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

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: IMR-687; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Sandwell & West Birmingham Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, E1 1BB
    • Royal London Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospital
  • Oxford, United Kingdom, OX3 7LE
    • Oxford Cancer & Haematology Centre, The Churchill Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Florida
    • Hollywood, Florida, United States, 33021
      • Foundation for Sickle Cell Disease Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60644
      • Loretto Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 (after dosing) through up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 and Week 25
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.	Day 1 and Week 25
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.	Day 1 and Week 17
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.	Day 1 and Week 17
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.	Baseline (1 and 2) and Week 17
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.	Baseline (1 and 2) and Week 17

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In F-Cells	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.	Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU)

Collaborators and Investigators

• Sponsor: Imara, Inc.
• Investigators: Principal Investigator: Timothy Mant, MB FFPM FRCP, Guy's and St Thomas Hospital CRF

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2018
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): August 28, 2020

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: January 9, 2018
• First Posted (Actual): January 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Thalassemia
• Other Study ID Numbers: IMR-SCD-102; 2017-000653-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No