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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

Tracking Information
First Submitted Date  ICMJE August 7, 2018
First Posted Date  ICMJE August 9, 2018
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE December 1, 2018
Estimated Primary Completion Date November 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
lung function [ Time Frame: 24 weeks ]
change in Fev1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
Official Title  ICMJE Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE Drug: Tezacaftor/Ivacaftor
CFTR correctors
Study Arms  ICMJE 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.
Intervention: Drug: Tezacaftor/Ivacaftor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2021
Estimated Primary Completion Date November 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Heather Hathorne, PhD 205-638-9568
Contact: Ginger Reeves, BS 205-638-5970
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03624101
Other Study ID Numbers  ICMJE IRB-300001363
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Steven M Rowe, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Alabama at Birmingham
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP