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

Cystic Fibrosis Clinical Trial

Official title:

A Phase 1b Randomized, Double-blind, Placebo-Controlled Trial to Evaluate the Safety of CB-280 in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04279769
• Other study ID #: CX-280-202
• Status: Completed
• Phase: Phase 1
• Start date: July 3, 2020
• Est. completion date: November 23, 2021

Study information

• Verified date: April 2022
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 23, 2021
• Est. primary completion date: November 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• CB-280
CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
• Placebos
Placebo oral capsule administrated twice daily at the assigned dose level for 14 days

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McGill University Health Center	Montréal	Quebec
Canada	St. Pauls' Hospital	Vancouver	British Columbia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	Boston Children's Hospital, Brigham & Women's Hospital	Boston	Massachusetts
United States	UNC Marsico Clinical Research Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Vermont Lung Center at the University of Vermont Medical Center	Colchester	Vermont
United States	University of Florida	Gainesville	Florida
United States	The Cystic Fibrosis Institute	Glenview	Illinois
United States	New York Medical College at Westchester Medical Center	Hawthorne	New York
United States	Hershey Medical Center Pennsylvania State University	Hershey	Pennsylvania
United States	Indiana University	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the safety and tolerability of CB-280 in adult cystic fibrosis patients: incidence and severity of adverse event (AEs) assessed by Common Terminology Criteria for Adverse Events, version 5 (CTCAE v5.0)		Start of treatment to Day 28
Secondary	Pharmacokinetics of plasma CB-280 measured by Peak Plasma Concentration (Cmax)		Day 14
Secondary	Pharmacokinetics of plasma CB-280 measured by area under the plasma concentration versus time curve, from time 0 to the last observed non-zero concentration (AUC 0-t)		Day 14