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Study Assessing PTI-428 Safety, Tolerability, Pharmacokinetics and Effect in Subjects With Cystic Fibrosis

Phase 2
Completed
Conditions
Cystic Fibrosis
Interventions
Drug: Placebo
Registration Number
NCT03591094
Lead Sponsor
Proteostasis Therapeutics, Inc.
Brief Summary

The study population is comprised of adult subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation and are currently receiving background treatment with tezacaftor/ivacaftor for a minimum of 1 month prior to Day 1. The planned sample size is approximately 40 subjects. 20 subjects will be assigned to PTI-428 dose level 1 or placebo and 20 subjects will be assigned to PTI-428 dose level 2 or placebo. At each dose level, subjects will be randomized at a 3:1 randomization ratio. Subjects will receive once daily oral doses of PTI-428 or placebo for 28 days, while the subjects continue to receive background treatment with tezacaftor/ivacaftor per product label. The study drug administration period will be followed by a 14-day safety follow-up period.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Confirmed diagnosis of CF with the F508del/F508del genotype on record
  • On tezacaftor/ivacaftor dosing for both label indication and per label dosing for a minimum of 1 month on Day 1
  • Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
  • Clinically stable with no significant changes in health status within 14 days of Day 1
  • Non-smoker and non-tobacco user for a minimum of 28 days prior to screening and for the duration of the study
Exclusion Criteria
  • Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
  • History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
  • History of organ transplantation
  • Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
  • Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
  • History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
  • Pregnant or nursing women

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PTI-428 dose level 2PTI-428-
Placebo PTI-428Placebo-
PTI-428 dose level 1PTI-428-
Primary Outcome Measures
NameTimeMethod
Number of subjects with treatment-emergent adverse events (TEAEs)Baseline through Day 42

Safety and tolerability will be assessed by adverse events (AEs), safety labs, electrocardiograms (ECGs), physical examinations and vital signs.

Secondary Outcome Measures
NameTimeMethod
Time of Cmax (Tmax)28 days
Change in FEV1 over timeBaseline through Day 42
Change in sweat chloride over timeBaseline through Day 42
Maximum plasma concentration (Cmax)28 days
Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t)28 days

Trial Locations

Locations (26)

New York Medical College

🇺🇸

Valhalla, New York, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Arizona

🇺🇸

Tucson, Arizona, United States

University of Iowa, Roy J and Lucille A Carver College of Medicine

🇺🇸

Iowa City, Iowa, United States

Stanford University

🇺🇸

Stanford, California, United States

Maine Medical Center

🇺🇸

Portland, Maine, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit

🇺🇸

Louisville, Kentucky, United States

Mount Sinai Beth Israel

🇺🇸

New York, New York, United States

National Jewish Health

🇺🇸

Denver, Colorado, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Akron Children's Hospital

🇺🇸

Akron, Ohio, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center

🇺🇸

Peoria, Illinois, United States

Central Florida Pulmonary Group

🇺🇸

Altamonte Springs, Florida, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Manchester, New Hampshire, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

The University of Texas Health Science Center at Tyler - Center for Clinical Research

🇺🇸

Tyler, Texas, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Michigan Medicine, University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

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