A Multi-center, Randomized, Placebo-Controlled Phase I/II Study Designed to Assess the Safety, Tolerability, and how the body breaks down the drug PTI-428 in Subjects with Cystic Fibrosis

Phase 1

• Conditions: Cystic Fibrosis; MedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2016-001214-24-DE
• Lead Sponsor: Proteostasis Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-04-10
• Last Update Posted: 30 March 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

General study inclusion criteria:
1. Adult males or females age 18 years and older
2. Confirmed diagnosis of CF, defined as:
- A sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis and Clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities.
(OR)
- 2 CF-causing mutations (all as documented in the subject’s medical record) and Clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities.
3. FEV1 between 40-90% predicted
4. Pulse Oximetry > 92% at rest
5. Body mass index (BMI) =17 kg/m2
6. Subjects of child-bearing potential and who are sexually active must meet the study contraception requirements.
7. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study.
8. Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures and provides informed consent/permission prior to any study procedures being performed.

Stable ORKAMBI® Combination Cohort
- Stable on ORKAMBI® dosing for both label indication and per label dosing for a
minimum of three months at the time of randomization

ORKAMBI® Naïve Combination Cohort
- Eligible to take ORKAMBI® in accordance with the label.

Stable KALYDECO® Combination Cohort
- Stable on KALYDECO® dosing for both label indication and per label dosing for a minimum of three months at the time of randomization.

PTI-428 Monotherapy Cohort
- Pancreatic sufficiency as defined by lack of need for digestive enzymatic supplementation for at least 3 months and historical (within past year) or screening fecal elastase = 200 mcg/g stool.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. History or current evidence of any clinically significant cardiac, endocrinologic,
hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary (besides
CF), neurologic, dermatologic, psychiatric, renal, or other major disease, as determined
by the Investigator.
2. History of prolonged QT/QTc interval with Fridericia’s correction QTcF > 450 msec
at screening.
3. Abnormal liver function as defined by:
a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin
> 3 x upper limit of the normal range.
4. Abnormal renal function at screening defined as:
a. Creatinine clearance < 60mL/min using the Cockroft-Gault equation.
5. White Blood Cell Count (WBC) < 4,000 cells/mm3.
6. Clinically significant screening results that would exclude subject from the study (e.g., medical histories, physical examination, ECGs, vital signs, pulse oximetry, laboratoryprofiles) as deemed by the investigator.
7. Platelet count < 150,000 cell/mm3.
8. Recent hospitalization or change in CF medication (excluding pancreatic enzymes) within 1 month of Study Day 1.
9. 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.
10. Participant is currently taking or has taken KALYDECO® or ORKAMBI® within 14 days prior to initial dose of PTI-428 or placebo (unless participating in the Kalydeco / Orkambi stable cohort)
11. Subjects with a body weight > 120 kg at screening.
12. 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).
13. History of organ transplantation.
14. History of alcohol or drug abuse or dependence within 12 months of screening as determined by the Investigator.
15. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine cotinine is the detection mechanism for nicotine], opiates, barbiturates, amphetamines, and benzodiazepines) or positive alcohol testing at screening.
16. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb) at screening.
17.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.
18. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof.
19. Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion.
20. Pregnant or nursing women.
21. Any conditions that, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject’s participation in or completion of the study.
21.Institutionalised because of a legal or regulatory order.
22.Subjects who are employees of the sponsor.
23.Relatives of, or staff directly reporting to, the Investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified