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

NCT03624101 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: IRB-300001363
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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) and Trikafta for W1282X CFTR therapy in the clinic in comparison to ivacaftor alone.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Percent Change in FEV1 From Baseline

  Percent change in FEV1 from Baseline and 24 weeks

  24 weeks

Study Arms (2)

Symdeko

EXPERIMENTAL

If the participant is not on a current modulator, they will take Symdeko for 28 days followed by a 28 day off period. This cycle will be continued for 168 days

Drug: Symdeko

Symdeko/Trikafta

EXPERIMENTAL

If the participant currently takes Symdeko , they will take Trikafta for a 28 day period followed by Symdeko for a 28 day period. This cycle will be continued for 168 days

Drug: Ivacaftor and Symdeko

Interventions

Symdeko DRUG

CFTR modulator

Symdeko

Ivacaftor and Symdeko DRUG

CFTR modulator

Symdeko/Trikafta

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

tezacaftor, ivacaftor drug combination; ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

the data collected was not compelling enough to move forward and no publications or official findings were available

Results Point of Contact

• Title: Heather Hathorne
• Organization: University of Alabama at Birmingham Child Health Research Unit

hyhathorne@uabmc.edu

2055032829

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 9, 2018
• Study Start: December 1, 2018
• Primary Completion: October 3, 2019
• Study Completion: October 3, 2019
• Last Updated: April 16, 2025
• Results First Posted: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)