Glomerulosclerosis, Focal Segmental
Conditions
Brief summary
This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-147 in participants with apolipoprotein L1 (APOL1)-mediated focal segmental glomerulosclerosis (FSGS).
Interventions
DRUGVX-147
Tablets for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * APOL1 genotype of G1/G1, G2/G2, or G1/G2 * FSGS diagnosed by kidney biopsy Key
Exclusion criteria
* Evidence of non-APOL1-mediated FSGS * Participants with known sickle cell disease * Solid organ or Bone marrow transplant Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in UPCR | From Baseline up to Week 13 |
Secondary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Baseline up to Week 17 |
| Maximum Observed Concentration (Cmax) of VX-147 | Pre-dose and at 0.25, 0.5, 1, 2, 4, and 12 hours post-dose on Day 1 and Week 5 |
| Observed Pre-dose Concentration (Ctrough) of VX-147 | Pre-dose on Day 8, 15, Week 3, 5, 9 and 13 |
| Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24hr) of VX-147 | Pre-dose and at 0.25, 0.5, 1, 2, 4, 12 and 24 hours Post-dose on Week 5 |
Countries
France, Puerto Rico, United Kingdom, United States
Participant flow
Recruitment details
This study was planned in 2 parts: Part A (Treatment Period), which consisted of 2 cohorts (i.e., cohort 1 and 2) and Part B (Optional Exploratory Off-treatment Follow-up Period). The primary and secondary efficacy analyses and safety analyses were planned for only Part A.
Pre-assignment details
This study was conducted on adult participants who had APOL1-mediated focal segmental glomerulosclerosis (FSGS).
Participants by arm
| Arm | Count |
|---|---|
| VX-147 All participants received VX-147 at a dosage of 15 mg qd for 2 weeks and VX-147 at a dosage of 45 mg qd for 11 weeks. Part A was enrolled in 2 cohorts: Cohort 1 and Cohort 2. Cohort 1 included participants with urine protein to creatinine ratio (UPCR) approximately ≥3 g/g (± 10%) and \<10 g/g and estimated glomerular filtration rate (eGFR) approximately ≥30 mL/min/1.73 m2 (± 10%). Cohort 2 included participants with UPCR approximately ≥0.8 g/g (± 10%) and \<2.7 g/g and eGFR approximately ≥30 mL/min/1.73 m2. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal of consent (not due to adverse event) | 1 |
Baseline characteristics
| Characteristic | VX-147 |
|---|---|
| Age, Continuous Cohort 1 | 45.0 years STANDARD_DEVIATION 10.5 |
| Age, Continuous Cohort 2 | 37.3 years STANDARD_DEVIATION 15.2 |
| Ethnicity (NIH/OMB) Cohort 1 Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 1 Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Cohort 1 Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Cohort 1 American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Cohort 1 Asian | 0 Participants |
| Race (NIH/OMB) Cohort 1 Black or African American | 3 Participants |
| Race (NIH/OMB) Cohort 1 More than one race | 0 Participants |
| Race (NIH/OMB) Cohort 1 Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Cohort 1 Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Cohort 1 White | 0 Participants |
| Race (NIH/OMB) Cohort 2 American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Cohort 2 Asian | 0 Participants |
| Race (NIH/OMB) Cohort 2 Black or African American | 13 Participants |
| Race (NIH/OMB) Cohort 2 More than one race | 0 Participants |
| Race (NIH/OMB) Cohort 2 Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Cohort 2 Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Cohort 2 White | 0 Participants |
| Sex: Female, Male Cohort 1 Female | 2 Participants |
| Sex: Female, Male Cohort 1 Male | 1 Participants |
| Sex: Female, Male Cohort 2 Female | 7 Participants |
| Sex: Female, Male Cohort 2 Male | 6 Participants |
| Urine Protein to Creatinine Ratio (UPCR) Cohort 1 | 3.47 g/g STANDARD_DEVIATION 1.07 |
| Urine Protein to Creatinine Ratio (UPCR) Cohort 2 | 1.77 g/g STANDARD_DEVIATION 0.49 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 13 | 0 / 16 |
| other Total, other adverse events | 3 / 3 | 12 / 13 | 15 / 16 |
| serious Total, serious adverse events | 0 / 3 | 1 / 13 | 1 / 16 |
Outcome results
Primary
Percent Change From Baseline in UPCR
Time frame: From Baseline up to Week 13
Population: The Full Analysis Set (FAS) included all participants who received at least 1 dose of study drug in the treatment period. Here Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome and the Number Analyzed signifies participants who were evaluable for the specified Cohorts.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VX-147 | Percent Change From Baseline in UPCR | Cohort 1 | -47.7 percent change |
| VX-147 | Percent Change From Baseline in UPCR | Cohort 2 | -47.5 percent change |
| VX-147 | Percent Change From Baseline in UPCR | Total | -47.6 percent change |
Secondary
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24hr) of VX-147
Time frame: Pre-dose and at 0.25, 0.5, 1, 2, 4, 12 and 24 hours Post-dose on Week 5
Population: The PK set included all those who received at least 1 dose of study drug. Though participants in this study were divided into two cohorts based on their UPCR range, PK data was collected and presented based on dose levels as all participants received 15 mg qd for 2 weeks and 45 mg qd for 11 weeks. Therefore, presenting data based on cohorts as per UPCR range was not relevant for purpose of PK endpoints. Here Number Analyzed signifies participants who were evaluable at specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VX-147 | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24hr) of VX-147 | 15.3 hour*mcg/mL (h*mcg/mL) | Standard Deviation 6.37 |
Secondary
Maximum Observed Concentration (Cmax) of VX-147
Time frame: Pre-dose and at 0.25, 0.5, 1, 2, 4, and 12 hours post-dose on Day 1 and Week 5
Population: The PK set included all those who received at least 1 dose of study drug. Though participants in this study were divided into two cohorts based on their UPCR range, PK data was collected and presented based on dose levels as all participants received 15 mg qd for 2 weeks and 45 mg qd for 11 weeks. Therefore, presenting data based on cohorts as per UPCR range was not relevant for purpose of PK endpoints. Here Number Analyzed signifies participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-147 | Maximum Observed Concentration (Cmax) of VX-147 | 15 mg qd: Day 1 | 0.168 micrograms per milliliter (mcg/ml) | Standard Deviation 0.063 |
| VX-147 | Maximum Observed Concentration (Cmax) of VX-147 | 45 mg qd: Week 5 | 0.846 micrograms per milliliter (mcg/ml) | Standard Deviation 0.303 |
Secondary
Observed Pre-dose Concentration (Ctrough) of VX-147
Time frame: Pre-dose on Day 8, 15, Week 3, 5, 9 and 13
Population: The PK set included all those who received at least 1 dose of study drug. Though participants in this study were divided into two cohorts based on their UPCR range, PK data was collected and presented based on dose levels as all participants received 15 mg qd for 2 weeks and 45 mg qd for 11 weeks. Therefore, presenting data based on cohorts as per UPCR range was not relevant for purpose of PK endpoints. Here Number Analyzed signifies participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 15 mg qd: Day 8 | 0.153 mcg/ml | Standard Deviation 0.0984 |
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 15 mg qd: Day 15 | 0.123 mcg/ml | Standard Deviation 0.0796 |
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 45 mg qd: Week 3 | 0.379 mcg/ml | Standard Deviation 0.249 |
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 45 mg qd: Week 5 | 0.492 mcg/ml | Standard Deviation 0.265 |
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 45 mg qd: Week 9 | 0.446 mcg/ml | Standard Deviation 0.342 |
| VX-147 | Observed Pre-dose Concentration (Ctrough) of VX-147 | 45 mg qd: Week 13 | 0.529 mcg/ml | Standard Deviation 0.302 |
Secondary
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Baseline up to Week 17
Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period. Here, the Number Analyzed signifies participants who were evaluable for the specified cohorts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VX-147 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Cohort 1: Participants With TEAEs | 3 Participants |
| VX-147 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Cohort 1: Participants With SAEs | 0 Participants |
| VX-147 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Cohort 2: Participants With TEAEs | 12 Participants |
| VX-147 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Cohort 2: Participants With SAEs | 1 Participants |