A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)
- Registration Number
- NCT03401112
- Lead Sponsor
- Cardurion Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMR-687 50 mg/100 mg IMR-687 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). IMR-687 100 mg/200 mg IMR-687 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). Placebo Placebo Matching placebo was administered for 16 (Week 17) or 24 weeks (Week 25).
- Primary Outcome Measures
Name Time Method Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) 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
Name Time Method PK Of Participants Who Concomitantly Received HU: Cmax Of HU 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.
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU 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.
Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687 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.
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 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.
PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687 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.
PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687 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.
Trial Locations
- Locations (13)
Loretto Hospital
🇺🇸Chicago, Illinois, United States
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
University of Illinois
🇺🇸Chicago, Illinois, United States
Foundation for Sickle Cell Disease Research
🇺🇸Hollywood, Florida, United States
Sandwell & West Birmingham Hospital
🇬🇧Birmingham, United Kingdom
Baylor Scott & White Health
🇺🇸Temple, Texas, United States
Royal London Hospital
🇬🇧London, United Kingdom
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
University College London Hospital
🇬🇧London, United Kingdom
Oxford Cancer & Haematology Centre, The Churchill Hospital
🇬🇧Oxford, United Kingdom
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Guy's Hospital
🇬🇧London, United Kingdom