Alport Syndrome, Autosomal Dominant Polycystic Kidney, Chronic Kidney Diseases
Conditions
Keywords
Bardoxolone methyl, CDDO-ME, RTA 402, Alport Syndrome, Autosomal Dominant Polycystic Kidney, ADPKD
Brief summary
This extended access study will assess the long-term safety and tolerability of bardoxolone methyl in qualified patients with chronic kidney disease (CKD) who previously participated in one of the qualifying clinical studies with bardoxolone methyl. Patients will remain in the study until bardoxolone methyl is available through commercial channels or until patient withdrawal, whichever is sooner.
Interventions
Bardoxolone methyl capsules
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are participating (or who have participated) in qualifying studies and who have not been required to discontinue study treatment for protocol or safety reasons and who have completed required End-of-Treatment and/or Follow-up visits in a prior clinical study with bardoxolone methyl and who, according to the assessment of the investigator, have a potential positive benefit-risk assessment for participating in the trial. * Meets the following eligibility criteria based on assessments from the prior qualifying study (last on-treatment visit) or from a screening visit, if applicable: 1. Not expected to reach end stage kidney disease (ESKD) or nephrotic syndrome within 12 weeks of study enrollment, in the investigator's judgement; subjects with eGFR \<20 ml/min/1.73m2 should be discussed with the medical monitor before enrollment (e.g., such subjects with an average rate of eGFR decline \> 1.0 ml/min/1.73m2 per month in the 3 months prior to eligibility assessment may not be eligible); 2. BNP \< 200 pg/mL at the last on-treatment visit in the prior qualifying study or at a new screening visit, if applicable; 3. No occurrence of a cardiovascular serious adverse event in the prior qualifying study or in the interval between the end of the qualifying study and the screening visit, if applicable. * Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Evidence of a personally signed and dated informed consent document (and assent form if necessary) indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any protocol-mandated procedures.
Exclusion criteria
* Participation in other investigational clinical studies involving interventional products being tested or used in a way different from the approved form or when used for an unapproved indication; * Patients who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bardoxolone methyl; * Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) while screening, taking study drug and 30 days after the last study drug dose; * Women who are pregnant or breastfeeding; * Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason; * Known hypersensitivity to any component of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. AEs and SAEs that occurred within 30 days after the last dose were considered treatment-emergent. The study follow-up assessment was collected within 14 to 35 days after the last dose. |
Countries
Australia, France, Japan, Puerto Rico, Spain, United States
Participant flow
Recruitment details
Participants were enrolled at the investigative sites in the United States, Australia, Japan, Spain, Puerto Rico and France from 08 March 2019 to 23 August 2023.
Pre-assignment details
A total of 270 eligible participants who participated in the previous qualifying studies i.e., 402-C-1603 (NCT03019185) and 402-C-1808 (NCT03918447) of bardoxolone methyl were enrolled in this study. Data was summarized as per the treatment received in the previous qualifying studies.
Participants by arm
| Arm | Count |
|---|---|
| Prior Placebo to Bardoxolone Methyl Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study.
Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study.
Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study. | 143 |
| Prior Bardoxolone Methyl to Bardoxolone Methyl Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study.
Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study.
Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study. | 127 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Non-compliance With Study Drug | 0 | 1 |
| Overall Study | Physician Decision | 4 | 3 |
| Overall Study | Protocol-Specified Withdrawal Criteria Met | 1 | 3 |
| Overall Study | Reason Not Specified | 0 | 3 |
| Overall Study | Study Terminated By Sponsor | 112 | 105 |
| Overall Study | Withdrawal by Subject | 12 | 6 |
Baseline characteristics
| Characteristic | Prior Bardoxolone Methyl to Bardoxolone Methyl | Total | Prior Placebo to Bardoxolone Methyl |
|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 13.82 | 48.6 years STANDARD_DEVIATION 13.5 | 48.8 years STANDARD_DEVIATION 13.26 |
| Race/Ethnicity, Customized Ethnicity Hispanic/Latino | 12 Participants | 27 Participants | 15 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic/Latino | 115 Participants | 243 Participants | 128 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 16 Participants | 33 Participants | 17 Participants |
| Race/Ethnicity, Customized Race Black or African American | 9 Participants | 18 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 96 Participants | 208 Participants | 112 Participants |
| Sex: Female, Male Female | 78 Participants | 166 Participants | 88 Participants |
| Sex: Female, Male Male | 49 Participants | 104 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 143 | 1 / 127 |
| other Total, other adverse events | 127 / 143 | 104 / 127 |
| serious Total, serious adverse events | 12 / 143 | 20 / 127 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. AEs and SAEs that occurred within 30 days after the last dose were considered treatment-emergent. The study follow-up assessment was collected within 14 to 35 days after the last dose.
Time frame: From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years)
Population: The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Placebo to Bardoxolone Methyl | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 128 Participants |
| Prior Placebo to Bardoxolone Methyl | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 12 Participants |
| Prior Bardoxolone Methyl to Bardoxolone Methyl | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 105 Participants |
| Prior Bardoxolone Methyl to Bardoxolone Methyl | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 20 Participants |