A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON (FALCON)

• ClinicalTrials.gov Identifier: NCT03918447
• Recruitment Status: Recruiting
• First Posted: April 17, 2019
• Last Update Posted: February 2, 2021
• Sponsor: Reata Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Reata Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: April 12, 2019
• First Posted Date: April 17, 2019
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: May 29, 2019
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 21, 2020)

• Change in eGFR from baseline (52 weeks) [ Time Frame: 52 weeks ]
  To assess the off-treatment change from baseline in estimated glomerular filtration rate (eGFR) at Week 52 or following a 4-week drug treatment withdrawal period in the first year of treatment, for patients receiving active drug, compared to patients receiving placebo.
• Count of reported adverse events [ Time Frame: 104 weeks ]
  Safety and tolerability will be assessed by counting adverse events, as defined by the Medical Dictionary for Regulatory Activities (MedDRA)

Original Primary Outcome Measures (submitted: April 16, 2019)

• Change in eGFR from baseline (52 weeks) [ Time Frame: 52 weeks ]
  To assess the change in eGFR value from baseline to week 52, including a 4-week drug treatment withdrawal period, for patients receiving active drug, compared to patients receiving placebo.
• Count of reported adverse events [ Time Frame: 104 weeks ]
  Safety and tolerability will be assessed by counting adverse events, as defined by the Medical Dictionary for Regulatory Activities (MedDRA)

Current Secondary Outcome Measures (submitted: August 21, 2020)

Change in eGFR from baseline (104 weeks) [ Time Frame: 104 weeks ]

To assess the off-treatment change from baseline in eGFR at Week 104 or following a 4-week drug treatment withdrawal period in the second year of treatment., for patients receiving active drug, compared to patients receiving placebo.

Original Secondary Outcome Measures (submitted: April 16, 2019)

Change in eGFR from baseline (104 weeks) [ Time Frame: 104 weeks ]

To assess the change in eGFR value from baseline to week 104, including a 4-week drug treatment withdrawal period, for patients receiving active drug, compared to patients receiving placebo.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
• Official Title: A Phase 3 Trial of Bardoxolone Methyl in Patients With Autosomal Dominant Polycystic Kidney Disease
• Brief Summary: This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD. Approximately 300 patients will be enrolled.

Detailed Description

This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD.

Patients will be randomized 1:1 to either bardoxolone methyl or placebo. Patients receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Dose de-escalation is permitted during the study if indicated clinically, and subsequent dose re-escalation is also permitted to meet the dosing objective of the highest tolerated dose.

All patients in the study will follow the same visit and assessment schedule. Following randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 and by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they received at Week 48 and will continue study drug treatment through Week 100. Patients will also be scheduled to be assessed at an in-person follow-up visit at Week 104, four weeks after the end of treatment.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Autosomal Dominant Polycystic Kidney
• ADPKD

Intervention

• Drug: Bardoxolone methyl oral capsule
  Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.
  Other Name: RTA 402
• Drug: Placebo oral capsule
  Capsule containing an inert placebo

Study Arms

• Experimental: Maximum bardoxolone methyl dose of 20 mg

  Patients randomized to receive bardoxolone methyl with a baseline ACR less than or equal to 300 mg/g will be titrated to a maximum dose of 20 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2 and 20 mg at Week 4.

  Patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they received at Week 48 and will continue study drug treatment through Week 100.

  Patients will be assessed at an in-person follow-up visit at Week 104.

  Intervention: Drug: Bardoxolone methyl oral capsule
• Experimental: Maximum bardoxolone methyl dose 30 mg

  Patients randomized to receive bardoxolone methyl with a baseline ACR greater than 300 mg/g will be titrated to a maximum dose of 30 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2, 20 mg at Week 4 and 30 mg at Week 6.

  Patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they received at Week 48 and will continue study drug treatment through Week 100.

  Patients will be assessed at an in-person follow-up visit at Week 104.

  Intervention: Drug: Bardoxolone methyl oral capsule
• Placebo Comparator: Placebo

  Patients randomized to placebo will remain on placebo capsules throughout the study, undergoing sham titration.

  Patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive placebo during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 and will continue treatment through Week 100.

  Patients will be assessed at an in-person follow-up visit at Week 104

  Intervention: Drug: Placebo oral capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 16, 2019): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2023
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients 18 ≤ age ≤ 70 upon study consent;
• Diagnosis of ADPKD by modified Pei-Ravine criteria: 1) at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or 2) at least 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history;

• Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 30 to≤ 90 mL/min/1.73 m2 (18 to 55 years) or ≥ 30 to ≤ 44 mL/min/1.73 m2 (56 to 70 years):

  1) Patients with either screening eGFR ≥ 60 to ≤ 90 mL/min/1.73 m2 or age 56 to 70 years, must have evidence of ADPKD progression (i.e., eGFR decline of ≥ 2.0 mL/min/1.73 m2 per year, based on historical eGFR data and medical monitor discretion); 2)The two eGFR values collected at Screen A and Screen B visits used to determine eligibility must have a percent difference ≤ 25%;

• Albumin to creatinine ratio (ACR) ≤ 2500 mg/g at Screen B visit;
• Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at Screen A visit after a period of rest.

Exclusion Criteria:

• History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screen A visit;
• B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
• Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
• Serum albumin < 3 g/dL at Screen A visit;
• History of intracranial aneurysms;
• Kidney or any other solid organ transplant recipient or a planned transplant during the study;
• Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
• History of clinically significant left-sided heart disease and/or clinically significant cardiac disease;
• Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
• BMI < 18.5 kg/m2 at the Screen A visit;
• History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
• Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
• Untreated or uncontrolled active bacterial, fungal, or viral infection;
• Participation in other interventional clinical studies within 30 days prior to Day 1;
• Unwilling to practice acceptable methods of birth control (both males who have partners of child-bearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;
• Women who are pregnant or breastfeeding;
• Concomitant use of tolvaptan is excluded. Patients previously treated with tolvaptan must have discontinued drug for at least 3 months prior to Screen A visit

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Manager; +1 469-442-4754; FALCON@reatapharma.com

• Listed Location Countries: Australia, Belgium, Czechia, France, Germany, Italy, Japan, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03918447
• Other Study ID Numbers: 402-C-1808
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Reata Pharmaceuticals, Inc.
• Study Sponsor: Reata Pharmaceuticals, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Reata Pharmaceuticals, Inc.
• Verification Date: January 2021