A Phase 1/1B Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Nebulized CMR316 in Healthy Volunteers and Patients With Idiopathic Pulmonary Fibrosis

Calibr, a division of Scripps Research1 site in 1 country106 target enrollmentAugust 19, 2024

ConditionsPulmonary Fibroses, Idiopathic

InterventionsCMR316 Placebo

DrugsCMR316 Placebo

Overview

Phase: Phase 1
Intervention: CMR316
Conditions: Pulmonary Fibroses, Idiopathic
Sponsor: Calibr, a division of Scripps Research
Enrollment: 106
Locations: 1
Primary Endpoint: Number of participants with adverse events
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics single and multiple inhaled doses of CMR316 in healthy volunteers and patients with Idiopathic Pulmonary Fibrosis (IPF).

Detailed Description

This is a 3-part, single-center study; Part 1 will evaluate single ascending doses (SAD) and Part 2 will evaluate multiple ascending doses (MAD; once weekly dosing for 4 weeks) of nebulized CMR316 or placebo in healthy male and female subjects. Part 3 will assess multiple doses (once weekly dosing for 4 weeks) of nebulized CMR316 (open-label) in subjects with IPF.

Registry

clinicaltrials.gov

Start Date

August 19, 2024

End Date

March 2026

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Calibr, a division of Scripps Research

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Part 1 \& 2
•Healthy men or non-pregnant, non-lactating healthy women of non-childbearing potential, 18-60 years of age.
•Must agree to use a highly effective method of contraception.
•Body Mass Index (BMI) 18-33 kg/m2 as measured at screening.
•Weight ≤100 kg at screening.
•Normal lung function, defined as: FVC and FEV1 \> 80% predicted (based on age, height, race, sex, SaO2 \> 95% on room air.
•Heart rate between 50 and 90 beats per minute (BPM).
•Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination) and screening safety procedures.
•Inclusion Criteria: Part 3
•Diagnosis of IPF by American Thoracic Society/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Latin America Thoracic Society) 2011 criteria within five years prior to consent.

Exclusion Criteria

•Part 1 \& 2
•Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
•Presence or history of clinically significant hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) or allergy as judged by the investigator. Subjects with a history of seasonal rhinitis (hay fever) or childhood asthma may participate if these conditions are not active or expected to be active during the subject's participation.
•History of clinically significant cardiovascular, skin, renal, hepatic, respiratory or gastrointestinal disease (except cholecystectomy), neurological or psychiatric disorder, illness/infection/hospitalization, or surgical procedure within 30 days prior to first dose of study drug. Subjects with a history of pancreatitis, heart failure, acute renal failure, bullous pemphigoid, or severe and disabling arthritis, conditions associated with postmarketing safety reports of oral gliptins, are excluded.
•Have poor venous access that limits phlebotomy.
•Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin above upper limit of normal (elevated bilirubin in subject's with Gilbert Syndrome is allowed) or other clinically significant abnormal clinical chemistry, hematology, or urinalysis as judged by the investigator.
•Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) antibody results.
•Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<90 mL/min using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Appendix 1: CKD-EPI Equation).
•Subjects with a corrected QT interval by Fredericia (QTcF) of \>450 msec at screening or first admission.
•Positive highly sensitive serum pregnancy test at screening or highly sensitive urine pregnancy test at first admission. Those who are pregnant or lactating will be excluded.

Arms & Interventions

Part 1 SAD CMR316

Single ascending dose, nebulized administration of CMR316

Intervention: CMR316

Part 1 SAD Placebo

Single ascending dose, nebulized administration of matching placebo

Intervention: Placebo

Part 2 MAD CMR316

Multiple ascending dose, nebulized administration of CMR316 once weekly for 4 weeks

Intervention: CMR316

Part 2 MAD Placebo

Multiple ascending dose, nebulized administration of matching placebo once weekly for 4 weeks

Intervention: Placebo

Part 3 IPF Patients

Open-label, nebulized administration of CMR316 once weekly for 4 weeks for patients with IPF

Intervention: CMR316