital Pulau Pinang
City
George Town
State/Province
Penang
ZIP/Postal Code
10450
Country
Malaysia
Facility Name
Hospital Raja Permaisuri Bainun
City
Ipoh
State/Province
Perak
ZIP/Postal Code
30450
Country
Malaysia
Facility Name
Hospital Queen Elizabeth - Kota Kinabalu
City
Kota Kinabalu
State/Province
Sabah
ZIP/Postal Code
88586
Country
Malaysia
Facility Name
Hospital Umum Sarawak
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Hôpital d'Enfants Rabat
City
Rabat
ZIP/Postal Code
10100
Country
Morocco
Facility Name
Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
City
Amsterdam
State/Province
North Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Centre Hôpital Universitaire Farhat Hached
City
Sousse
ZIP/Postal Code
4000
Country
Tunisia
Facility Name
Centre National de Greffe de la Moelle Osseuse
City
Tunis
ZIP/Postal Code
1006
Country
Tunisia
Facility Name
Hospital Aziza Othmana
City
Tunis
ZIP/Postal Code
1008
Country
Tunisia
Facility Name
Akdeniz Üniversitesi
City
Mersin
State/Province
Icel
ZIP/Postal Code
33110
Country
Turkey
Facility Name
Mersin Üniversitesi Tıp Fakültesi
City
Mersin
State/Province
Icel
ZIP/Postal Code
33110
Country
Turkey
Facility Name
Hacettepe Üniversitesi
City
Ankara
ZIP/Postal Code
06230
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Whittington Health NHS Trust
City
London
State/Province
England
ZIP/Postal Code
N19 5NF
Country
United Kingdom
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
State/Province
England
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Manchester University NHS Foundation Trust
City
Manchester
State/Province
England
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
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A Study of IMR-687 in Subjects With Beta Thalassemia
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