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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02718495
• Other study ID #: PTI-428-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 19, 2016
• Est. completion date: November 28, 2017

Study information

• Verified date: March 2019
• Source: Proteostasis Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 28, 2017
• Est. primary completion date: November 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• PTI-428

• Placebo

Locations

Country	Name	City	State
Canada	Institut de Recherches Cliniques de Montreal	Montreal	Quebec
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec City	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Paul's Hospital Pacific Lung Research Center	Vancouver	British Columbia
Denmark	University of Copenhagen Rigshospitalet	Copenhagen
France	Groupe Hospitalier Pellegrin - Hôpital des Enfants	Bordeaux
France	Hôpital Cochin	Paris
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Frankfurt-Zentrum der Inneren Medizin	Frankfurt
United States	Central Florida Pulmonary Group	Altamonte Springs	Florida
United States	Universiy of Michigan Health System	Ann Arbor	Michigan
United States	St. Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho
United States	Childrens Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University Memorial Hospital	Chicago	Illinois
United States	Duke University Health System	Durham	North Carolina
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	Children's Lung Specialists	Las Vegas	Nevada
United States	University of Louisville	Louisville	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Quintiles Overland Park Phase 1 Unit	Overland Park	Kansas
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Proteostasis Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SAD: change in nasal epithelial CFTR mRNA and protein expression		Baseline through Day 7
Other	MAD: change in nasal epithelial CFTR mRNA and protein expression		Baseline through Day 14
Other	MAD: change in sweat chloride over time		Baseline through Day 14
Other	Part B and Part C Cohorts 2 and 3: change in nasal epithelial CFTR mRNA and protein expression		Baseline through Day 35
Other	Part B and Part C Cohorts 2 and 3: change in CFQ-R over time		Baseline through Day 28
Other	Part C Cohort 1: change in nasal epithelial CFTR mRNA and protein expression		Baseline through Day 49
Other	Part C Cohort 1: change in CFQ-R over time		Baseline through Day 42
Other	Part C Cohort 3: change in fecal elastase over time		Baseline through Day 35
Other	Part C Cohort 3: change in fecal calprotectin over time		Baseline through Day 35
Primary	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
Primary	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
Primary	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
Primary	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	SAD: apparent terminal half-life (t1/2) of single oral dose		Baseline through 72 hours post dose
Secondary	SAD: time to reach maximum plasma concentration (Tmax) of single oral dose		Baseline through 72 hours post dose
Secondary	SAD: maximum plasma concentration (Cmax) of single oral dose		Baseline through 72 hours post dose
Secondary	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
Secondary	MAD: t1/2 of multiple oral doses		Baseline through 24 hours post Day 7 dose
Secondary	MAD: Tmax of multiple oral doses		Baseline through 24 hours post Day 7 dose
Secondary	MAD: Cmax of multiple oral doses		Baseline through 24 hours post Day 7 dose
Secondary	MAD: AUC0-t of multiple oral doses		Baseline through 24 hours post Day 7 dose
Secondary	MAD: area under the concentration-time curve from time 0 to infinity (AUC0-8) of multiple oral doses		Baseline through 24 hours post Day 7 dose
Secondary	Part B and Part C Cohorts 2 and 3: t1/2 of multiple oral doses		Baseline through 24 hours post Day 28 dose
Secondary	Part B and Part C Cohorts 2 and 3: Tmax of multiple oral doses		Baseline through 24 hours post Day 28 dose
Secondary	Part B and Part C Cohorts 2 and 3: Cmax of multiple oral doses		Baseline through 24 hours post Day 28 dose
Secondary	Part B and Part C Cohorts 2 and 3: AUC0-t of multiple oral doses		Baseline through 24 hours post Day 28 dose
Secondary	Part B and Part C Cohorts 2 and 3: AUC0-8 of multiple oral doses		Baseline through 24 hours post Day 28 dose
Secondary	Part B and Part C Cohorts 2 and 3: change in forced expiratory volume in one second (FEV1) over time		Baseline through Day 35
Secondary	Part B and Part C Cohorts 2 and 3: change in sweat chloride over time		Baseline through Day 35
Secondary	Part B and Part C Cohorts 2 and 3: change in weight over time		Baseline through Day 35
Secondary	Part C Cohort 1: t1/2 of multiple oral doses		Baseline through Day 42
Secondary	Part C Cohort 1: Tmax of multiple oral doses		Baseline through Day 42
Secondary	Part C Cohort 1: Cmax of multiple oral doses		Baseline through Day 42
Secondary	Part C Cohort 1: AUC0-t of multiple oral doses		Baseline through Day 42
Secondary	Part C Cohort 1: AUC0-8 of multiple oral doses		Baseline through Day 42
Secondary	Part C Cohort 1: change in FEV1 over time		Baseline through Day 49
Secondary	Part C Cohort 1: change in sweat chloride over time		Baseline through Day 49
Secondary	Part C Cohort 1: change in weight over time		Baseline through Day 49

External Links

•   Information about the sponsor