Glycerol Phenylbutyrate Corrector Therapy For CF (Cystic Fibrosis)

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

We propose to test the effectiveness of the combination of CF pancreatic enzyme replacement therapy (PERT) on absorption of Ravicti® and subsequent restoration of nasal epithelial cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport during the nasal potential difference (NPD) test. Funding source FDA Office of Orphan Products Development.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University; National Jewish Health
• Collaborators: Children's Hospital of Philadelphia; Horizon Pharma Ireland, Ltd., Dublin Ireland; Johns Hopkins University; University of Alabama at Birmingham
• Treatments: 4-phenylbutyric acid; Glycerol

Criteria

Inclusion Criteria:

1. Male or female ≥ 18 years of age.

2. Confirmed diagnosis of CF based on the following criteria:

any CFTR genotype combination EXCEPT two stop codons, and one or more clinical features consistent with the CF phenotype.

3. Taking pancreatic enzyme replacement therapy (PERT), or have documented pancreatic sufficiency.

4. Ability to perform acceptable spirometry.

5. Ability to understand and sign a written informed consent and comply with the requirements of the study.

6. FEV1 ≥30% of predicted normal for age, gender, and height (Hankinson standards): pre or post-bronchodilator at Screening.

7. Oxygen saturation by pulse oximetry ≥90% breathing either ambient air or regular oxygen regimen at screening and Day 1.

8. Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments (as judged by the principal investigator) at screening. If electrolyte abnormality at screening, values must be corrected prior to dosing.

9. Subjects on chronic inhaled antibiotic therapy are eligible if they can continue their usual antibiotic regimen, or remain on their off-cycle period, for the duration of study drug exposure

10. Negative pregnancy test for women of child-bearing potential.

11. If of childbearing potential, agree to use one highly effective method of contraception from the time of consent through the Visit 4 study visit, per section 9.1.13 of the protocol.

Exclusion Criteria:

1. Administration of any investigational drug or device within 30 days of Screening or within 6 half-lives of the investigational drug (whichever is longer).

2. History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk in administering study drug to subjects.

3. Any change in chronic therapies for CF lung disease (e.g., Ibuprofen, Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1.

4. Pregnant, planned pregnancy or breast feeding at Screening.

5. Clinically significant cardiac, liver or kidney disease.

6. Seizure disorder.

7. Acute upper respiratory infection within 2 weeks or acute pulmonary exacerbation requiring intravenous antibiotics within 4 weeks of Screening Visit.

8. Sinus surgery within 6 weeks of Screening Visit.

9. Abnormal renal function.

10. Abnormal liver function, defined as ≥3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis.

11. Screening laboratory results which in the judgment of the investigator would interfere with completion of the study.

12. History of or listed for solid organ or hematological transplantation.