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

NCT ID: NCT02718495

Last Updated: 2019-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-19

Study Completion Date

2017-11-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

PTI-428

Intervention Type DRUG

Placebo

Intervention Type DRUG

Part B

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

Group Type PLACEBO_COMPARATOR

PTI-428

Intervention Type DRUG

Placebo

Intervention Type DRUG

Part C

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

Group Type PLACEBO_COMPARATOR

PTI-428

Intervention Type DRUG

Placebo

Intervention Type DRUG

Interventions

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PTI-428

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Proteostasis Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Stanford University Medical Center

Stanford, California, United States

Site Status

Central Florida Pulmonary Group

Altamonte Springs, Florida, United States

Site Status

University of Florida College of Medicine

Gainesville, Florida, United States

Site Status

St. Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States

Site Status

Northwestern University Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Site Status

Quintiles Overland Park Phase 1 Unit

Overland Park, Kansas, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Childrens Hospital Boston

Boston, Massachusetts, United States

Site Status

Universiy of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Children's Lung Specialists

Las Vegas, Nevada, United States

Site Status

Duke University Health System

Durham, North Carolina, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

St. Paul's Hospital Pacific Lung Research Center

Vancouver, British Columbia, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Institut de Recherches Cliniques de Montreal

Montreal, Quebec, Canada

Site Status

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, Canada

Site Status

University of Copenhagen Rigshospitalet

Copenhagen, , Denmark

Site Status

Groupe Hospitalier Pellegrin - Hôpital des Enfants

Bordeaux, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Charite - Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Universitaetsklinikum Frankfurt-Zentrum der Inneren Medizin

Frankfurt, , Germany

Site Status

Countries

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United States Canada Denmark France Germany

Other Identifiers

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PTI-428-01

Identifier Type: -

Identifier Source: org_study_id

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