A Study of IMR-687 in Subjects With Sickle Cell Disease

Phase 2

Terminated

• Conditions: Sickle Cell Disease
• Interventions: Drug: IMR-687; Drug: Placebo

• Registration Number: NCT04474314
• Lead Sponsor: Cardurion Pharmaceuticals, Inc.

Brief Summary

A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease

Detailed Description

A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with sickle cell disease (SCD; homozygous sickle hemoglobin \[HbSS\], sickle-β0 \[HbSβ0\] thalassemia, or sickle-β+ \[HbSβ+\] thalassemia) to evaluate the safety and efficacy of the phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52 weeks.

Study Timeline

• Study First Submitted: 2020-06-26
• Study First Submitted QC: 2020-07-15
• Study First Posted: 2020-07-16
• Study Start: 2020-08-13
• Primary Completion: 2022-03-02
• Study Completion: 2022-05-04
• Results First Submitted: 2022-06-08
• Results First Submitted QC: 2023-10-17
• Results First Posted: 2023-10-18
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 115

Inclusion Criteria

1. Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)
2. Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.
3. Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in the past 12 months at the time of informed consent signing and at randomization (Day 1).
4. Subjects receiving HU must have received it continuously for at least 6 months prior to signing informed consent, and must have been on a stable dose for at least 3 months prior to signing the informed consent, with no anticipated need for dose adjustments during the study including the screening period, in the opinion of the investigator.
5. Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
6. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.

Exclusion Criteria

1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
2. Subjects participating in a chronic/prophylactic RBC transfusion program (i.e., regularly scheduled RBC transfusions); any transfusions within 21 days of screening or baseline Hb measurements
3. Subjects with HbF >25% at screening.
4. Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase >3x upper limit of normal.
5. Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a BMI >35 kg/m2.
6. 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).
7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).
8. Prior exposure to IMR-687.
9. Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least 28 days prior to randomization (Day 1).
10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
11. Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth factor treatment within 3 months of signing the ICF or anticipated need for such agents during the study.
12. Prior gene therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lower Dose IMR-687	IMR-687	Oral administration of once daily IMR-687
Placebo	Placebo	Oral administration of once daily Placebo
Higher dose IMR-687	IMR-687	Oral administration of once daily IMR-687

Primary Outcome Measures

Name	Time	Method
Effect on the Incidence of Vaso-occlusive Crises (VOCs)	Baseline to Week 52	Annualized rate of VOCs. For each subject, the total number of VOCs on treatment were divided by the time on treatment divided by 52 weeks. The median was then summarized.
Proportion of Patients With Adverse Events and Serious Adverse Events	Baseline to Week 56	Incidence of Adverse Events Incidence of Serious Adverse Events

Trial Locations

Locations (49)

University of Alabama at Birmingham School of Medicine - 1917 Clinic; 🇺🇸 Birmingham, Alabama, United States

Arkansas Primary Care Clinic; 🇺🇸 Little Rock, Arkansas, United States

University of California San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Center For Inherited Blood Disorders; 🇺🇸 Santa Ana, California, United States

The Oncology Institute Long Beach; 🇺🇸 Whittier, California, United States

University of Connecticut Health Main Building; 🇺🇸 Farmington, Connecticut, United States

Children's Healthcare of Atlanta; 🇺🇸 Atlanta, Georgia, United States

The University of Illinois at Chicago College of Medicine; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States

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