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

• 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: Imara, Inc.
• Information provided by (Responsible Party): Imara, Inc.

Study Description

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.

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• 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

More Information

• 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
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anemia, Sickle Cell; Thalassemia; Anemia; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Genetic Diseases, Inborn