Cystic Fibrosis
Conditions
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.
Interventions
DRUGSymdeko
CFTR modulator
DRUGIvacaftor and Symdeko
CFTR modulator
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in FEV1 From Baseline | 24 weeks | Percent change in FEV1 from Baseline and 24 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Symdeko If the participant is on symdeko, they will take symdeko for 28 days followed by a 28 day off period. This cycle will be continued for 168 day
Symdeko: CFTR modulator | 1 |
| Symdeko/Ivacaftor If the participant currently takes Symdeko , they will take Symdeko for a 28 day period followed by Ivacaftor for a 28 day period. This cycle will be continued for 168 days
symdeko/Ivacaftor: CFTR modulator | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Symdeko | Total | Symdeko/Ivacaftor |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | — |
| Age, Continuous | 37 years | 37 years | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | — |
| Sex: Female, Male Female | 0 Participants | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Percent Change in FEV1 From Baseline
Percent change in FEV1 from Baseline and 24 weeks
Time frame: 24 weeks
Population: no improvement was noticed and the study ended prematurely. No formal statistical analysis was performed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symdeko | Percent Change in FEV1 From Baseline | 0 change in percentage |