Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis on KALYDECO® as Background Therapy

• ClinicalTrials.gov Identifier: NCT03258424
• Recruitment Status: Completed
• First Posted: August 23, 2017
• Last Update Posted: March 26, 2020
• Sponsor: Proteostasis Therapeutics, Inc.
• Information provided by (Responsible Party): Proteostasis Therapeutics, Inc.

Study Description

Brief Summary:

The trial will consist of a single treatment group enrolling adult subjects with CF on background therapy with KALYDECO®. Approximately 16 subjects will be enrolled.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: PTI-428; Drug: Placebo	Phase 1

Detailed Description:

The single treatment group will enroll adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3 months at the time of randomization. Subjects will be randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a total of 14 Days. The subjects will continue treatment with KALYDECO® throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase I, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis.
• Actual Study Start Date: July 28, 2017
• Actual Primary Completion Date: October 3, 2018
• Actual Study Completion Date: October 3, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: PTI-428; Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.	Drug: PTI-428; PTI-428 or placebo will be given QD for 14 days.
Placebo Comparator: Placebo; Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.	Drug: Placebo; PTI-428 or placebo will be given QD for 14 days.

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability as assessed by adverse events, safety labs, electrocardiograms (ECGs), physical examinations, and vital signs [ Time Frame: Baseline through Day 21 ]

Secondary Outcome Measures :

1. t1/2 of multiple oral doses [ Time Frame: Baseline through Day 14 ]
2. Tmax of multiple oral doses [ Time Frame: Baseline through Day 14 ]
3. Cmax of multiple oral doses [ Time Frame: Baseline through Day 14 ]
4. AUC0-t of multiple oral doses [ Time Frame: Baseline through Day 14 ]

Other Outcome Measures:

1. Change in nasal epithelial mRNA and protein expression over time [ Time Frame: Baseline through Day 21 ]
2. Change in sweat chloride over time [ Time Frame: Baseline through Day 21 ]
3. Change in FEV1 over time [ Time Frame: Baseline through Day 21 ]
4. Change in weight over time [ Time Frame: Baseline through Day 21 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of CF.
• Stable on Kalydeco dosing for both label indication and per label dosing for a minimum of 3 months at the time of randomization
• Forced expiratory volume in 1 second (FEV1) 40-90% predicted.
• Non-smoker and non-tobacco user for a minimum of 30 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 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.
• History of cancer within the past five years (excluding cervical CIS with curative therapy for at least one year prior to screening and non-melanoma skin cancer).
• History of organ transplantation.
• Any sinopulmonary infection or CF exacerbation requiring a change or addition of medication (including antibiotics) within 1 month of Study Day 1 or any other clinically significant infection as determined by the investigator within 1 month of Day 1.
• History of alcohol or drug abuse or dependence within 12 months of screening as determined by the Investigator.
• Male and female of child-bearing potential, unless they are using highly effective methods of contraception during participation in the clinical study and for 4 weeks after termination from study.
• Pregnant or nursing women.

Contacts and Locations

Locations

United Kingdom

Celerion

Belfast, United Kingdom, BT9 6AD

Medicines Evaluation Unit

Manchester, United Kingdom

Sponsors and Collaborators

Proteostasis Therapeutics, Inc.

More Information

• Responsible Party: Proteostasis Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03258424
• Other Study ID Numbers: PTI-428-05
• First Posted: August 23, 2017
• Last Update Posted: March 26, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases