Study to Assess CMR316 in Healthy Volunteers and Patients With Idiopathic Pulmonary Fibrosis

NCT06589219 | Recruiting Phase 1

• 1 other identifier: CBR-CMR316-3001
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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).

Conditions

Pulmonary Fibroses, Idiopathic

Keywords

Pulmonary; IPF; Inhaled therapy

Outcome Measures

Primary Outcomes (5)

• Number of participants with adverse events

  Adverse events will be analyzed for severity and potential relationship to CMR316 to determine safety and tolerability of CMR316

  Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26; Part 3: Day 1 through Day 26

• Number of participants with clinically significant abnormal physical exam and vital signs

  Vital signs will include evaluation of systolic and/or diastolic blood pressure (mmHg), heart rate (beats/min), temperature (Celsius), and respiratory rate (breaths/minute).

  Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26; Part 3: Day 1 through Day 26

• Number of patients with reduced pulmonary function

  Pulse oximeter will analyze oxygen saturation, spirometry will include evaluation of FEV1, FVC, and FEV1/FVC, and DLCO

  Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26; Part 3: Day 1 through Day 26

• Number of participants with abnormal electrocardiogram readings

  Electrocardiogram will include an evaluation of QTcF interval, ventricular rate, PR interval, QRS duration and QRS axis

  Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26; Part 3: Day 1 through Day 26

• Number of participants with clinically significant abnormal laboratory test results

  Results outside of laboratory defined normal ranges will be analyzed for clinical significance and used to determine safety and tolerability of CMR316

  Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26; Part 3: Day 1 through Day 26

Secondary Outcomes (3)

• Assess pharmacokinetics, AUC, as available

  Part 1: Day 1 through Day 15; Part 2: Day 1 through Day 36; Part 3: Day 1 through Day 36

• Assess pharmacokinetics, Cmax, as available

  Part 1: Day 1 through Day 15; Part 2: Day 1 through Day 36; Part 3: Day 1 through Day 36

• Assess pharmacodynamics, characterize enzymatic activity

  Part 1: Day 1 though Day 8; Part 2: Day 1 through Day 29; Part 3: Day 1 through Day 29

Study Arms (5)

Part 1 SAD CMR316

ACTIVE COMPARATOR

Single ascending dose, nebulized administration of CMR316

Drug: CMR316

Part 1 SAD Placebo

PLACEBO COMPARATOR

Single ascending dose, nebulized administration of matching placebo

Drug: Placebo

Part 2 MAD CMR316

ACTIVE COMPARATOR

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

Drug: CMR316

Part 2 MAD Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part 3 IPF Patients

EXPERIMENTAL

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

Drug: CMR316

Interventions

CMR316 DRUG

CMR316 administered via nebulization at single or multiple dose(s) assigned by cohort

Part 1 SAD CMR316; Part 2 MAD CMR316; Part 3 IPF Patients

Placebo DRUG

Placebo administered via nebulization at single or multiple dose(s) to match CMR316 administration

Part 1 SAD Placebo; Part 2 MAD Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• Men or non-pregnant, non-lactating women of non-childbearing potential.
• Age ≥ 40 years.
• Mild to moderate IPF as defined by predicted FVC ≥ 55% of normal and predicted DLCO \> 40% of normal at Screening.
• Subjects receiving oral pirfenidone or nintedanib for treatment of IPF may participate if they have been on treatment with a stable, well-tolerated dose (as determined by the investigator), for at least 8 weeks prior to consent with no changes to therapy dose and schedule anticipated during the course of study participation.
• Must be able to understand a written informed consent, which must be obtained prior to any study procedures.
• Must be willing and able to comply with all study requirements

You may not qualify if:

• 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.
• Subjects who have received any investigational medicinal product (IMP) in a clinical research study within 5 half-lives or within 30 days prior to first dose (whichever is longer).
• Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2.
• Subjects who have taken, any over-the-counter drug or herbal remedies in the 15 days prior to first IMP administration. Subjects taking prescribed medication in the 90 days prior to first IMP administration. Subjects taking up to 4 g per day of acetaminophen may participate if discontinued at least 15 days prior to first IMP administration. Subjects taking DPP4 inhibitors are prohibited. Subjects taking strong CYP3A inhibitors are prohibited.
• History of any substance use disorder or alcohol use disorder in the past 2 years, as based on the diagnostic criteria in the Diagnostic and Statistical Manual Fifth Edition (DSM-5).
• Regular alcohol consumption in men \>21 units per week and women \>14 units per week (1 unit = 12 oz 1 bottle/can of beer, 1 oz 40% spirit, or 5 oz glass of wine).
• A confirmed positive alcohol breath test at screening or first admission.

Sponsors & Collaborators

• Calibr, a division of Scripps Research: lead

Study Sites (1)

Fraunhofer Institute for Toxicology and Experimental Medicine ITEM

Hanover, 30625, Germany

RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chan Beals, MD, PhD

  Calibr-Skaggs Institute for Innovative Medicines

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathalie Luis

CONTACT

nluis@scripps.edu

Alex Brooks

CONTACT

858-242-1000; abrooks@scripps.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The majority of this study will be conducted double-blind; treatment assignment will not be known to the subjects, the Sponsor (with exception of an unblinded bioanalytical specialist who will review PK and PD and blind data for presentation to blinded team) and staff involved in the clinical evaluation of the subjects and the analysis of data. The randomization schedule and disclosure envelopes will be generated by an unblinded statistical team. The unblinded statistical team will not be involved in decisions relating to populations for analysis prior to unblinding. Prior to database lock and unblinding, all original randomization materials will be held by the unblinded statistical team. There may be instances where interim data has the potential to reveal treatment. In these cases, every effort will be made by the unblinded bioanalytical specialist to maintain blinding by appropriate presentation of data to the study team.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1 Cohorts 1-4: double-blind, assess single ascending doses (SAD) of nebulized CMR316. Cohort 5: open label, single dose (at a dose previously determined to be safe) \& incl. lung sample collection via bronchoscopy for PK \& PD. Part 2: double blind, assess multiple ascending dose (MAD) cohorts of CMR316 administered once weekly for 4 weeks. If further PK/PD data from lung samples is required to determine appropriate RP2D then a sub-group of open-label participants who will undergo bronchoscopies may be enrolled to any or all MAD cohorts. Parts 1 \&2 are not required to be conducted entirely sequentially if justified by PK \& safety obtained. The first MAD cohort will not start until data are available from SAD Cohort 3 \& dosing for each MAD cohort will not exceed a dose level previously deemed safe in a SAD cohort. Part 3: IPF patients, will not start until data are available and reviewed from Parts 1 \& 2 and will not exceed a dose level previously deemed safe in a SAD/MAD cohort.

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: September 19, 2024
• Study Start: August 19, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)