Cystic Fibrosis
Conditions
Brief summary
The primary purpose of study is to evaluate the treatment effect of tezacaftor in combination with ivacaftor (TEZ/IVA) on chest imaging endpoints using low-dose computed tomography (LDCT) at Week 72, and to evaluate the safety of TEZ/IVA through Week 72.
Interventions
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
DRUGIvacaftor
IVA 150 mg tablet.
DRUGPlacebo
Placebo matched to TEZ/IVA fixed-dose combination tablet.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Homozygous for the F508del CFTR mutation * Confirmed diagnosis of CF * Percent predicted forced expiratory volume (ppFEV1) ≥70% of predicted normal for age, sex, and height during screening. * Stable CF disease as judged by the investigator
Exclusion criteria
* History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug) * Pregnant or nursing females. * Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. * Any contraindication to undergoing chest imaging, as per the site's institutional guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Total Brody/CF-CT Score | From Baseline at Week 72 | The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 76 |
Countries
Australia
Participant flow
Pre-assignment details
A total of 41 participants were randomized and treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| TEZ/IVA Participants received TEZ 100 mg/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks. | 20 |
| Placebo Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks. | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal of consent (not due to AE) | 0 | 1 |
Baseline characteristics
| Characteristic | Total | TEZ/IVA | Placebo |
|---|---|---|---|
| Age, Continuous | 20.2 years STANDARD_DEVIATION 8.4 | 20.4 years STANDARD_DEVIATION 7.5 | 20.1 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 20 Participants | 21 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 | 41 Participants | 20 Participants | 21 Participants |
| Sex: Female, Male Female | 21 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 20 Participants | 9 Participants | 11 Participants |
| Total Brody/Cystic Fibrosis - Computed Tomography (CF-CT) Score | 40.98 scores on a scale STANDARD_DEVIATION 28.72 | 38.29 scores on a scale STANDARD_DEVIATION 22.91 | 43.68 scores on a scale STANDARD_DEVIATION 33.96 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 21 |
| other Total, other adverse events | 19 / 20 | 20 / 21 |
| serious Total, serious adverse events | 8 / 20 | 13 / 21 |
Outcome results
Primary
Absolute Change in Total Brody/CF-CT Score
The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease.
Time frame: From Baseline at Week 72
Population: FAS included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TEZ/IVA | Absolute Change in Total Brody/CF-CT Score | 0.90 scores on a scale | Standard Error 2.09 |
| Placebo | Absolute Change in Total Brody/CF-CT Score | 2.38 scores on a scale | Standard Error 2.07 |
95% CI: [-7.47, 4.52]
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 76
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEZ/IVA | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 20 Participants |
| TEZ/IVA | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 8 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 21 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 13 Participants |