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

A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease

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

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: IMR-687; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ghana
  • Accra, Ghana, PO Box 77
    • Korle Bu Teaching Hospital
  • Kintampo, Ghana, Brong-Ahafo Region
    • Kintampo Health Research Centre
• Greece
  • Patra, Greece, 26504
    • University General Hospital of Patras
  • Thessaloníki, Greece, 54642
    • Ippokrateio General Hospital of Thessaloniki
  • Attica
    • Athens, Attica, Greece, 11526
      • Laiko General Hospital of Athens
• Italy
  • Genoa, Italy, 16128
    • Ente Ospedaliero Ospedali Galliera
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
  • Orbassano
    • Turin, Orbassano, Italy, 10043
      • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
  • Rome
    • Roma, Rome, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli
• Kenya
  • Nairobi, Kenya, 00100
    • Gertrude's Children's Hospital
  • Nairobi, Kenya, 00100
    • The Centre for Respiratory Diseases Research - Kenya Medical Research Institute
  • Nyanza
    • Kisumu, Nyanza, Kenya, 40100
      • Kenya Medical Research Institute - Kisumu
• Lebanon
  • Beirut, Lebanon, 01107 2020
    • American University of Beirut Medical Center
  • Hazmiyeh, Lebanon
    • Chronic Care Center
  • North Governorate
    • Tripoli, North Governorate, Lebanon
      • Hopital Nini
• Morocco
  • Rabat, Morocco, 10100
    • Hôpital d'Enfants Rabat
• Netherlands
  • South Holland
    • Den Haag, South Holland, Netherlands, 2545 AA
      • Hagaziekenhuis Van Den Haag - Leyweg
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• Senegal
  • Dakar, Senegal, 5002
    • Centre National De Transfusion Sanguine - Du Senegal
• Tunisia
  • Sfax, Tunisia, 3089
    • Hédi Chaker Hospital
  • Sousse, Tunisia, 4000
    • Centre Hôpital Universitaire Farhat Hached
  • Tunis, Tunisia, 1006
    • Centre National de Greffe de la Moelle Osseuse
  • Tunis, Tunisia, 1008
    • Hospital Aziza Othmana
• Uganda
  • Jinja, Uganda, PO Box 43
    • Jinja Regional Referral Hospital
  • Kampala, Uganda, PO Box 3935
    • Uganda Cancer Institute
  • Kampala, Uganda, PO Box 7072
    • Makerere University College of Health Sciences
  • Kampala, Uganda, Wskiso District
    • Joint Clinical Research Center - Lubowa
  • Tororo, Uganda, 256
    • Infectious Diseases Research Collaboration - Tororo
• United Kingdom
  • England
    • Bristol, England, United Kingdom, BS1 3NU
      • University Hospitals Bristol NHS Foundation Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
    • London, England, United Kingdom, SE1 9Rt
      • Guy's and Saint Thomas' NHS Foundation Trust
    • London, England, United Kingdom, NW1 2PG
      • University College London Hospitals NHS
    • Manchester, England, United Kingdom, M13 9WL
      • Manchester University NHS Foundation Trust
    • Oxford, England, United Kingdom, OX3 7LE
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham School of Medicine - 1917 Clinic
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Arkansas Primary Care Clinic
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • Santa Ana, California, United States, 92705
      • Center for Inherited Blood Disorders
    • Whittier, California, United States, 90603
      • The Oncology Institute Long Beach
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Main Building
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612-4333
      • The University of Illinois at Chicago College of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine - Center for Blood Disorders
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Medical Center-Temple
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Health - Ambulatory Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower Dose IMR-687; Oral administration of once daily IMR-687	Drug: IMR-687; Oral administration of once daily IMR-687
Experimental: Higher dose IMR-687; Oral administration of once daily IMR-687	Drug: IMR-687; Oral administration of once daily IMR-687
Placebo Comparator: Placebo; Oral administration of once daily Placebo	Drug: Placebo; Oral administration of once daily Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on the Incidence of Vaso-occlusive Crises (VOCs)	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.	Baseline to Week 52
Proportion of Patients With Adverse Events and Serious Adverse Events	Incidence of Adverse Events Incidence of Serious Adverse Events	Baseline to Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first vaso-occlusive crises (VOCs)	a. Time to first VOC	Baseline to Week 52
Proportion of HbF response	a. Proportion of Subject with response to HbF (absolute increase of ≥3%)	Baseline to Week 24
Proportion of VOC-free subject		Baseline to Week 52
Annualized rate of hospitalizations for vaso-occlusive crises (VOCs)	a. Annualized rate of hospitalizations for VOCs	Baseline to Week 24, and Week 52
Time to second vaso-occlusive crises (VOCs)	a. Time to second VOC	Baseline to Week 24, and Week 52
Proportion of HbF response	a. Proportion of Subject with response to HbF (absolute increase of ≥3%)	Baseline to Week 52
Change in HbF and F Cells	a. Change in HbF (%) and F-cells (%)	Baseline to Week 24, and Week 52
Proportion of Subject response in total Hb	a. Proportion of Subject response in total Hb (increase of ≥1.0 g/dL)	Baseline to Week 24, and Week 52
Change in hemolysis biomarkers	a. Change in hemolysis biomarkers (% and absolute reticulocytes, unconjugated (indirect) bilirubin, and lactate dehydrogenase (LDH)	Baseline to Week 24, and Week 52
Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®)	a. Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®).	Baseline to Week 24, and Week 52
Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS)	a. The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]).	Baseline to Week 24, and Week 52
Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES)	a. Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES).	Baseline to Week 24, and Week 52
Changes in biomarker of adhesion	a. Changes in biomarkers of adhesion such as soluble E-selectin, P-selectin, ICAM-1, and VCAM-1	Baseline to Week 24 and Week 52
Changes in inflammation biomarkers	a. Changes in biomarkers of inflammation such as high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO)	Baseline to Week 24 and Week 52
Changes in cardiac stress biomarkers	a. Changes in biomarkers of cardiac stress such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)	Baseline to Week 24 and Week 52
Effect on Red Blood Cell (RBC) indices	a. Changes in RBC indices, such as mean corpuscular volume (MCV)	Baseline to Week 24 and Week 52

Collaborators and Investigators

• Sponsor: Cardurion Pharmaceuticals, Inc.
• Collaborators: Imara, Inc.
• Investigators: Study Director: Kenneth Attie, MD, Imara, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Sickle Cell Disease
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: IMR-SCD-301; 2019-004471-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No