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

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect of PTI-428 in Subjects With Cystic Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: PTI-428

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Central Florida Pulmonary Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Peoria, Illinois, United States, 61637
      • Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Roy J and Lucille A Carver College of Medicine
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine, University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Hampshire
    • Manchester, New Hampshire, United States, 03104
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science Center at Tyler - Center for Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: PTI-428 dose level 1	Drug: PTI-428; Active
ACTIVE_COMPARATOR: PTI-428 dose level 2	Drug: PTI-428; Active
PLACEBO_COMPARATOR: Placebo PTI-428	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment-emergent adverse events (TEAEs)	Safety and tolerability will be assessed by adverse events (AEs), safety labs, electrocardiograms (ECGs), physical examinations and vital signs.	Baseline through Day 42

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Change in nasal epithelial CFTR mRNA and protein expression over time	Baseline through Day 42
Change in CFQ-R over time	Baseline through Day 42
Cmax of PTI-428 metabolites, if applicable	28 days
Tmax of PTI-428 metabolites, if applicable	28 days
AUC0-t of PTI-428 metabolites, if applicable	28 days

Collaborators and Investigators

• Sponsor: Proteostasis Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 21, 2018
• Primary Completion (ACTUAL): February 18, 2019
• Study Completion (ACTUAL): February 18, 2019

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: July 6, 2018
• First Posted (ACTUAL): July 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• 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: PTI-428-06

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