Cystic Fibrosis
Conditions
Keywords
Arginase inhibitor, CB-280
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.
Interventions
DRUGPlacebos
Placebo oral capsule administrated twice daily at the assigned dose level for 14 days
DRUGCB-280
CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
Sponsors
Calithera Biosciences, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Pharmacokinetics of plasma CB-280 measured by Peak Plasma Concentration (Cmax) | Day 14 |
| 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 |
Countries
Canada, United States
Outcome results
None listed