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TerminatedNCT04411082Updated May 15, 2025Results posted

A Study of IMR-687 in Subjects With Beta Thalassemia

A Phase 2 interventional study of IMR-687 and Placebo in β Thalassemia, sponsored by Cardurion Pharmaceuticals, Inc.. Terminated at 36 sites in 13 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-05-15.

Sponsored by Cardurion Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment

Why this study was terminated
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
Phase
Phase 2
Study type
Interventional
Enrollment
122
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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

Read the 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).

02

Conditions studied

  • β Thalassemia

Keywords

  • Transfusion
  • TDT
  • NTDT
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
122 participants (actual)

Study arms

  • Experimental
    Lower Dose IMR-687

    Oral administration of once daily IMR-687

    Drug: IMR-687

  • Experimental
    Higher dose IMR-687

    Oral administration of once daily IMR-687

    Drug: IMR-687

  • Placebo comparator
    Placebo

    Oral administration of once daily placebo

    Drug: Placebo

Interventions

  • DrugIMR-687

    Oral administration of once daily IMR-687

  • DrugPlacebo

    Oral administration of once daily Placebo

05

What researchers measure

Primary outcomes

  1. IMR-687 Safety and Tolerability

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

    Time frame: Baseline to Week 40

Secondary outcomes

  1. 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)

    Time frame: Baseline to Week 24

  2. 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.

    Time frame: Baseline to Week 24

  3. 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

    Time frame: Baseline to Week 24

  4. 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)

    Time frame: Baseline to Week 36

  5. 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)

    Time frame: Baseline to Week 24

  6. 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)

    Time frame: Baseline to Week 36

  7. 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.

    Time frame: Baseline to Week 36

  8. 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

    Time frame: Baseline to Week 36

06

Results

Posted Jun 30, 2022

Participant flow

Participant flow — Overall Study
MilestoneTDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT Placebo
Started292520241212
Completed1816161086
Not completed11941446

Outcome measures

PrimaryIMR-687 Safety and Tolerability

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

Time frame:
Baseline to Week 40
Reported as:
Count of participants · Participants
IMR-687 Safety and Tolerability
ParticipantsTDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT Placebo
Treatment emergent Adverse Events25221518126
Treatment emergent Adverse Event related to study drug191581174
Grade 3 or greater treatment emergent Adverse Event492411
SecondaryTDT 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)

Time frame:
Baseline to Week 24
Reported as:
Count of participants · Participants
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24
ParticipantsTDT High DoseTDT Low DoseTDT Placebo
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24212
Statistical analysis
  • TDT High Dose vs TDT Low Dose vs TDT Placebo · Fisher Exact · p = >0.99
SecondaryNTDT 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.

Time frame:
Baseline to Week 24
Reported as:
Count of participants · Participants
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.
ParticipantsNTDT High DoseNTDT Low DoseNTDT Placebo
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.000
Statistical analysis
  • NTDT High Dose vs NTDT Low Dose vs NTDT Placebo · Fisher Exact · p = >0.99
SecondaryNTDT 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

Time frame:
Baseline to Week 24
Reported as:
Count of participants · Participants
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
ParticipantsNTDT High DoseNTDT Low DoseNTDT Placebo
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 Transfusions110
Statistical analysis
  • NTDT High Dose vs NTDT Low Dose vs NTDT Placebo · Fisher Exact · p = >0.99
SecondaryTDT 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)

Time frame:
Baseline to Week 36
Reported as:
Count of participants · Participants
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36
ParticipantsTDT High DoseTDT Low DoseTDT Placebo
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36011
Statistical analysis
  • TDT High Dose vs TDT Low Dose vs TDT Placebo · Fisher Exact · p = >0.4839
SecondaryTDT 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)

Time frame:
Baseline to Week 24
Reported as:
Count of participants · Participants
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24
ParticipantsTDT High DoseTDT Low DoseTDT Placebo
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24002
Statistical analysis
  • TDT High Dose vs TDT Low Dose vs TDT Placebo · Fisher Exact · p = 0.2065
SecondaryTDT 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)

Time frame:
Baseline to Week 36
Reported as:
Count of participants · Participants
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36
ParticipantsTDT High DoseTDT Low DoseTDT Placebo
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36011
Statistical analysis
  • TDT High Dose vs TDT Low Dose vs TDT Placebo · Fisher Exact · p = 0.4839
SecondaryNTDT 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.

Time frame:
Baseline to Week 36
Reported as:
Count of participants · Participants
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions
ParticipantsNTDT High DoseNTDT Low DoseNTDT Placebo
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions110
Statistical analysis
  • NTDT High Dose vs NTDT Low Dose vs NTDT Placebo · Fisher Exact · p = >0.99
SecondaryNTDT: 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

Time frame:
Baseline to Week 36
Reported as:
Count of participants · Participants
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
ParticipantsNTDT High DoseNTDT Low DoseNTDT Placebo
NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions100
Statistical analysis
  • NTDT High Dose vs NTDT Low Dose vs NTDT Placebo · Fisher Exact · p = >0.99

Adverse events

Collected over 10 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TDT High Dose0/29 (0%)1/29 (3.4%)25/29 (86.2%)
TDT Low Dose0/25 (0%)3/25 (12%)22/25 (88%)
TDT Placebo0/20 (0%)1/20 (5%)15/20 (75%)
NTDT High Dose0/24 (0%)3/24 (12.5%)18/24 (75%)
NTDT Low Dose0/12 (0%)0/12 (0%)12/12 (100%)
NTDT Placebo0/12 (0%)0/12 (0%)6/12 (50%)
Most frequent serious events
Most frequent serious events
EventTDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT Placebo
COVID19Infections and infestations0/292/250/200/240/120/12
Carbon Monoxide PoisoningInjury, poisoning and procedural complications0/290/251/200/240/120/12
Lower Respiratory Tract InfectionInfections and infestations0/290/250/201/240/120/12
Lower Limb FractureInjury, poisoning and procedural complications0/290/250/201/240/120/12
CholelithiasisHepatobiliary disorders0/290/250/201/240/120/12
Liver abscessInfections and infestations0/291/250/200/240/120/12
PneumoniaInfections and infestations0/291/250/200/240/120/12
Back PainMusculoskeletal and connective tissue disorders1/290/250/200/240/120/12
RashSkin and subcutaneous tissue disorders1/290/250/200/240/120/12
Transfusion ReactionInjury, poisoning and procedural complications1/290/250/200/240/120/12
Most frequent other events
Showing 10 of 13
Most frequent other events
EventTDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT Placebo
HeadacheNervous system disorders10/2910/257/205/242/122/12
NauseaGastrointestinal disorders11/296/251/205/241/121/12
Abdominal Pain UpperGastrointestinal disorders2/291/251/203/243/120/12
DizzinessNervous system disorders5/295/252/201/240/121/12
DiarrhoeaGastrointestinal disorders4/291/252/201/242/120/12
FatigueGeneral disorders1/290/250/203/242/120/12
VomittingGastrointestinal disorders1/290/250/203/242/120/12
AnemiaBlood and lymphatic system disorders0/291/251/202/242/121/12
COVID19Infections and infestations1/293/250/203/240/122/12
GastroenteritisInfections and infestations3/290/250/200/240/120/12

Baseline characteristics

Safety Analysis Set

Age, Continuous
Age, Continuous(Years)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
Mean31.7 ± 12.0630.0 ± 9.9531.3 ± 8.5734.1 ± 12.6428.5 ± 8.2136.0 ± 9.5631.9 ± 10.69
Sex: Female, Male
Sex: Female, Male(Participants)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
Female15159106863
Male141011146459
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
American Indian or Alaska Native0000000
Asian57443427
Native Hawaiian or Other Pacific Islander0000000
Black or African American1000102
White191714177680
More than one race0000000
Unknown or Not Reported41231213
Region of Enrollment
Region of Enrollment(Participants)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
United Kingdom1002014
Malaysia46433222
Greece92150219
Lebanon0430108
Netherlands0002013
Turkey35710016
Morocco1102026
Denmark3020005
Italy0000112
Georgia0213118
Israel2221007
France2100227
Tunisia42054015
BMI
BMI(kg/m2)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
Mean22.900 ± 3.225221.252 ± 2.287422.699 ± 2.996822.031 ± 3.541521.1320 ± 3.504721.9120 ± 3.563822.0873 ± 3.1573
Serum Ferritin
Serum Ferritin(micrograms per liter)TDT High DoseTDT Low DoseTDT PlaceboNTDT High DoseNTDT Low DoseNTDT PlaceboTotal
Mean1724.4 ± 1857.663449.1 ± 5093.241793.3 ± 1844.72981.4 ± 951.29945.8 ± 962.09447.8 ± 222.321726.69 ± 2740.18
07

Study locations

36 sites
  • Herlev Hospital
    Herlev, Hovedstaden 2730, Denmark
  • Institut Universitaire du Cancer de Toulouse Oncopole
    Toulouse cedex 9, Haute-Garonn 31059, France
  • Hôpital Edouard Herriot
    Lyon Cedex 03, Rhone 69437, France
  • Hôpital Necker-Enfants Malades
    Paris, 75015, France
  • M. Zodelava Hematology Centre
    Tbilisi, Borjomi 0112, Georgia
  • National Center of Surgery
    Tbilisi, 0159, Georgia
  • Medinvest - Institute of Hematology and Transfusiology
    Tbilisi, 0186, Georgia
  • Aghia Sofia General Children's Hospital
    Athens, Attica 11527, Greece
  • Laiko General Hospital of Athens
    Athens, Attica 11527, Greece
  • Ippokrateio General Hospital of Thessaloniki
    Thessaloníki, Central Macedonia 54642, Greece
  • University General Hospital of Patras
    Patra, Peloponnese 26504, Greece
  • Rambam Health Care Campus
    Haifa, Haifa District 3109601, Israel
  • Hadassah University Hospital Ein Kerem
    Jerusalem, Jerusalem District 9112001, Israel
  • The Galilee Medical Center
    Nahariya, Northern District 2210001, Israel
  • Emek Medical Center
    Afula, 18101, Israel
  • Azienda Ospedaliera Giuseppe Brotzu
    Orbassano, Turin 10043, Italy
  • Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
    Orbassano, Turin 10043, Italy
  • Chronic Care Center
    Hazmiyeh, 213, Lebanon
  • Hospital Sultanah Aminah Johor Bharu
    Johor Bahru, Johor 80100, Malaysia
  • Hospital Sultanah Bahiyah
    Alor Setar, Kedah 05460, Malaysia
  • Hospital Pulau Pinang
    George Town, Penang 10450, Malaysia
  • Hospital Raja Permaisuri Bainun
    Ipoh, Perak 30450, Malaysia
  • Hospital Queen Elizabeth - Kota Kinabalu
    Kota Kinabalu, Sabah 88586, Malaysia
  • Hospital Umum Sarawak
    Kuching, Sarawak 93586, Malaysia
  • Hôpital d'Enfants Rabat
    Rabat, 10100, Morocco
  • Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
    Amsterdam, North Holland 1105 AZ, Netherlands
  • Centre Hôpital Universitaire Farhat Hached
    Sousse, 4000, Tunisia
  • Centre National de Greffe de la Moelle Osseuse
    Tunis, 1006, Tunisia
  • Hospital Aziza Othmana
    Tunis, 1008, Tunisia
  • Akdeniz Üniversitesi
    Mersin, Icel 33110, Turkey
  • Mersin Üniversitesi Tıp Fakültesi
    Mersin, Icel 33110, Turkey
  • Hacettepe Üniversitesi
    Ankara, 06230, Turkey
  • Ege Universitesi Tip Fakultesi
    Izmir, 35100, Turkey
  • Whittington Health NHS Trust
    London, England N19 5NF, United Kingdom
  • University College London Hospitals NHS Foundation Trust
    London, England NW1 2PG, United Kingdom
  • Manchester University NHS Foundation Trust
    Manchester, England M13 9WL, United Kingdom
08

References and documents

Study documents

  • Study protocol · Mar 15, 2021
  • Statistical analysis plan · Oct 14, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04411082
Lead sponsor
Cardurion Pharmaceuticals, Inc.
Collaborators
Imara, Inc.
Responsible party
Sponsor
First posted
Jun 2, 2020
Start date
Oct 16, 2020
Primary completion
Mar 11, 2022
Completion
May 4, 2022
Results posted
Jun 30, 2022
Last update
May 15, 2025

Study contacts

Steve Luperchio
study director · Cardurion Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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