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

Sponsor
Proteostasis Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02718495
Collaborator
(none)
56
Enrollment
29
Locations
3
Arms
16.3
Actual Duration (Months)
1.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will consist of three arms: Part A, Part B, and Part C. Part A has two groups. The first group will enroll adult subjects with cystic fibrosis (CF) into a single ascending dose (SAD) treatment group. The second group will enroll adult subjects with CF, including those on background treatment with ORKAMBI® and those not on a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, into a multiple ascending dose (MAD) treatment group. Part B will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months into a Phase II treatment group consisting of two cohorts. Part C will enroll adult subjects with CF, including those on background treatment with KALYDECO® and those not on a CFTR modulator, into a Phase II treatment group consisting of three cohorts. Approximately 136 subjects will be enrolled.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

PART A The SAD treatment group is comprised of 3 cohorts where subjects will be randomized to either PTI-428 or placebo. Following the conclusion of at least 3 SAD treatment groups, a set of adult subjects diagnosed with CF will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 cohorts. MAD Cohort 1 will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months at the time of randomization. MAD Cohorts 2 and 3 will enroll adult subjects with CF who are not currently on any background therapies. Subjects in all MAD cohorts will be randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a total of 7 Days.

PART B Following the conclusion of MAD Cohort 1, a set of adult subjects diagnosed with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months will participate in Part B. The Part B Phase II treatment group is comprised of 2 cohorts where subjects will be randomized to either PTI-428 or placebo. Each dose will be administered QD for a total of 28 days.

PART C Following the conclusion of Part B Phase II, a set of adult subjects diagnosed with CF will participate in Part C. The Part C Phase II treatment group is comprised of 3 cohorts. Part C Cohort 1 will enroll adult subjects with CF who are eligible to take, but not currently taking, ORKAMBI® in accordance with the approved label. Part C Cohort 2 will enroll adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3 months at the time of randomization. Part C Cohort 3 will enroll adult subjects with CF who are not currently on any background therapies and are pancreatic sufficient. Each PTI-428 or placebo dose will be administered QD for a total of 28 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
56 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase I/II, Multi-center, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis
Actual Study Start Date :
Jul 19, 2016
Actual Primary Completion Date :
Nov 28, 2017
Actual Study Completion Date :
Nov 28, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Part A

Part A consists of two treatment groups, SAD and MAD. Both treatment groups will consist of 3 cohorts. In SAD, subjects will receive a single dose of PTI-428 or placebo. In MAD, subjects will receive once daily dosing of PTI-428 or placebo for 7 days.

Drug: PTI-428

Drug: Placebo
Placebo Comparator: Part B

Part B will consist of 2 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.

Drug: PTI-428

Drug: Placebo
Placebo Comparator: Part C

Part C will consist of 3 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.

Drug: PTI-428

Drug: Placebo

Outcome Measures

Primary Outcome Measures

  1. SAD: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Baseline to Day 7]

  2. MAD: safety and tolerability as assessed by adverse events, pulomonary function tests, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Baseline to Day 14]

  3. Part B and Part C Cohorts 2 and 3: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Baseline to Day 35]

  4. Part C Cohort 1: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Baseline to Day 49]

Secondary Outcome Measures

  1. SAD: apparent terminal half-life (t1/2) of single oral dose [Baseline through 72 hours post dose]

  2. SAD: time to reach maximum plasma concentration (Tmax) of single oral dose [Baseline through 72 hours post dose]

  3. SAD: maximum plasma concentration (Cmax) of single oral dose [Baseline through 72 hours post dose]

  4. SAD: area under the concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of single oral dose [Baseline through 72 hours post dose]

  5. MAD: t1/2 of multiple oral doses [Baseline through 24 hours post Day 7 dose]

  6. MAD: Tmax of multiple oral doses [Baseline through 24 hours post Day 7 dose]

  7. MAD: Cmax of multiple oral doses [Baseline through 24 hours post Day 7 dose]

  8. MAD: AUC0-t of multiple oral doses [Baseline through 24 hours post Day 7 dose]

  9. MAD: area under the concentration-time curve from time 0 to infinity (AUC0-∞) of multiple oral doses [Baseline through 24 hours post Day 7 dose]

  10. Part B and Part C Cohorts 2 and 3: t1/2 of multiple oral doses [Baseline through 24 hours post Day 28 dose]

  11. Part B and Part C Cohorts 2 and 3: Tmax of multiple oral doses [Baseline through 24 hours post Day 28 dose]

  12. Part B and Part C Cohorts 2 and 3: Cmax of multiple oral doses [Baseline through 24 hours post Day 28 dose]

  13. Part B and Part C Cohorts 2 and 3: AUC0-t of multiple oral doses [Baseline through 24 hours post Day 28 dose]

  14. Part B and Part C Cohorts 2 and 3: AUC0-∞ of multiple oral doses [Baseline through 24 hours post Day 28 dose]

  15. Part B and Part C Cohorts 2 and 3: change in forced expiratory volume in one second (FEV1) over time [Baseline through Day 35]

  16. Part B and Part C Cohorts 2 and 3: change in sweat chloride over time [Baseline through Day 35]

  17. Part B and Part C Cohorts 2 and 3: change in weight over time [Baseline through Day 35]

  18. Part C Cohort 1: t1/2 of multiple oral doses [Baseline through Day 42]

  19. Part C Cohort 1: Tmax of multiple oral doses [Baseline through Day 42]

  20. Part C Cohort 1: Cmax of multiple oral doses [Baseline through Day 42]

  21. Part C Cohort 1: AUC0-t of multiple oral doses [Baseline through Day 42]

  22. Part C Cohort 1: AUC0-∞ of multiple oral doses [Baseline through Day 42]

  23. Part C Cohort 1: change in FEV1 over time [Baseline through Day 49]

  24. Part C Cohort 1: change in sweat chloride over time [Baseline through Day 49]

  25. Part C Cohort 1: change in weight over time [Baseline through Day 49]

Other Outcome Measures

  1. SAD: change in nasal epithelial CFTR mRNA and protein expression [Baseline through Day 7]

  2. MAD: change in nasal epithelial CFTR mRNA and protein expression [Baseline through Day 14]

  3. MAD: change in sweat chloride over time [Baseline through Day 14]

  4. Part B and Part C Cohorts 2 and 3: change in nasal epithelial CFTR mRNA and protein expression [Baseline through Day 35]

  5. Part B and Part C Cohorts 2 and 3: change in CFQ-R over time [Baseline through Day 28]

  6. Part C Cohort 1: change in nasal epithelial CFTR mRNA and protein expression [Baseline through Day 49]

  7. Part C Cohort 1: change in CFQ-R over time [Baseline through Day 42]

  8. Part C Cohort 3: change in fecal elastase over time [Baseline through Day 35]

  9. Part C Cohort 3: change in fecal calprotectin over time [Baseline through Day 35]

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.

  • Forced expiratory volume in 1 second (FEV1) 40-90% predicted.

  • Non-smoker and non-tobacco user for a minimum of 30 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 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.

  • History of cancer within the past five years (excluding cervical CIS with curative therapy for at least one year prior to screening and non-melanoma skin cancer).

  • History of organ transplantation.

  • Any sinopulmonary infection or CF exacerbation requiring a change or addition of medication (including antibiotics) within 1 month of Study Day 1 or any other clinically significant infection as determined by the investigator within 1 month of Day 1.

  • History of alcohol or drug abuse or dependence within 12 months of screening as determined by the Investigator.

  • Male and female of child-bearing potential, unless they are using highly effective methods of contraception during participation in the clinical study and for 4 weeks after termination from study.

  • Pregnant or nursing women.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stanford University Medical Center Stanford California United States 94305
2 Central Florida Pulmonary Group Altamonte Springs Florida United States 32803
3 University of Florida College of Medicine Gainesville Florida United States 32610
4 St. Luke's Cystic Fibrosis Center of Idaho Boise Idaho United States 83712
5 Northwestern University Memorial Hospital Chicago Illinois United States 60611
6 University of Iowa Iowa City Iowa United States 52242
7 University of Kansas Medical Center Research Institute, Inc. Kansas City Kansas United States 66160
8 Quintiles Overland Park Phase 1 Unit Overland Park Kansas United States 66211
9 University of Louisville Louisville Kentucky United States 40202
10 Massachusetts General Hospital Boston Massachusetts United States 02114
11 Childrens Hospital Boston Boston Massachusetts United States 02115
12 Universiy of Michigan Health System Ann Arbor Michigan United States 48109
13 Mayo Clinic Rochester Minnesota United States 55905
14 Children's Lung Specialists Las Vegas Nevada United States 89107
15 Duke University Health System Durham North Carolina United States 27710
16 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
17 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
18 Drexel University College of Medicine Philadelphia Pennsylvania United States 19107
19 Medical University of South Carolina Charleston South Carolina United States 29425
20 Vanderbilt University Medical Center Nashville Tennessee United States 37232
21 St. Paul's Hospital Pacific Lung Research Center Vancouver British Columbia Canada V6Z 1Y6
22 St. Michael's Hospital Toronto Ontario Canada M5B 1W8
23 Institut de Recherches Cliniques de Montreal Montreal Quebec Canada H2X 0A9
24 Institut Universitaire de Cardiologie et de Pneumologie de Quebec Quebec City Quebec Canada G1V 4G5
25 University of Copenhagen Rigshospitalet Copenhagen Denmark 2100
26 Groupe Hospitalier Pellegrin - Hôpital des Enfants Bordeaux France 33076
27 Hôpital Cochin Paris France 75014
28 Charite - Campus Virchow-Klinikum Berlin Germany 10117
29 Universitaetsklinikum Frankfurt-Zentrum der Inneren Medizin Frankfurt Germany 60590

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:
NCT02718495
Other Study ID Numbers:
  • PTI-428-01
First Posted:
Mar 24, 2016
Last Update Posted:
Mar 21, 2019
Last Verified:
Mar 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis

Study Results

No Results Posted as of Mar 21, 2019