A Study of IMR-687 in Healthy Adult Volunteers

• ClinicalTrials.gov Identifier: NCT02998450
• Recruitment Status: Completed
• First Posted: December 20, 2016
• Last Update Posted: March 8, 2023
• Sponsor: Imara, Inc.
• Collaborator: Quintiles, Inc.
• Information provided by (Responsible Party): Imara, Inc.

Study Description

Brief Summary:

The purpose of this Phase 1a, first in human, randomized, double-blind, placebo-controlled study is to evaluate the safety, tolerability, PK and PD profile of the orally administered IMR-687 in healthy adult subjects.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Disease; Sickle-Cell; Hb-SC; Sickle Beta 0 Thalassemia	Drug: IMR-687; Drug: Placebo Oral Capsule	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1a Study of IMR-687 in Healthy Adult Volunteers
• Actual Study Start Date: October 18, 2016
• Actual Primary Completion Date: July 8, 2017
• Actual Study Completion Date: July 8, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; 4 Subjects will receive a single low dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose
Experimental: Cohort 2; 4 Subjects will receive a single low-mid dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose
Experimental: Cohort 3; 4 Subjects will receive a single mid-low dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose
Experimental: Cohort 4; 4 Subjects will receive a single mid dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose
Experimental: Cohort 5; 4 Subjects will receive a single mid-high dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose
Experimental: Cohort 6; 4 Subjects will receive a single high dose of IMR-687, administered orally following an overnight fast. 2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.	Drug: IMR-687; 1 of 6 possible single doses administered orally following overnight fast; Drug: Placebo Oral Capsule; Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.; Other Name: Microcrystalline cellulose

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment emergent adverse events and serious adverse events [ Time Frame: 5 Days ]
2. Number of participants with clinically significant changes from baseline in vital signs [ Time Frame: Baseline to Day 5 ]
   Vital signs include blood pressure, heart rate, pulse rate, and oral temperature
3. Number of participants with clinically significant changes from baseline in physical examination [ Time Frame: Baseline to Day 5 ]
4. Number of participants with clinically significant changes from baseline in hematology, chemistry, coagulation and urinalysis laboratory values [ Time Frame: Baseline to Day 5 ]
5. Number of participants with clinically significant changes from baseline in 12-lead ECG parameters [ Time Frame: Baseline to Day 2 ]
6. Use of concomitant medications and therapies, medication type and frequency [ Time Frame: 5 Days ]

Secondary Outcome Measures :

1. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   Maximum Observed Plasma Concentration (Cmax) of IMR-687
2. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   Area under the curve (AUC) ( 0 to 24 h) of IMR-687
3. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   AUC from time 0 to the last measurable time point (AUClast) of IMR-687
4. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   AUC extrapolated to infinity (AUC0 ∞) of IMR-687
5. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   Time to maximum concentration (tmax) of IMR-687
6. Pharmacokinetics (PK) of IMR-687 [ Time Frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose ]
   Apparent terminal half-life (t½) of IMR-687
7. The change from baseline in QTcF interval. [ Time Frame: 2 Days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Be healthy as judged by the Investigator on the basis of pre-study tests performed at Screening, with healthy body mass index (BMI), healthy body weight, and laboratory results within normal laboratory reference range or determined not to be clinically significant by the Investigator; and be free from drugs of abuse.

Exclusion Criteria:

• Females who are pregnant, trying to become pregnant, or breastfeeding; and males with female partners who are trying to conceive.
• Asthmatics or other individuals who use or may use albuterol rescue inhalers or nebulizers.
• A significant history of cardiovascular disease.
• On ECG, a QTcF >450 ms or the presence of clinically significant abnormalities as determined by the Investigator.
• Elevated blood pressure.
• Use within 30 days prior to Day 1 of any inhibitors or substrates of targets of IMR-687.

Contacts and Locations

Locations

United States, Kansas

Quintiles

Overland Park, Kansas, United States, 66211

Sponsors and Collaborators

Imara, Inc.

Quintiles, Inc.

Investigators

• Study Director: Regulatory Operations; Cardurion Pharmaceuticals

More Information

• Responsible Party: Imara, Inc.
• ClinicalTrials.gov Identifier: NCT02998450
• Other Study ID Numbers: IMR-SCD-101
• First Posted: December 20, 2016
• Last Update Posted: March 8, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Imara, Inc.:

Sickle Cell Disease; Sickle Beta 0 Thalassemia

Additional relevant MeSH terms:

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