Cystic Fibrosis
Conditions
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.
Interventions
DRUGPTI-428
Active
DRUGPlacebo
Placebo
Sponsors
Proteostasis Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with treatment-emergent adverse events (TEAEs) | Baseline through Day 42 | Safety and tolerability will be assessed by adverse events (AEs), safety labs, electrocardiograms (ECGs), physical examinations and vital signs. |
Secondary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax) | 28 days |
| Time of Cmax (Tmax) | 28 days |
| Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t) | 28 days |
| Change in FEV1 over time | Baseline through Day 42 |
| Change in sweat chloride over time | Baseline through Day 42 |
Other
| Measure | Time frame |
|---|---|
| Change in CFQ-R over time | Baseline through Day 42 |
| Cmax of PTI-428 metabolites, if applicable | 28 days |
| Tmax of PTI-428 metabolites, if applicable | 28 days |
| AUC0-t of PTI-428 metabolites, if applicable | 28 days |
| Change in nasal epithelial CFTR mRNA and protein expression over time | Baseline through Day 42 |
Countries
United States
Outcome results
None listed