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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: CB-280; Drug: Placebos

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Calithera Biosciences, Inc
• Investigators: Study Director: Emil T Kuriakose, MD, Calithera Bioscience

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 3, 2020
• Primary Completion (ACTUAL): November 23, 2021
• Study Completion (ACTUAL): November 23, 2021

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (ACTUAL): February 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Arginase inhibitor; CB-280
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: CX-280-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No