Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

A Phase 1 / 2, Randomized, Double-Blind, Placebo-Controlled Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03500263
• Other study ID #: PTI-808-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 30, 2018
• Est. completion date: March 13, 2019

Study information

• Verified date: March 2020
• Source: Proteostasis Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 13, 2019
• Est. primary completion date: March 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• PTI-808
Active
• Placebo
Placebo
• PTI-801
Active
• PTI-428
Active
• Placebo
Placebo

Locations

Country	Name	City	State
United Kingdom	Celerion	Belfast
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Proteostasis Therapeutics, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in sweat chloride over time		Baseline through Day 21
Other	Change in weight over time		Baseline through Day 21
Other	Change in BMI over time		Baseline through Day 21
Other	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain results over time	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.	Baseline through Day 21
Other	Change in nasal epithelial mRNA expression over time		Baseline through Day 21
Other	Change in nasal protein expression over time		Baseline through Day 21
Primary	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	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
Secondary	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
Secondary	Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)		Day 1 through 15
Secondary	Change in FEV1 over time		Baseline through Day 21

External Links

•   Information about the sponsor