June 26, 2020
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July 16, 2020
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May 13, 2022
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August 13, 2020
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March 2, 2022 (Final data collection date for primary outcome measure)
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- 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)
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- 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".
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Not Provided
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Not Provided
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A Study of IMR-687 in Subjects With Sickle Cell Disease
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A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
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A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease
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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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Interventional
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Phase 2
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Masking Description: Double-Blind Primary Purpose: Treatment
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Sickle Cell Disease
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- 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
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Not Provided
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Terminated
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115
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99
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May 4, 2022
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March 2, 2022 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)
- Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.
- 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).
- 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.
- Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
- Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
Exclusion Criteria:
- Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
- 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
- Subjects with HbF >25% at screening.
- Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase >3x upper limit of normal.
- Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a BMI >35 kg/m2.
- 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).
- Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).
- Prior exposure to IMR-687.
- 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).
- A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
- 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.
- Prior gene therapy.
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Sexes Eligible for Study: |
All |
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18 Years to 65 Years (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Ghana, Greece, Italy, Kenya, Lebanon, Morocco, Netherlands, Oman, Senegal, Tunisia, Uganda, United Kingdom, United States
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NCT04474314
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IMR-SCD-301 2019-004471-39 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Not Provided
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Imara, Inc.
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Same as current
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Imara, Inc.
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Same as current
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Not Provided
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Study Director: |
Kenneth Attie, MD |
Imara, Inc. |
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Imara, Inc.
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March 2022
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