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

NCT02718495 | Completed Phase 1 DMC

• 1 other identifier: PTI-428-01
• Study Type: interventional
• Target: 56
• Locations: 5 countries
• Sites: 29

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (25)

• SAD: apparent terminal half-life (t1/2) of single oral dose

  Baseline through 72 hours post dose

• SAD: time to reach maximum plasma concentration (Tmax) of single oral dose

  Baseline through 72 hours post dose

• SAD: maximum plasma concentration (Cmax) of single oral dose

  Baseline through 72 hours post dose

• 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

• MAD: t1/2 of multiple oral doses

  Baseline through 24 hours post Day 7 dose

Other Outcomes (9)

• SAD: change in nasal epithelial CFTR mRNA and protein expression

  Baseline through Day 7

• MAD: change in nasal epithelial CFTR mRNA and protein expression

  Baseline through Day 14

• MAD: change in sweat chloride over time

  Baseline through Day 14

Study Arms (3)

Part A

PLACEBO COMPARATOR

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

Part B

PLACEBO COMPARATOR

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

Part C

PLACEBO COMPARATOR

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

Interventions

PTI-428 DRUG

Part A; Part B; Part C

Placebo DRUG

Part A; Part B; Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Proteostasis Therapeutics, Inc.: lead

Study Sites (29)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Central Florida Pulmonary Group

Altamonte Springs, Florida, 32803, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

St. Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, 83712, United States

Location

Northwestern University Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Quintiles Overland Park Phase 1 Unit

Overland Park, Kansas, 66211, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Childrens Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Universiy of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Children's Lung Specialists

Las Vegas, Nevada, 89107, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

St. Paul's Hospital Pacific Lung Research Center

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Institut de Recherches Cliniques de Montreal

Montreal, Quebec, H2X 0A9, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, G1V 4G5, Canada

Location

University of Copenhagen Rigshospitalet

Copenhagen, 2100, Denmark

Location

Groupe Hospitalier Pellegrin - Hôpital des Enfants

Bordeaux, 33076, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Charite - Campus Virchow-Klinikum

Berlin, 10117, Germany

Location

Universitaetsklinikum Frankfurt-Zentrum der Inneren Medizin

Frankfurt, 60590, Germany

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: March 24, 2016
• Study Start: July 19, 2016
• Primary Completion: November 28, 2017
• Study Completion: November 28, 2017
• Last Updated: March 21, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (4); US (20); DK (1); FR (2); DE (2)