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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PTI-428
Placebo
Sponsored by
Proteostasis Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University of Arizona
  • Stanford University
  • National Jewish Health
  • Central Florida Pulmonary Group
  • Northwestern University
  • Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
  • University of Iowa, Roy J and Lucille A Carver College of Medicine
  • Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit
  • Maine Medical Center
  • Massachusetts General Hospital
  • Boston Children's Hospital
  • Michigan Medicine, University of Michigan
  • University of Minnesota
  • Children's Mercy Hospital
  • Dartmouth Hitchcock Medical Center
  • Mount Sinai Beth Israel
  • Columbia University Medical Center
  • New York Medical College
  • Duke University Medical Center
  • Akron Children's Hospital
  • Nationwide Children's Hospital
  • Children's Hospital of Pittsburgh of UPMC
  • Medical University of South Carolina
  • The University of Texas Health Science Center at Tyler - Center for Clinical Research
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

PTI-428 dose level 1

PTI-428 dose level 2

Placebo PTI-428

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Maximum plasma concentration (Cmax)
Time of Cmax (Tmax)
Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t)
Change in FEV1 over time
Change in sweat chloride over time

Full Information

First Posted
July 6, 2018
Last Updated
February 25, 2020
Sponsor
Proteostasis Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03591094
Brief Title
Study Assessing PTI-428 Safety, Tolerability, Pharmacokinetics and Effect in Subjects With Cystic Fibrosis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
August 21, 2018 (Actual)
Primary Completion Date
February 18, 2019 (Actual)
Study Completion Date
February 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Proteostasis Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PTI-428 dose level 1
Arm Type
Active Comparator
Arm Title
PTI-428 dose level 2
Arm Type
Active Comparator
Arm Title
Placebo PTI-428
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PTI-428
Intervention Description
Active
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Number of subjects with treatment-emergent adverse events (TEAEs)
Description
Safety and tolerability will be assessed by adverse events (AEs), safety labs, electrocardiograms (ECGs), physical examinations and vital signs.
Time Frame
Baseline through Day 42
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax)
Time Frame
28 days
Title
Time of Cmax (Tmax)
Time Frame
28 days
Title
Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t)
Time Frame
28 days
Title
Change in FEV1 over time
Time Frame
Baseline through Day 42
Title
Change in sweat chloride over time
Time Frame
Baseline through Day 42
Other Pre-specified Outcome Measures:
Title
Change in nasal epithelial CFTR mRNA and protein expression over time
Time Frame
Baseline through Day 42
Title
Change in CFQ-R over time
Time Frame
Baseline through Day 42
Title
Cmax of PTI-428 metabolites, if applicable
Time Frame
28 days
Title
Tmax of PTI-428 metabolites, if applicable
Time Frame
28 days
Title
AUC0-t of PTI-428 metabolites, if applicable
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Central Florida Pulmonary Group
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32701
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
University of Iowa, Roy J and Lucille A Carver College of Medicine
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Michigan Medicine, University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03104
Country
United States
Facility Name
Mount Sinai Beth Israel
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
The University of Texas Health Science Center at Tyler - Center for Clinical Research
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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