Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis
- Registration Number
- NCT02718495
- Lead Sponsor
- Proteostasis Therapeutics, Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A Placebo 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. Part B Placebo Part B will consist of 2 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days. Part C Placebo Part C will consist of 3 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days. Part A PTI-428 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. Part C PTI-428 Part C will consist of 3 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days. Part B PTI-428 Part B will consist of 2 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.
- Primary Outcome Measures
Name Time Method 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 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
- Secondary Outcome Measures
Name Time Method 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 MAD: Tmax of multiple oral doses Baseline through 24 hours post Day 7 dose MAD: Cmax of multiple oral doses Baseline through 24 hours post Day 7 dose MAD: AUC0-t of multiple oral doses Baseline through 24 hours post Day 7 dose 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 Part B and Part C Cohorts 2 and 3: t1/2 of multiple oral doses Baseline through 24 hours post Day 28 dose Part B and Part C Cohorts 2 and 3: Tmax of multiple oral doses Baseline through 24 hours post Day 28 dose Part B and Part C Cohorts 2 and 3: Cmax of multiple oral doses Baseline through 24 hours post Day 28 dose Part B and Part C Cohorts 2 and 3: AUC0-t of multiple oral doses Baseline through 24 hours post Day 28 dose Part B and Part C Cohorts 2 and 3: AUC0-∞ of multiple oral doses Baseline through 24 hours post Day 28 dose Part B and Part C Cohorts 2 and 3: change in forced expiratory volume in one second (FEV1) over time Baseline through Day 35 Part B and Part C Cohorts 2 and 3: change in sweat chloride over time Baseline through Day 35 Part B and Part C Cohorts 2 and 3: change in weight over time Baseline through Day 35 Part C Cohort 1: t1/2 of multiple oral doses Baseline through Day 42 Part C Cohort 1: Tmax of multiple oral doses Baseline through Day 42 Part C Cohort 1: Cmax of multiple oral doses Baseline through Day 42 Part C Cohort 1: AUC0-t of multiple oral doses Baseline through Day 42 Part C Cohort 1: AUC0-∞ of multiple oral doses Baseline through Day 42 Part C Cohort 1: change in FEV1 over time Baseline through Day 49 Part C Cohort 1: change in sweat chloride over time Baseline through Day 49 Part C Cohort 1: change in weight over time Baseline through Day 49
Trial Locations
- Locations (29)
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Northwestern University Memorial Hospital
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Children's Lung Specialists
🇺🇸Las Vegas, Nevada, United States
St. Paul's Hospital Pacific Lung Research Center
🇨🇦Vancouver, British Columbia, Canada
Childrens Hospital Boston
🇺🇸Boston, Massachusetts, United States
St. Luke's Cystic Fibrosis Center of Idaho
🇺🇸Boise, Idaho, United States
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Universitaetsklinikum Frankfurt-Zentrum der Inneren Medizin
🇩🇪Frankfurt, Germany
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
🇨🇦Quebec City, Quebec, Canada
Central Florida Pulmonary Group
🇺🇸Altamonte Springs, Florida, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Kansas City, Kansas, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Quintiles Overland Park Phase 1 Unit
🇺🇸Overland Park, Kansas, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Institut de Recherches Cliniques de Montreal
🇨🇦Montreal, Quebec, Canada
University of Copenhagen Rigshospitalet
🇩🇰Copenhagen, Denmark
Groupe Hospitalier Pellegrin - Hôpital des Enfants
🇫🇷Bordeaux, France
Hôpital Cochin
🇫🇷Paris, France
Universiy of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States