Clinical trial NCT04279769: Study to Evaluate the Safety of CB-280 in Patients With Cystic Fibrosis
Official title: A Phase 1b Randomized, Double-blind, Placebo-Controlled Trial to Evaluate the Safety of CB-280 in Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Keywords: Arginase inhibitor
CB-280
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2020-02-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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)

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: 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)
timeFrame: Start of treatment to Day 28
Secondary outcomes:
measure: Pharmacokinetics of plasma CB-280 measured by Peak Plasma Concentration (Cmax)
timeFrame: Day 14
measure: 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)
timeFrame: Day 14
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Glenview
country: United States
facility: The Cystic Fibrosis Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital, Brigham & Women's Hospital
state: Massachusetts
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Hawthorne
country: United States
facility: New York Medical College at Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Marsico Clinical Research Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Hershey
country: United States
facility: Hershey Medical Center Pennsylvania State University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center at the University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: St. Pauls' Hospital
state: British Columbia
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: Calithera Bioscience
name: Emil T Kuriakose, MD
role: STUDY_DIRECTOR
References: