Back to resultsSafety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
PTI-808
Placebo
PTI-801
PTI-428
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
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
Sites / Locations
- Celerion
- Western General Hospital
- Queen Elizabeth University Hospital
- Medicines Evaluation Unit
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Arm Label
Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active
Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo
Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo
Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Outcomes
Primary Outcome Measures
Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.
Secondary Outcome Measures
Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Change in FEV1 over time
Full Information
NCT ID
NCT03500263
First Posted
April 9, 2018
Last Updated
March 31, 2020
Sponsor
Proteostasis Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03500263
Brief Title
Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 30, 2018 (Actual)
Primary Completion Date
March 13, 2019 (Actual)
Study Completion Date
March 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Proteostasis Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active
Arm Type
Active Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Arm Title
Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Arm Title
Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Arm Type
Active Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Arm Title
Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Arm Title
Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Arm Type
Active Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Arm Title
Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Intervention Type
Drug
Intervention Name(s)
PTI-808
Intervention Description
Active
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Intervention Type
Drug
Intervention Name(s)
PTI-801
Intervention Description
Active
Intervention Type
Drug
Intervention Name(s)
PTI-428
Intervention Description
Active
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.
Time Frame
Baseline through Day 21
Secondary Outcome Measure Information:
Title
Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Time Frame
Day 1 through 15
Title
Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Time Frame
Day 1 through 15
Title
Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
Time Frame
Day 1 through 15
Title
Change in FEV1 over time
Time Frame
Baseline through Day 21
Other Pre-specified Outcome Measures:
Title
Change in sweat chloride over time
Time Frame
Baseline through Day 21
Title
Change in weight over time
Time Frame
Baseline through Day 21
Title
Change in BMI over time
Time Frame
Baseline through Day 21
Title
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain results over time
Description
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.
Time Frame
Baseline through Day 21
Title
Change in nasal epithelial mRNA expression over time
Time Frame
Baseline through Day 21
Title
Change in nasal protein expression over time
Time Frame
Baseline through Day 21
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Celerion
City
Belfast
ZIP/Postal Code
BT9 6AD
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Facility Name
Queen Elizabeth University Hospital
City
Glasgow
ZIP/Postal Code
G514TF
Country
United Kingdom
Facility Name
Medicines Evaluation Unit
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
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