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

Sponsor
Proteostasis Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03591094
Collaborator
(none)
40
Enrollment
26
Locations
3
Arms
5.9
Actual Duration (Months)
1.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 21, 2018
Actual Primary Completion Date :
Feb 18, 2019
Actual Study Completion Date :
Feb 18, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. Maximum plasma concentration (Cmax) [28 days]

  2. Time of Cmax (Tmax) [28 days]

  3. Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t) [28 days]

  4. Change in FEV1 over time [Baseline through Day 42]

  5. Change in sweat chloride over time [Baseline through Day 42]

Other Outcome Measures

  1. Change in nasal epithelial CFTR mRNA and protein expression over time [Baseline through Day 42]

  2. Change in CFQ-R over time [Baseline through Day 42]

  3. Cmax of PTI-428 metabolites, if applicable [28 days]

  4. Tmax of PTI-428 metabolites, if applicable [28 days]

  5. AUC0-t of PTI-428 metabolites, if applicable [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Proteostasis Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Proteostasis Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT03591094
Other Study ID Numbers:
  • PTI-428-06
First Posted:
Jul 18, 2018
Last Update Posted:
Feb 27, 2020
Last Verified:
Feb 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis

Study Results

No Results Posted as of Feb 27, 2020