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

Sickle Cell Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03401112
• Other study ID #: IMR-SCD-102
• Secondary ID: 2017-000653-39
• Status: Completed
• Phase: Phase 2
• Start date: January 26, 2018
• Est. completion date: August 28, 2020

Study information

• Verified date: March 2022
• Source: Imara, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 28, 2020
• Est. primary completion date: August 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• IMR-687
Oral administration of IMR-687 once daily with or without HU.
• Placebo
Oral administration of placebo once daily with or without HU.

Locations

Country	Name	City	State
United Kingdom	Sandwell & West Birmingham Hospital	Birmingham
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Guy's Hospital	London
United Kingdom	Royal London Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	Oxford Cancer & Haematology Centre, The Churchill Hospital	Oxford
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Loretto Hospital	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Foundation for Sickle Cell Disease Research	Hollywood	Florida
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Baylor Scott & White Health	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Imara, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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