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

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT04279769

Collaborator

(none)

Enrollment

Locations

Arms

16.7

Actual Duration (Months)

1.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: CB-280 Drug: Placebos	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 3, 2020

Actual Primary Completion Date :

Nov 23, 2021

Actual Study Completion Date :

Nov 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 CB-280 twice daily at 50 mg for 14 days	Drug: CB-280 CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
Experimental: Cohort 2 CB-280 twice daily at 100 mg for 14 days	Drug: CB-280 CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
Experimental: Cohort 3 CB-280 twice daily at 200 mg for 14 days	Drug: CB-280 CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
Experimental: Cohort 4 CB-280 twice daily at 400 mg for 14 days	Drug: CB-280 CB-280, oral capsule administered twice daily at the assigned dose level for 14 days
Placebo Comparator: Placebo Placebo twice daily for 14 days	Drug: Placebos Placebo oral capsule administrated twice daily at the assigned dose level for 14 days

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written Informed Consent in accordance with federal, local, and institutional guidelines
Confirmed diagnosis of cystic fibrosis
Male or female subjects ≥ 18 years on the date of informed consent
Percent predicted FEV1 of 40-90% at screening per Global Lung Function Initiative (GLI) equation
Clinically stable with no significant changes in health status within 28 days prior to Day 1
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
Stable cystic fibrosis medication regimen for at least 28 days inclusive of CFTR modulators prior to Day 1
Hemoglobin > 10 g/dL at screening
Glomerular filtration rate > 50 mL/min/1.73 m2 at screening
Normal liver function at screening

Exclusion Criteria:

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
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)
Unable to receive study medication per os (PO)
Females who are pregnant, have a positive pregnancy test at screening, or are nursing (lactating)

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
3	University of Florida	Gainesville	Florida	United States	32610
4	The Cystic Fibrosis Institute	Glenview	Illinois	United States	60025
5	Indiana University	Indianapolis	Indiana	United States	46202
6	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
7	Johns Hopkins University	Baltimore	Maryland	United States	21287
8	Boston Children's Hospital, Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
9	Billings Clinic	Billings	Montana	United States	59101
10	New York Medical College at Westchester Medical Center	Hawthorne	New York	United States	10532
11	UNC Marsico Clinical Research Center	Chapel Hill	North Carolina	United States	27514
12	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
13	Hershey Medical Center Pennsylvania State University	Hershey	Pennsylvania	United States	17033
14	Medical University of South Carolina	Charleston	South Carolina	United States	29425
15	University of Utah	Salt Lake City	Utah	United States	84132
16	Vermont Lung Center at the University of Vermont Medical Center	Colchester	Vermont	United States	05446
17	Virginia Commonwealth University	Richmond	Virginia	United States	23219
18	University of Calgary	Calgary	Alberta	Canada	T2N 4N1
19	St. Pauls' Hospital	Vancouver	British Columbia	Canada	V6Z1Y6
20	McGill University Health Center	Montréal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

Calithera Biosciences, Inc

Investigators

Study Director: Emil T Kuriakose, MD, Calithera Bioscience

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Calithera Biosciences, Inc

ClinicalTrials.gov Identifier:

NCT04279769

Other Study ID Numbers:

CX-280-202

First Posted:

Feb 21, 2020

Last Update Posted:

Apr 13, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Calithera Biosciences, Inc

Arginase inhibitor

CB-280

Additional relevant MeSH terms:

Cystic Fibrosis

Fibrosis

Study Results

No Results Posted as of Apr 13, 2022