Cystic FibrosisPhase 4NCT03624101
Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
A Phase 4 study testing Symdeko and Ivacaftor and Symdeko in people with Cystic Fibrosis, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Symdeko and Ivacaftor and Symdeko
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2018to 3 Oct 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35233
About this study
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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Symdeko, Ivacaftor and Symdeko
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SymdekoDrug
CFTR modulator
Ivacaftor and SymdekoDrug
CFTR modulator
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Ivacaftor and Symdeko |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in FEV1 From Baseline
Percent change in FEV1 from Baseline and 24 weeks
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start1 Dec 2018
- Primary completion3 Oct 2019
- Study completion3 Oct 2019
Why it stopped: summary results revealed ineffective intervention and the trial was terminated prematurely. No formal statistical analysis was performed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven M Rowe, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03624101
- Sponsor's protocol ID
- IRB-300001363
- Status last verified
- Apr 2025
- First submitted
- 7 Aug 2018
- Last updated
- 16 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
- ClinicalTrials.gov ID
- NCT03624101
- Acronym / sponsor ID
- IRB-300001363
- Conditions
- Cystic Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: summary results revealed ineffective intervention and the trial was terminated prematurely. No formal statistical analysis was performed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 3 Oct 2019 (actual)
- Study completion
- 3 Oct 2019 (actual)
- First posted
- 9 Aug 2018 (actual)
- Results
- Posted 16 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Symdeko | Experimental | Drug: SymdekoIf 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 |
| Symdeko/Trikafta | Experimental | Drug: Ivacaftor and SymdekoIf 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SymdekoCFTR modulator | Drug | Symdeko |
| Ivacaftor and SymdekoCFTR modulator | Drug | Symdeko/Trikafta |
Primary outcome
Percent Change in FEV1 From Baseline
Time frame: 24 weeks
Percent change in FEV1 from Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Symdeko and Ivacaftor and Symdeko in people with Cystic Fibrosis, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in FEV1 From Baseline (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.