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

Primary Purpose

Cystic Fibrosis

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Trikafta

symdeko/Trikafta

Ivacaftor/Trikafta

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Alabama at BirminghamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Trikafta

Symdeko/Trikafta

Ivacaftor/Trikafta

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

lung function

change in Fev1

Secondary Outcome Measures

Full Information

NCT ID

NCT03624101

First Posted

August 7, 2018

Last Updated

December 12, 2022

Sponsor

University of Alabama at Birmingham

1. Study Identification

Unique Protocol Identification Number

NCT03624101

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2018 (Actual)

Primary Completion Date

December 1, 2023 (Anticipated)

Study Completion Date

January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Alabama at Birmingham

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

2 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Trikafta

Arm Type

Experimental

Arm Description

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

Arm Title

Symdeko/Trikafta

Arm Type

Experimental

Arm Description

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

Arm Title

Ivacaftor/Trikafta

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Trikafta

Intervention Description

CFTR modulator

Intervention Type

Drug

Intervention Name(s)

symdeko/Trikafta

Intervention Description

CFTR modulator

Intervention Type

Drug

Intervention Name(s)

Ivacaftor/Trikafta

Intervention Description

CFTR modulator

Primary Outcome Measure Information:

Title

lung function

Description

change in Fev1

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Heather Hathorne, PhD

Phone

205-638-9568

hhathorne@peds.uab.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Ginger Reeves, BS

Phone

205-638-5970

greeves@peds.uab.edu

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Heather R Hathorne, MAE, RRT

Phone

205-939-9568

hhathorne@peds.uab.edu

First Name & Middle Initial & Last Name & Degree

Steven M Rowe, MD, MpH

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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