A Trial of Bardoxolone Methyl in Patients With ADPKD – FALCON

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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 Phase

Phase 3

Study Type

Interventional


Primary Outcome

Change in eGFR from baseline (52 weeks)

Secondary Outcome

 Change in eGFR from baseline (104 weeks)

Condition

Autosomal Dominant Polycystic Kidney

Intervention

Bardoxolone methyl oral capsule

Study Arms / Comparison Groups

 Maximum bardoxolone methyl dose of 20 mg
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

550

Start Date

May 29, 2019

Completion Date

December 2023

Primary Completion Date

December 2023

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
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

, +1 469-442-4754, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT03918447

Organization ID

402-C-1808


Responsible Party

Sponsor

Study Sponsor

Reata Pharmaceuticals, Inc.


Study Sponsor

, , 


Verification Date

October 2021