Efficacy and Safety Study to Evaluate Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE)

• ClinicalTrials.gov Identifier: NCT02865850
• Recruitment Status: Active, not recruiting
• First Posted: August 15, 2016
• Last Update Posted: October 11, 2019
• Sponsor: Akebia Therapeutics
• Information provided by (Responsible Party): Akebia Therapeutics

Study Description

Brief Summary:

A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction or maintenance treatment of anemia in subjects with incident DD-CKD.

Condition or disease	Intervention/treatment	Phase
Anemia; Dialysis-dependent Chronic Kidney Disease	Drug: vadadustat; Drug: Darbepoetin alfa	Phase 3

Detailed Description:

This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of vadadustat versus darbepoetin alfa for the correction or maintenance treatment in subjects with anemia secondary to CKD who have recently initiated dialysis treatment for end-stage renal disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 369 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - CORRECTION/CONVERSION)
• Actual Study Start Date: July 2016
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: May 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vadadustat	Drug: vadadustat; oral tablet; Other Name: AKB-6548
Active Comparator: darbepoetin alfa	Drug: Darbepoetin alfa; subcutaneous/intravenous; Other Name: aranesp

Outcome Measures

Primary Outcome Measures :

1. Mean change in Hb between baseline and the primary evaluation period [ Time Frame: Baseline visit, Week 36 ]
2. Major adverse cardiovascular events (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke [ Time Frame: From baseline visit to end of study (event-driven, minimum 1 year) ]

Secondary Outcome Measures :

1. Mean change in Hb value between Baseline and the secondary evaluation period [ Time Frame: Baseline visit, Week 52 ]
2. Proportion of subjects with Hb values within the target range during the primary evaluation period [ Time Frame: Baseline visit, Week 36 ]
3. AEs and SAEs [ Time Frame: Baseline visit to end of study (event-driven, minimum 1 year) ]
4. Proportion of time with Hb values within the target range during the primary evaluation period [ Time Frame: Baseline visit, Week 36 ]
5. Proportion of time with Hb values within the target range during the secondary evaluation period [ Time Frame: Baseline visit, Week 52 ]
6. Proportion of subjects with Hb values within the target range during the secondary evaluation period [ Time Frame: Baseline visit, Week 52 ]
7. Proportion of subjects with Hb increase of >1.0 g/dL from Baseline visit [ Time Frame: From baseline visit to end of study (event-driven, minimum 36 weeks) ]
8. Time to achieve Hb increase of >1.0 g/dL from Baseline visit [ Time Frame: From baseline visit to end of study (event-driven, minimum 36 weeks) ]
9. Mean change in Hb between Baseline (mean pretreatment Hb) and the primary evaluation period (mean Hgb from Week s24-36 stratified by pre-baseline ESA exposure [ Time Frame: Baseline visit, Week 36 ]
10. Proportion of subjects receiving IV iron therapy [ Time Frame: Baseline visit, Week 52 ]
11. Mean monthly dose of IV elemental iron administered in subjects who have received IV iron [ Time Frame: Baseline visit, Week 52 ]
12. Proportion of subjects receiving RBC transfusion(s) [ Time Frame: Baseline visit, Week 52 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ≥18 years of age
• Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
• Mean Screening hemoglobin between 8.0 and <11.0 g/dL (inclusive)

Exclusion Criteria:

• Subjects meeting the criteria of ESA resistance within 8 weeks prior to or during Screening defined as follows

  1. epoetin: > 7700 units/dose three times per week or >23,000 units per week
  2. darbepoetin alfa: >100 mcg/week
  3. methoxy polyethylene glycol-epoetin beta: >100 mcg every other week or >200 mcg/month
• Anemia due to a cause other than CKD or subjects with active bleeding or recent blood loss
• Anticipated to recover adequate kidney function to no longer require dialysis
• Uncontrolled hypertension
• Severe heart failure at Screening (New York Heart Association Class IV)
• Acute coronary syndrome (hospitalization for unstable angina, myocardial infarction); surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity); surgical or percutaneous valvular replacement or repair; sustained ventricular tachycardia; hospitalization for CHF; or stroke within 12 weeks prior to or during Screening.
• Hypersensitivity to vadadustat, darbepoetin alfa or any of their excipients

Contacts and Locations

  Show 118 Study Locations

Sponsors and Collaborators

Akebia Therapeutics

Investigators

• Study Director: Akebia Therapeutics; Sponsor GmbH

More Information

• Responsible Party: Akebia Therapeutics
• ClinicalTrials.gov Identifier: NCT02865850 History of Changes
• Other Study ID Numbers: AKB-6548-CI-0016; 2016-000838-21 ( EudraCT Number )
• First Posted: August 15, 2016
• Last Update Posted: October 11, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Akebia Therapeutics:

vadadustat; AKB-6548; anemia; chronic kidney disease; CKD; chronic renal insufficiency; renal impairment; erythropoietin; kidney; renal; oral anemia treatment; hemoglobin; hypoxia-inducible factor; HIF; efficacy; safety; phase 3; cardiovascular

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematologic Diseases; Urologic Diseases; Renal Insufficiency; Darbepoetin alfa; Glycine; Hematinics; Glycine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs