Back to resultsA Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)
Primary Purpose
Sickle Cell Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IMR-687
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility 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
Sites / Locations
- UCSF Benioff Children's Hospital Oakland
- University of Connecticut Health Center
- Foundation for Sickle Cell Disease Research
- University of Illinois
- Loretto Hospital
- Medical University of South Carolina
- Baylor Scott & White Health
- Sandwell & West Birmingham Hospital
- Bristol Haematology and Oncology Centre
- Royal London Hospital
- University College London Hospital
- Guy's Hospital
- Oxford Cancer & Haematology Centre, The Churchill Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
IMR-687 50 mg/100 mg
IMR-687 100 mg/200 mg
Placebo
Arm Description
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).
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).
Matching placebo was administered for 16 (Week 17) or 24 weeks (Week 25).
Outcomes
Primary Outcome Measures
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs)
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
Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687
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.
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
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.
PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687
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.
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687
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.
PK Of Participants Who Concomitantly Received HU: Cmax Of HU
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.
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03401112
Brief Title
A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 26, 2018 (Actual)
Primary Completion Date
August 28, 2020 (Actual)
Study Completion Date
August 28, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imara, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study of IMR-687 in adult participants with sickle cell anemia (SCA) (homozygous HbSS or sickle-β0 thalassemia).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double-blind
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IMR-687 50 mg/100 mg
Arm Type
Experimental
Arm Description
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).
Arm Title
IMR-687 100 mg/200 mg
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo was administered for 16 (Week 17) or 24 weeks (Week 25).
Intervention Type
Drug
Intervention Name(s)
IMR-687
Intervention Description
Oral administration of IMR-687 once daily with or without HU.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration of placebo once daily with or without HU.
Primary Outcome Measure Information:
Title
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs)
Description
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.
Time Frame
Day 1 (after dosing) through up to Week 24
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687
Description
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.
Time Frame
Day 1 and Week 25
Title
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
Description
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.
Time Frame
Day 1 and Week 25
Title
PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687
Description
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.
Time Frame
Day 1 and Week 17
Title
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687
Description
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.
Time Frame
Day 1 and Week 17
Title
PK Of Participants Who Concomitantly Received HU: Cmax Of HU
Description
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.
Time Frame
Baseline (1 and 2) and Week 17
Title
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU
Description
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.
Time Frame
Baseline (1 and 2) and Week 17
Other Pre-specified Outcome Measures:
Title
Change From Baseline In F-Cells
Description
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.
Time Frame
Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Regulatory Operations
Organizational Affiliation
Cardurion Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
Foundation for Sickle Cell Disease Research
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Loretto Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60644
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Baylor Scott & White Health
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Sandwell & West Birmingham Hospital
City
Birmingham
ZIP/Postal Code
B18 7QH
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Facility Name
Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
University College London Hospital
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Oxford Cancer & Haematology Centre, The Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)
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