A Study of IMR-687 in Healthy Adult Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1a Study of IMR-687 in Healthy Adult Volunteers

Conditions
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Sickle Cell Disease, Sickle-Cell; Hb-SC, Sickle Beta 0 Thalassemia

Intervention / Treatment
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* Drug: IMR-687
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Cohort 2<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Cohort 3<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Cohort 4<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Cohort 5<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Cohort 6<br>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<br>* 1 of 6 possible single doses administered orally following overnight fast<br>Drug: Placebo Oral Capsule<br>* Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.<br>* Other names: Microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of IMR-687 | Maximum Observed Plasma Concentration (Cmax) of IMR-687 | 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 | 
| Pharmacokinetics (PK) of IMR-687 | Area under the curve (AUC) ( 0 to 24 h) of IMR-687 | 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 | 
| Pharmacokinetics (PK) of IMR-687 | AUC from time 0 to the last measurable time point (AUClast) of IMR-687 | 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 | 
| Pharmacokinetics (PK) of IMR-687 | AUC extrapolated to infinity (AUC0 ∞) of IMR-687 | 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 | 
| Pharmacokinetics (PK) of IMR-687 | Time to maximum concentration (tmax) of IMR-687 | 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 | 
| Pharmacokinetics (PK) of IMR-687 | Apparent terminal half-life (t½) of IMR-687 | 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 | 
| The change from baseline in QTcF interval. |  | 2 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Sickle Beta 0 Thalassemia