Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations

• ClinicalTrials.gov Identifier: NCT03256799
• Recruitment Status: Completed
• First Posted: August 22, 2017
• Results First Posted: July 19, 2019
• Last Update Posted: July 19, 2019
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Steven M Rowe, University of Alabama at Birmingham

Study Description

Brief Summary:

The purpose of this study is to explore the combination of Ataluren and ivacaftor as a treatment for patients with a specific cystic fibrosis mutation

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Ivacaftor/Ataluren	Phase 4

Detailed Description:

In about 10% of patients with CF, the defect in the gene is known as a stop mutation. This mutation truncates the cystic fibrosis transductive regulator (CFTR) protein production by introducing a premature stop in the messenger RNA (mRNA), this type of mutation is known as a stop mutation. Ataluren is a novel, oral drug that promotes this gene to work effectively and readthrough that premature "stop sign". It is hypothesized that ivacaftor may increase the efficacy of Ataluren by activating a specific protein that may not be functioning properly.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study to Investigate the Role of Ivacaftor for the Treatment of Cystic Fibrosis in Combination With Ataluren (PTC124) in Cystic Fibrosis Patients Using Ataluren for Nonsense Mutations
• Actual Study Start Date: March 17, 2017
• Actual Primary Completion Date: July 10, 2017
• Actual Study Completion Date: February 16, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ivacaftor/Ataluren	Drug: Ivacaftor/Ataluren; Both drugs were given in combination for 48 week study period

Outcome Measures

Primary Outcome Measures :

1. Lung Function [ Time Frame: Baseline through 48 weeks ]
   change in lung function as measured by spirometry

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial.
2. Age ≥19 years
3. Body weight ≥16 kg
4. Diagnosis of cystic fibrosis and documentation of the presence of a nonsense mutations of the CFTR gene, as determined by historical genotyping
5. Ability to perform a valid, reproducible spirometry with demonstration of a forced expiratory volume in 1second (FEV1) ≥30% of predicted for age, gender, and height.
6. If the subject is sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration
7. Willingness and ability to comply with all study procedures and assessments.
8. Currently receiving Ataluren for nonsense mutations through other clinical trial access.

Exclusion Criteria:

1. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 2 weeks prior to screening.
2. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 2 weeks prior to screening.
3. Ongoing immunosuppressive therapy (other than corticosteroids up to 10mg/d equivalent of prednisone)
4. Ongoing warfarin, phenytoin, or tolbutamide therapy.
5. History of solid organ or hematological transplantation.
6. A history of positive hepatitis B surface antigen test, hepatitis C antibody test, or human immunodeficiency
7. Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 4 weeks prior to screening.
8. Pregnancy or breast-feeding.
9. Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day × number of years smoked).

10. Prior or ongoing medical condition (eg, renal failure, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

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Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

• Principal Investigator: Steven M Rowe, MD; University of Alabama at Birmingham

  Study Documents (Full-Text)

Documents provided by Steven M Rowe, University of Alabama at Birmingham:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] February 1, 2019

More Information

• Responsible Party: Steven M Rowe, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03256799
• Other Study ID Numbers: F161208009
• First Posted: August 22, 2017
• Results First Posted: July 19, 2019
• Last Update Posted: July 19, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: 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; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action