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Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03624101
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : May 29, 2020
Information provided by (Responsible Party):
Steven M Rowe, University of Alabama at Birmingham

Brief Summary:
Based on previous clinical findings, the investigator hypothesize that ivacaftor will have synergistic effects with drugs that facilitate truncated but partially active W1282X CFTR protein processing (tezacaftor) in patients with W1282X CFTR. In the current study, the investigators propose to directly test the efficacy of tezacaftor/ivacaftor (TEZ/IVA) for W1282X CFTR therapy in the clinic in comparison to ivacaftor alone.

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

Detailed Description:
Approximately 11% of CF patients have premature termination codons (PTC), causing truncated CFTR with little to no function. No approved therapies exist for patients with PTC mutations including W1282X, a unique mutation exhibiting partial CFTR activity even in its truncated form. CFTR modulators alone enhanced CFTR function in patient cells from W1282X/G542X CFTR. Several published studies have shown CFTR modulators alone and/or in combination with readthrough (RT) agents benefit W1282X CFTR. Clinical studies further support an aspect of this notion, where two W1282X patients showed beneficial effect to Ivacaftor treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ivacaftor

Arm Intervention/treatment
Experimental: tezacaftor/ivacaftor
After a 4-week screening period to confirm eligibility based on study inclusion and exclusion criteria subjects will receive Symdeko in 3 intermittent four-week intervals, followed by a 4-week follow-up period (for safety and to detect efficacy changes upon washout) Symdeko (Ivacaftor (150 mg daily) Tezacaftor (100 mg daily) will be administered at the approved dose in combination pill, and alternated with ivacaftor.
Drug: Tezacaftor/Ivacaftor
CFTR correctors

Primary Outcome Measures :
  1. lung function [ Time Frame: 24 weeks ]
    change in Fev1

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • 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

    • Age ≥ 18 yrs
    • Body weight ≥ 16 kg
    • Diagnosis of CF and documentation of the presence of a nonsense mutation of the CFTR gene, as determined by historical genotyping
    • Ability to perform a valid, reproducible spirometry with demonstration of FEV1 ≥ 30% and ≤ 90% of predicted for age, gender, and height
    • In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration
    • Willingness and ability to comply with all study procedures and assessments

Exclusion Criteria:

  • 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
  • Ongoing participation in any other therapeutic clinical trial
  • Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 2 weeks prior to screening
  • History of solid organ or hematological transplantation; positive hepatitis B surface antigen test; hepatitis C antibody test; or human immunodecifiency
  • Major complication of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 4 weeks prior to screening
  • Pregnancy or breast-feeding
  • Current smoker or a smoking history of ≥ 10 pack-years (number of cigarette packs/day x number of years smoked)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03624101

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Contact: Heather Hathorne, PhD 205-638-9568
Contact: Ginger Reeves, BS 205-638-5970

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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Heather R Hathorne, MAE, RRT    205-939-9568   
Principal Investigator: Steven M Rowe, MD, MpH         
Sponsors and Collaborators
University of Alabama at Birmingham
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Responsible Party: Steven M Rowe, Principal Investigator, University of Alabama at Birmingham Identifier: NCT03624101    
Other Study ID Numbers: IRB-300001363
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Cystic Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action