Clinical trial NCT03591094: Study Assessing PTI-428 Safety, Tolerability, Pharmacokinetics and Effect in Subjects With Cystic Fibrosis
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect of PTI-428 in Subjects With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Proteostasis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study population is comprised of adult subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation and are currently receiving background treatment with tezacaftor/ivacaftor for a minimum of 1 month prior to Day 1. The planned sample size is approximately 40 subjects. 20 subjects will be assigned to PTI-428 dose level 1 or placebo and 20 subjects will be assigned to PTI-428 dose level 2 or placebo. At each dose level, subjects will be randomized at a 3:1 randomization ratio. Subjects will receive once daily oral doses of PTI-428 or placebo for 28 days, while the subjects continue to receive background treatment with tezacaftor/ivacaftor per product label. The study drug administration period will be followed by a 14-day safety follow-up period.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CF with the F508del/F508del genotype on record
* On tezacaftor/ivacaftor dosing for both label indication and per label dosing for a minimum of 1 month on Day 1
* Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
* Clinically stable with no significant changes in health status within 14 days of Day 1
* Non-smoker and non-tobacco user for a minimum of 28 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 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
* History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
* History of organ transplantation
* Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
* Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
* History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
* Pregnant or nursing women

Primary outcomes:
measure: Number of subjects with treatment-emergent adverse events (TEAEs)
timeFrame: Baseline through Day 42
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 days
measure: Time of Cmax (Tmax)
timeFrame: 28 days
measure: Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t)
timeFrame: 28 days
measure: Change in FEV1 over time
timeFrame: Baseline through Day 42
measure: Change in sweat chloride over time
timeFrame: Baseline through Day 42
Other outcomes:
measure: Change in nasal epithelial CFTR mRNA and protein expression over time
timeFrame: Baseline through Day 42
measure: Change in CFQ-R over time
timeFrame: Baseline through Day 42
measure: Cmax of PTI-428 metabolites, if applicable
timeFrame: 28 days
measure: Tmax of PTI-428 metabolites, if applicable
timeFrame: 28 days
measure: AUC0-t of PTI-428 metabolites, if applicable
timeFrame: 28 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Altamonte Springs
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa, Roy J and Lucille A Carver College of Medicine
state: Iowa
city: Louisville
country: United States
facility: Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine, University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Manchester
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler - Center for Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: