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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04474314
Recruitment Status : Active, not recruiting
First Posted : July 16, 2020
Last Update Posted : August 27, 2021
Sponsor:
Information provided by (Responsible Party):
Imara, Inc.

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

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: IMR-687 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
Actual Study Start Date : August 13, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Higher dose IMR-687
Oral administration of once daily IMR-687
Drug: IMR-687
Oral administration of once daily IMR-687

Experimental: Lower 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




Primary Outcome Measures :
  1. Subject response in HbF [ Time Frame: Baseline to Week 24 ]
    a. Subject response in HbF (increase of ≥3%)

  2. Proportion of patients with adverse events and serious adverse events [ Time Frame: Baseline to Week 56 ]
    1. Incidence of Adverse Events
    2. Incidence of Serious Adverse Events


Secondary Outcome Measures :
  1. Effect on the incidence of vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Annualized rate of VOCs

  2. Time to first vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Time to first VOC

  3. Annualized rate of hospitalizations for vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Annualized rate of hospitalizations for VOCs

  4. Time to second vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Time to second VOC

  5. Subject response in HbF [ Time Frame: Baseline to Week 52 ]
    a. Subject response in HbF (increase of ≥3%)

  6. Change in HbF and F Cells [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Change in HbF (%) and F-cells (%)

  7. Subject response in total Hb [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Subject response in total Hb (increase of ≥1.0 g/dL)

  8. Change in hemolysis biomarkers [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Change in hemolysis biomarkers (% and absolute reticulocytes, unconjugated (indirect) bilirubin, and lactate dehydrogenase (LDH)

  9. Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®).

  10. Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]).

  11. Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES).

  12. Changes in biomarker of adhesion [ Time Frame: Baseline to Week 24 and Week 52 ]
    a. Changes in biomarkers of adhesion such as soluble E-selectin, P-selectin, ICAM-1, and VCAM-1

  13. Changes in inflammation biomarkers [ Time Frame: Baseline to Week 24 and Week 52 ]
    a. Changes in biomarkers of inflammation such as high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO)

  14. Changes in cardiac stress biomarkers [ Time Frame: Baseline to Week 24 and Week 52 ]
    a. Changes in biomarkers of cardiac stress such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)

  15. Effect on Red Blood Cell (RBC) indices [ Time Frame: Baseline to Week 24 and Week 52 ]
    a. Changes in RBC indices, such as mean corpuscular volume (MCV)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04474314


Locations
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Sponsors and Collaborators
Imara, Inc.
Investigators
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Study Director: Kenneth Attie, MD Imara, Inc.
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Responsible Party: Imara, Inc.
ClinicalTrials.gov Identifier: NCT04474314    
Other Study ID Numbers: IMR-SCD-301
2019-004471-39 ( EudraCT Number )
First Posted: July 16, 2020    Key Record Dates
Last Update Posted: August 27, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imara, Inc.:
Sickle Cell Disease
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn