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A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)

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: NCT03401112
Recruitment Status : Completed
First Posted : January 17, 2018
Results First Posted : April 14, 2022
Last Update Posted : April 14, 2022
Sponsor:
Information provided by (Responsible Party):
Imara, Inc.

Brief Summary:
Study of IMR-687 in adult participants with sickle cell anemia (SCA) (homozygous HbSS or sickle-β0 thalassemia).

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

Detailed Description:

This is a proof-of-concept study in adult SCA participants, ages 18 to 55 years old, to examine the safety, tolerability, and pharmacokinetic (PK), as well as the potential pharmacodynamic (PD) effects and clinical efficacy, of IMR-687 across a range of doses.

IMR-687 was administered in 2 populations of participants with SCA: those who were not receiving hydroxyurea (HU) and those who were receiving a stable dose of HU according to standard of care.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients With Sickle Cell Anaemia (Homozygous HbSS or Sickle-β0 Thalassemia)
Actual Study Start Date : January 26, 2018
Actual Primary Completion Date : August 28, 2020
Actual Study Completion Date : August 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Thalassemia

Arm Intervention/treatment
Experimental: IMR-687 50 mg/100 mg
A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants. Duration of administration was 16 (Week 17) or 24 weeks (Week 25).
Drug: IMR-687
Oral administration of IMR-687 once daily with or without HU.

Experimental: IMR-687 100 mg/200 mg
A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants. Duration of administration was 24 weeks (Week 25).
Drug: IMR-687
Oral administration of IMR-687 once daily with or without HU.

Placebo Comparator: Placebo
Matching placebo was administered for 16 (Week 17) or 24 weeks (Week 25).
Drug: Placebo
Oral administration of placebo once daily with or without HU.




Primary Outcome Measures :
  1. Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) [ Time Frame: Day 1 (after dosing) through up to Week 24 ]
    An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An SAE was defined as any AE that resulted in 1 or more of the following outcomes: death, required or prolonged hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, or other medically important event. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687 [ Time Frame: Day 1 and Week 25 ]
    For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.

  2. PK Of Participants Who Did Not Concomitantly Receive HU: Area Under The Concentration-time Curve (AUC) From Time 0 To 24 Hours Postdose (AUC0-24h) Of IMR-687 [ Time Frame: Day 1 and Week 25 ]
    For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.

  3. PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687 [ Time Frame: Day 1 and Week 17 ]
    For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 PK were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.

  4. PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687 [ Time Frame: Day 1 and Week 17 ]
    For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.

  5. PK Of Participants Who Concomitantly Received HU: Cmax Of HU [ Time Frame: Baseline (1 and 2) and Week 17 ]
    For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (end of treatment [EOT]: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.

  6. PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU [ Time Frame: Baseline (1 and 2) and Week 17 ]
    For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (EOT: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.


Other Outcome Measures:
  1. Change From Baseline In F-Cells [ Time Frame: Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU) ]
    Absolute least squares (LS) mean change from baseline at EOT is presented. Change from baseline in pharmacodynamic (PD) biomarkers was analyzed using mixed models for repeated measures with covariate of treatment, visit, treatment-by-visit interaction, and baseline value.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female participants with confirmed SCA
  • Age 18 to 55 years, inclusive
  • For participants on HU, must have been on a stable dose for at least 60 days prior to screening

Key Exclusion Criteria:

  • Total hemoglobin >12.5 or <6 grams/deciliter
  • Red blood cell transfusion within 60 days of baseline
  • >7 hospitalizations for vaso-occlusive crises (VOCs) within the last year
  • Estimated glomerular filtration rate <50 milliliter/minute
  • Aspartate aminotransferase/alanine aminotransferase >3x the upper limit of normal

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): NCT03401112


Locations
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United States, California
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, Florida
Foundation for Sickle Cell Disease Research
Hollywood, Florida, United States, 33021
United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60612
Loretto Hospital
Chicago, Illinois, United States, 60644
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor Scott & White Health
Temple, Texas, United States, 76508
United Kingdom
Sandwell & West Birmingham Hospital
Birmingham, United Kingdom, B18 7QH
Bristol Haematology and Oncology Centre
Bristol, United Kingdom, BS2 8ED
Royal London Hospital
London, United Kingdom, E1 1BB
University College London Hospital
London, United Kingdom, NW1 2PG
Guy's Hospital
London, United Kingdom, SE1 9RT
Oxford Cancer & Haematology Centre, The Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Sponsors and Collaborators
Imara, Inc.
Investigators
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Principal Investigator: Timothy Mant, MB FFPM FRCP Guy's and St Thomas Hospital CRF
  Study Documents (Full-Text)

Documents provided by Imara, Inc.:
Study Protocol  [PDF] June 28, 2019
Statistical Analysis Plan  [PDF] December 22, 2020

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Responsible Party: Imara, Inc.
ClinicalTrials.gov Identifier: NCT03401112    
Other Study ID Numbers: IMR-SCD-102
2017-000653-39 ( EudraCT Number )
First Posted: January 17, 2018    Key Record Dates
Results First Posted: April 14, 2022
Last Update Posted: April 14, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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