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)

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)

Sponsors

Lead Sponsor: Akebia Therapeutics

Source Akebia Therapeutics
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.

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.

Overall Status Completed
Start Date July 2016
Completion Date March 30, 2020
Primary Completion Date January 31, 2020
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean change in Hb between baseline and the primary evaluation period Baseline visit, Week 36
Major adverse cardiovascular events (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke From baseline visit to end of study (event-driven, minimum 1 year)
Secondary Outcome
Measure Time Frame
Mean change in Hb value between Baseline and the secondary evaluation period Baseline visit, Week 52
Proportion of subjects with Hb values within the target range during the primary evaluation period Baseline visit, Week 36
AEs and SAEs Baseline visit to end of study (event-driven, minimum 1 year)
Proportion of time with Hb values within the target range during the primary evaluation period Baseline visit, Week 36
Proportion of time with Hb values within the target range during the secondary evaluation period Baseline visit, Week 52
Proportion of subjects with Hb values within the target range during the secondary evaluation period Baseline visit, Week 52
Proportion of subjects with Hb increase of >1.0 g/dL from Baseline visit From baseline visit to end of study (event-driven, minimum 36 weeks)
Time to achieve Hb increase of >1.0 g/dL from Baseline visit From baseline visit to end of study (event-driven, minimum 36 weeks)
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 Baseline visit, Week 36
Proportion of subjects receiving IV iron therapy Baseline visit, Week 52
Mean monthly dose of IV elemental iron administered in subjects who have received IV iron Baseline visit, Week 52
Proportion of subjects receiving RBC transfusion(s) Baseline visit, Week 52
Enrollment 369
Condition
Intervention

Intervention Type: Drug

Intervention Name: vadadustat

Description: oral tablet

Arm Group Label: Vadadustat

Other Name: AKB-6548

Intervention Type: Drug

Intervention Name: Darbepoetin alfa

Description: subcutaneous/intravenous

Arm Group Label: darbepoetin alfa

Other Name: aranesp

Eligibility

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Akebia Therapeutics Study Director Sponsor GmbH
Location
Facility:
Research Site | Huntsville, Alabama, 35805, United States
Research Site | Mesa, Arizona, 85210, United States
Research Site | Anaheim, California, 92801, United States
Research Site | Canyon Country, California, 91387, United States
Research Site | Downey, California, 90240, United States
Research Site | Glendale, California, 91204, United States
Research Site | Granada Hills, California, 91344, United States
Research Site | La Mesa, California, 91942, United States
Research Site | Long Beach, California, 92886, United States
Research Site | Los Angeles, California, 90022, United States
Research Site | Montebello, California, 90640, United States
Research Site | Monterey Park, California, 91754, United States
Research Site | Newhall, California, 91321, United States
Research Site #1 | Northridge, California, 91324, United States
Research Site #2 | Northridge, California, 91324, United States
Research Site | Riverside, California, 92503, United States
Research Site | Riverside, California, 92505, United States
Research Site | Sacramento, California, 95825, United States
Research Site | San Diego, California, 92115, United States
Research Site | San Dimas, California, 91773, United States
Research Site | Whittier, California, 90603, United States
Research Site | Arvada, Colorado, 80002, United States
Research Site | Westminster, Colorado, 80031, United States
Research Site | Stamford, Connecticut, 06902, United States
Research Site | Coral Gables, Florida, 33134, United States
Research Site | Coral Springs, Florida, 33071, United States
Research Site | Lauderdale Lakes, Florida, 33313, United States
Research Site | Miami Beach, Florida, 33140, United States
Research Site | Miami, Florida, 33125, United States
Research Site | Miami, Florida, 33150, United States
Research Site | Winter Park, Florida, 32789, United States
Research Site | Augusta, Georgia, 30904, United States
Research Site | Columbus, Georgia, 31904, United States
Research Site #2 | Lawrenceville, Georgia, 30046, United States
Research Site | Statesboro, Georgia, 30458, United States
Research Site | Meridian, Idaho, 83642, United States
Research Site | Takoma Park, Maryland, 20912, United States
Research Site | Roseville, Michigan, 48066, United States
Research Site | Kansas City, Missouri, 64111, United States
Research Site | Albuquerque, New Mexico, 87109, United States
Research Site | Astoria, New York, 11102, United States
Research Site | Winston-Salem, North Carolina, 27103, United States
Research Site | Philadelphia, Pennsylvania, 19106, United States
Research Site #1 | Chattanooga, Tennessee, 37408, United States
Research Site #2 | Chattanooga, Tennessee, 37408, United States
Research Site | Knoxville, Tennessee, 37923, United States
Research Site | Nashville, Tennessee, 37205, United States
Research Site | Arlington, Texas, 76015, United States
Research Site | El Paso, Texas, 79935, United States
Research Site | Houston, Texas, 77054, United States
Research Site | Houston, Texas, 77099, United States
Research Site | San Antonio, Texas, 78212-4740, United States
Research Site | San Antonio, Texas, 78229, United States
Research Site | Hampton, Virginia, 23666, United States
Research Site | Bahia Blanca, Buenos Aires, B8001HXM, Argentina
Research Site | Ciudad Autonoma Buenos Aires, Buenos Aires, C1181ACH, Argentina
Research Site | Junin, Buenos Aires, 6000, Argentina
Research Site | Pergamino, Buenos Aires, B2700CPM, Argentina
Research Site | Temperley, Buenos Aires, 1834, Argentina
Research Site | Cordoba, 5000, Argentina
Research Site | Corrientes, 3400, Argentina
Research Site | Salta, A4400AXO, Argentina
Research Site | San Luis, 5700, Argentina
Research Site | Fortaleza, Ceará, 60430-370, Brazil
Research Site | Belo Horizonte, Minas Gerais, 30150-221, Brazil
Research Site | Juiz de Fora, Minas Gerais, 36036-330, Brazil
Research Site | Curitiba, Paraná, 80010-030, Brazil
Research Site | Maringá, Paraná, 87060-040, Brazil
Research Site | Canoas, Rio Grande Do Sul, 92425-900, Brazil
Research Site | Passo Fundo, Rio Grande Do Sul, 99010-080, Brazil
Research Site | Porto Alegre, Rio Grande Do Sul, 90035-074, Brazil
Research Site | Porto Alegre, Rio Grande Do Sul, 90035-903, Brazil
Research Site | Joinville, Santa Catarina, 89202-050, Brazil
Research Site | Santo André, Sao Paulo, 09090-790, Brazil
Research Site | São Bernardo do Campo, Sao Paulo, 09715-090, Brazil
Research Site | São Paulo, Sao Paulo, 04039-000, Brazil
Research Site | Villingen-Schwenningen, Baden Wuerttemberg, 78054, Germany
Research Site | Rostock, Mecklenburg Vorpommern, 18057, Germany
Research Site | Duesseldorf, Nordrhein Westfalen, 40210, Germany
Research Site | San Giovanni Rotondo, Foggia, 71013, Italy
Research Site | Genova, 16132, Italy
Research Site | Lecco, 23900, Italy
Research Site | Napoli, 80138, Italy
Research Site | Pavia, 27100, Italy
Research Site | Roma, 168, Italy
Research Site | Siena, 53100, Italy
Research Site | Chuncheon, Gangwon-do, 200-702, Korea, Republic of
Research Site | Seongnam-si,, Gyeonggi-do, 13496, Korea, Republic of
Research Site | Busan, 47392, Korea, Republic of
Research Site | Seoul, 6591, Korea, Republic of
Research Site | Seoul, 7345, Korea, Republic of
Research Site | Zapopan, Jalisco, 45030, Mexico
Research Site | Morelia, Michoacán, 58260, Mexico
Research Site | Culiacan, Sinaloa, 80230, Mexico
Research Site | Golub Dobrzyn, 87-400, Poland
Research Site | Lodz, 90-153, Poland
Research Site | Lodz, 92-213, Poland
Research Site | Leiria, 2400-441, Portugal
Research Site | Loures, 2674-514, Portugal
Research Site #2 | Kemerovo, 650066, Russian Federation
Research Site | Krasnoyarsk, 660022, Russian Federation
Research Site | Moscow, 125466, Russian Federation
Research Site | Saint-Petersburg, 197022, Russian Federation
Research Site | Saint-Petersburg, 197110, Russian Federation
Research Site | St. Petersburg, 198205, Russian Federation
Research Site | St. Petersburg, 199004, Russian Federation
Research Site | Brovary, 7400, Ukraine
Research Site | Cherkassy, 18009, Ukraine
Research Site | Dnipro, 49005, Ukraine
Research Site | Ivano-Frankivsk, 76008, Ukraine
Research Site | Kharkiv, 61037, Ukraine
Research Site | Kyiv, 2125, Ukraine
Research Site | Mykolaiv, 54058, Ukraine
Research Site | Ternopil, 46002, Ukraine
Research Site | Uzhgorod, 88018, Ukraine
Research Site | Vinnytsia, 21018, Ukraine
Research Site | Zaporizhzhia, 69600, Ukraine
Research Site | Zhytomyr, 10002, Ukraine
Location Countries

Argentina

Brazil

Germany

Italy

Korea, Republic of

Mexico

Poland

Portugal

Russian Federation

Ukraine

United States

Verification Date

June 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Vadadustat

Type: Experimental

Label: darbepoetin alfa

Type: Active Comparator

Acronym INNO2VATE
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov