Study to Evaluate the Safety of CB-280 in Patients With Cystic Fibrosis

NCT ID: NCT04279769

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-03
• Study Completion Date: 2021-11-23

Brief Summary

This is a phase 1b multiple ascending dose escalation study to evaluate the safety and tolerability of arginase inhibitor CB-280 in subjects with cystic fibrosis.

Detailed Description

Study CX-280-202 is a Phase 1b, randomized, double-blind, placebo-controlled, multiple ascending dose escalation study of CB-280 in adult subjects with cystic fibrosis and chronic infection with Pseudomonas aeruginosa. The study will evaluate the safety, pharmacokinetics, pharmacodynamics, and biological activity of CB-280 in approximately 32 adult patients with cystic fibrosis. There are four planned sequential dose escalation cohorts of 8 subjects each, randomized 6:2 to receive CB-280 or matched placebo at doses of 50 mg, 100 mg, 200 mg, or 400 mg administered twice daily for 14 days. Intermediate dose levels may be evaluated based on emerging safety data at the planned dose levels.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1

CB-280 twice daily at 50 mg for 14 days

Group Type: EXPERIMENTAL

CB-280

Intervention Type: DRUG

CB-280, oral capsule administered twice daily at the assigned dose level for 14 days

Cohort 2

CB-280 twice daily at 100 mg for 14 days

Group Type: EXPERIMENTAL

CB-280

Intervention Type: DRUG

CB-280, oral capsule administered twice daily at the assigned dose level for 14 days

Cohort 3

CB-280 twice daily at 200 mg for 14 days

Group Type: EXPERIMENTAL

CB-280

Intervention Type: DRUG

CB-280, oral capsule administered twice daily at the assigned dose level for 14 days

Cohort 4

CB-280 twice daily at 400 mg for 14 days

Group Type: EXPERIMENTAL

CB-280

Intervention Type: DRUG

CB-280, oral capsule administered twice daily at the assigned dose level for 14 days

Placebo

Placebo twice daily for 14 days

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Placebo oral capsule administrated twice daily at the assigned dose level for 14 days

Interventions

CB-280

CB-280, oral capsule administered twice daily at the assigned dose level for 14 days

Intervention Type: DRUG

Placebos

Placebo oral capsule administrated twice daily at the assigned dose level for 14 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Written Informed Consent in accordance with federal, local, and institutional guidelines

2. Confirmed diagnosis of cystic fibrosis

3. Male or female subjects ≥ 18 years on the date of informed consent

4. Percent predicted FEV1 of 40-90% at screening per Global Lung Function Initiative (GLI) equation

5. Clinically stable with no significant changes in health status within 28 days prior to Day 1

6. Chronic lung infection with P. aeruginosa defined as at least one positive culture in the last two years and more than 50% of cultures positive since then

7. Stable cystic fibrosis medication regimen for at least 28 days inclusive of CFTR modulators prior to Day 1

8. Hemoglobin > 10 g/dL at screening

9. Glomerular filtration rate > 50 mL/min/1.73 m2 at screening

10. Normal liver function at screening

Exclusion Criteria

1. History of any comorbidity that, in the opinion of the Investigator, might pose an additional risk in administering study drug to the subject or confound the results of the study

2. Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus)

3. Unable to receive study medication per os (PO)

4. Females who are pregnant, have a positive pregnancy test at screening, or are nursing (lactating)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emil T Kuriakose, MD

Role: STUDY_DIRECTOR

Calithera Bioscience

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Long Beach Memorial Medical Center

Long Beach, California, United States

University of Florida

Gainesville, Florida, United States

The Cystic Fibrosis Institute

Glenview, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston Children's Hospital, Brigham & Women's Hospital

Boston, Massachusetts, United States

Billings Clinic

Billings, Montana, United States

New York Medical College at Westchester Medical Center

Hawthorne, New York, United States

UNC Marsico Clinical Research Center

Chapel Hill, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Utah

Salt Lake City, Utah, United States

Vermont Lung Center at the University of Vermont Medical Center

Colchester, Vermont, United States

Virginia Commonwealth University

Richmond, Virginia, United States

University of Calgary

Calgary, Alberta, Canada

St. Pauls' Hospital

Vancouver, British Columbia, Canada

McGill University Health Center

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

CX-280-202

Identifier Type: -

Identifier Source: org_study_id