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
A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
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).
Exclusion Criteria:
Oral administration of once daily IMR-687
Drug: IMR-687
Oral administration of once daily IMR-687
Drug: IMR-687
Oral administration of once daily placebo
Drug: Placebo
Oral administration of once daily IMR-687
Oral administration of once daily Placebo
IMR-687 Safety and Tolerability
Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
Time frame: Baseline to Week 40
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
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
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
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
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
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
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
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
| Milestone | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|---|---|---|
| Started | 29 | 25 | 20 | 24 | 12 | 12 |
| Completed | 18 | 16 | 16 | 10 | 8 | 6 |
| Not completed | 11 | 9 | 4 | 14 | 4 | 6 |
Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
| Participants | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|---|---|---|
| Treatment emergent Adverse Events | 25 | 22 | 15 | 18 | 12 | 6 |
| Treatment emergent Adverse Event related to study drug | 19 | 15 | 8 | 11 | 7 | 4 |
| Grade 3 or greater treatment emergent Adverse Event | 4 | 9 | 2 | 4 | 1 | 1 |
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)
| Participants | TDT High Dose | TDT Low Dose | TDT Placebo |
|---|---|---|---|
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24 | 2 | 1 | 2 |
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.
| Participants | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|
| NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions. | 0 | 0 | 0 |
Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions
| Participants | NTDT High Dose | NTDT Low Dose | NTDT 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 Transfusions | 1 | 1 | 0 |
Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
| Participants | TDT High Dose | TDT Low Dose | TDT Placebo |
|---|---|---|---|
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36 | 0 | 1 | 1 |
Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
| Participants | TDT High Dose | TDT Low Dose | TDT Placebo |
|---|---|---|---|
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24 | 0 | 0 | 2 |
Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
| Participants | TDT High Dose | TDT Low Dose | TDT Placebo |
|---|---|---|---|
| TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36 | 0 | 1 | 1 |
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.
| Participants | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|
| NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions | 1 | 1 | 0 |
Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions
| Participants | NTDT High Dose | NTDT Low Dose | NTDT 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 Transfusions | 1 | 0 | 0 |
Collected over 10 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TDT High Dose | 0/29 (0%) | 1/29 (3.4%) | 25/29 (86.2%) |
| TDT Low Dose | 0/25 (0%) | 3/25 (12%) | 22/25 (88%) |
| TDT Placebo | 0/20 (0%) | 1/20 (5%) | 15/20 (75%) |
| NTDT High Dose | 0/24 (0%) | 3/24 (12.5%) | 18/24 (75%) |
| NTDT Low Dose | 0/12 (0%) | 0/12 (0%) | 12/12 (100%) |
| NTDT Placebo | 0/12 (0%) | 0/12 (0%) | 6/12 (50%) |
| Event | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|---|---|---|
| COVID19Infections and infestations | 0/29 | 2/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| Carbon Monoxide PoisoningInjury, poisoning and procedural complications | 0/29 | 0/25 | 1/20 | 0/24 | 0/12 | 0/12 |
| Lower Respiratory Tract InfectionInfections and infestations | 0/29 | 0/25 | 0/20 | 1/24 | 0/12 | 0/12 |
| Lower Limb FractureInjury, poisoning and procedural complications | 0/29 | 0/25 | 0/20 | 1/24 | 0/12 | 0/12 |
| CholelithiasisHepatobiliary disorders | 0/29 | 0/25 | 0/20 | 1/24 | 0/12 | 0/12 |
| Liver abscessInfections and infestations | 0/29 | 1/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| PneumoniaInfections and infestations | 0/29 | 1/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| Back PainMusculoskeletal and connective tissue disorders | 1/29 | 0/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| RashSkin and subcutaneous tissue disorders | 1/29 | 0/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| Transfusion ReactionInjury, poisoning and procedural complications | 1/29 | 0/25 | 0/20 | 0/24 | 0/12 | 0/12 |
| Event | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo |
|---|---|---|---|---|---|---|
| HeadacheNervous system disorders | 10/29 | 10/25 | 7/20 | 5/24 | 2/12 | 2/12 |
| NauseaGastrointestinal disorders | 11/29 | 6/25 | 1/20 | 5/24 | 1/12 | 1/12 |
| Abdominal Pain UpperGastrointestinal disorders | 2/29 | 1/25 | 1/20 | 3/24 | 3/12 | 0/12 |
| DizzinessNervous system disorders | 5/29 | 5/25 | 2/20 | 1/24 | 0/12 | 1/12 |
| DiarrhoeaGastrointestinal disorders | 4/29 | 1/25 | 2/20 | 1/24 | 2/12 | 0/12 |
| FatigueGeneral disorders | 1/29 | 0/25 | 0/20 | 3/24 | 2/12 | 0/12 |
| VomittingGastrointestinal disorders | 1/29 | 0/25 | 0/20 | 3/24 | 2/12 | 0/12 |
| AnemiaBlood and lymphatic system disorders | 0/29 | 1/25 | 1/20 | 2/24 | 2/12 | 1/12 |
| COVID19Infections and infestations | 1/29 | 3/25 | 0/20 | 3/24 | 0/12 | 2/12 |
| GastroenteritisInfections and infestations | 3/29 | 0/25 | 0/20 | 0/24 | 0/12 | 0/12 |
Safety Analysis Set
| Age, Continuous(Years) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| Mean | 31.7 ± 12.06 | 30.0 ± 9.95 | 31.3 ± 8.57 | 34.1 ± 12.64 | 28.5 ± 8.21 | 36.0 ± 9.56 | 31.9 ± 10.69 |
| Sex: Female, Male(Participants) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| Female | 15 | 15 | 9 | 10 | 6 | 8 | 63 |
| Male | 14 | 10 | 11 | 14 | 6 | 4 | 59 |
| Race (NIH/OMB)(Participants) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 5 | 7 | 4 | 4 | 3 | 4 | 27 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 0 | 0 | 1 | 0 | 2 |
| White | 19 | 17 | 14 | 17 | 7 | 6 | 80 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 1 | 2 | 3 | 1 | 2 | 13 |
| Region of Enrollment(Participants) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| United Kingdom | 1 | 0 | 0 | 2 | 0 | 1 | 4 |
| Malaysia | 4 | 6 | 4 | 3 | 3 | 2 | 22 |
| Greece | 9 | 2 | 1 | 5 | 0 | 2 | 19 |
| Lebanon | 0 | 4 | 3 | 0 | 1 | 0 | 8 |
| Netherlands | 0 | 0 | 0 | 2 | 0 | 1 | 3 |
| Turkey | 3 | 5 | 7 | 1 | 0 | 0 | 16 |
| Morocco | 1 | 1 | 0 | 2 | 0 | 2 | 6 |
| Denmark | 3 | 0 | 2 | 0 | 0 | 0 | 5 |
| Italy | 0 | 0 | 0 | 0 | 1 | 1 | 2 |
| Georgia | 0 | 2 | 1 | 3 | 1 | 1 | 8 |
| Israel | 2 | 2 | 2 | 1 | 0 | 0 | 7 |
| France | 2 | 1 | 0 | 0 | 2 | 2 | 7 |
| Tunisia | 4 | 2 | 0 | 5 | 4 | 0 | 15 |
| BMI(kg/m2) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| Mean | 22.900 ± 3.2252 | 21.252 ± 2.2874 | 22.699 ± 2.9968 | 22.031 ± 3.5415 | 21.1320 ± 3.5047 | 21.9120 ± 3.5638 | 22.0873 ± 3.1573 |
| Serum Ferritin(micrograms per liter) | TDT High Dose | TDT Low Dose | TDT Placebo | NTDT High Dose | NTDT Low Dose | NTDT Placebo | Total |
|---|---|---|---|---|---|---|---|
| Mean | 1724.4 ± 1857.66 | 3449.1 ± 5093.24 | 1793.3 ± 1844.72 | 981.4 ± 951.29 | 945.8 ± 962.09 | 447.8 ± 222.32 | 1726.69 ± 2740.18 |
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Cardurion Pharmaceuticals, Inc.