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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 : Terminated (A recently conducted Interim analysis of IMR-SCD-301 demonstrated that while IMR-687 was generally well-tolerated, it failed to meet its primary efficacy endpoint. So, the sponsor has decided to discontinue this study.)
First Posted : July 16, 2020
Last Update Posted : May 13, 2022
Sponsor:
Information provided by (Responsible Party):
Imara, Inc.

Tracking Information
First Submitted Date  ICMJE June 26, 2020
First Posted Date  ICMJE July 16, 2020
Last Update Posted Date May 13, 2022
Actual Study Start Date  ICMJE August 13, 2020
Actual Primary Completion Date March 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2022)
  • Effect on the incidence of vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 52 ]
    a. Annualized rate of VOCs
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
  • Subject response as defined by an increase of ≥3% in HbF [ Time Frame: Baseline to Week 24 ]
    a. Subject response in HbF (increase of ≥3%)
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2022)
  • Time to first vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 52 ]
    a. Time to first VOC
  • Proportion of HbF response [ Time Frame: Baseline to Week 24 ]
    a. Proportion of Subject with response to HbF (absolute increase of ≥3%)
  • Proportion of VOC-free subject [ Time Frame: Baseline to Week 52 ]
  • 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
  • Time to second vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Time to second VOC
  • Proportion of HbF response [ Time Frame: Baseline to Week 52 ]
    a. Proportion of Subject with response to HbF (absolute increase of ≥3%)
  • Change in HbF and F Cells [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Change in HbF (%) and F-cells (%)
  • Proportion of Subject response in total Hb [ Time Frame: Baseline to Week 24, and Week 52 ]
    a. Proportion of Subject response in total Hb (increase of ≥1.0 g/dL)
  • 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)
  • 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®).
  • 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]).
  • 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).
  • 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
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
  • Change in HbF [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a. Change in HbF
  • Subject response as defined by an increase of ≥3% in HbF [ Time Frame: Baseline to Week 36, and Week 52 ]
    a) Subject response in HbF (increase of ≥3%)
  • Change in % F cells [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) Change in % F cells
  • Change in hemolysis markers (% and absolute reticulocytes) [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) Change in hemolysis markers
  • Effect on indices of white blood cell (WBC) adhesion markers [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) Change in WBC adhesion markers
  • Effect on on the incidence of vaso-occlusive crises (VOCs) [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) Change in the number of VOCs
  • Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®) [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®). The questions are ranked on a 5-point Likert Scale and there is one 11-point rating scale for pain intensity. High scores represent more of the domain being measured.
  • Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS) [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    a) The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr] ). The questions are ranked on a 5-point Likert Scale and there is one 11-point rating scale for pain intensity. High scores represent more of the domain being measured.
  • Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES) [ Time Frame: Baseline to Week 24, Week 36, and Week 52 ]
    2) Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES). The SCES is a 9-item QoL. Responses range from "not at all sure" to "very sure".
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of IMR-687 in Subjects With Sickle Cell Disease
Official Title  ICMJE A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-Blind
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: IMR-687
    Oral administration of once daily IMR-687
  • Drug: Placebo
    Oral administration of once daily Placebo
Study Arms  ICMJE
  • Experimental: Higher dose IMR-687
    Oral administration of once daily IMR-687
    Intervention: Drug: IMR-687
  • Experimental: Lower Dose IMR-687
    Oral administration of once daily IMR-687
    Intervention: Drug: IMR-687
  • Placebo Comparator: Placebo
    Oral administration of once daily Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 9, 2022)
115
Original Estimated Enrollment  ICMJE
 (submitted: July 15, 2020)
99
Actual Study Completion Date  ICMJE May 4, 2022
Actual Primary Completion Date March 2, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ghana,   Greece,   Italy,   Kenya,   Lebanon,   Morocco,   Netherlands,   Oman,   Senegal,   Tunisia,   Uganda,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04474314
Other Study ID Numbers  ICMJE IMR-SCD-301
2019-004471-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Imara, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Imara, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kenneth Attie, MD Imara, Inc.
PRS Account Imara, Inc.
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP