Cystic Fibrosis
Conditions
Brief summary
The study is a randomized, double-blind, placebo-controlled, study that will be conducted at multiple centers in subjects with Cystic Fibrosis (CF) who are either homozygous for the F508del mutation or heterozygous with at least copy of the F508del mutation.
Detailed description
Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment into subsequent cohorts will be based upon review and approval by the Safety Review Committee (SRC).
Sponsors
Proteostasis Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohorts 1,2 and 4: A Confirmed diagnosis of CF with the F508del/F508del CFTR genotype on record, along with clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities * Cohort 3 only: Confirmed diagnosis of CF with at least one copy of the F508del CFTR mutation on record, along with clinical findings consistent with CF, such as chronic sinopulmonary disease or gastrointestinal / nutritional abnormalities * Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive * Non-smoker and non-tobacco user for a minimum of 30 days prior to screening * Cohort 3 only: A sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine iontophoresis (as documented in the subject's medical record or as confirmed at the screening visit)
Exclusion criteria
* Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs * 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 * 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 |
|---|---|
| Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs. | Baseline through Day 21 |
Secondary
| Measure | Time frame |
|---|---|
| Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) | Day 1 through 15 |
| Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) | Day 1 through 15 |
| Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) | Day 1 through 15 |
| Change in FEV1 over time | Baseline through Day 21 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in sweat chloride over time | Baseline through Day 21 | — |
| Change in nasal protein expression over time | Baseline through Day 21 | — |
| Change in weight over time | Baseline through Day 21 | — |
| Change in BMI over time | Baseline through Day 21 | — |
| Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain results over time | Baseline through Day 21 | Disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms. Developed specifically for use in patients with a diagnosis of cystic fibrosis. Scaling of items: 5 distinct 4-point Likert scales (e.g., always/often/ sometime/never) Scoring: Scores for each HRQoL domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health. |
| Change in nasal epithelial mRNA expression over time | Baseline through Day 21 | — |
Countries
United Kingdom
Outcome results
None listed