Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects

• Sponsor: Akebia Therapeutics (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04707768
• Collaborator: (none)
• Enrollment: 456
• Locations: 58
• Arms: 3
• Anticipated Duration (Months): 17.4
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will be conducted to demonstrate the efficacy and safety of vadadustat administered three times weekly (TIW) compared to a long-acting erythropoiesis-stimulating agent (ESA) (Mircera®) for the maintenance treatment of anemia in hemodialysis participants.

Condition or Disease	Intervention/Treatment	Phase
Anemia Associated With Chronic Kidney Disease (CKD)	Drug: Vadadustat; Drug: Mircera®	Phase 3

Detailed Description

Following randomization, there will be 2 periods during the study:

• Conversion and Maintenance Period (Weeks 0 to 52): conversion to vadadustat TIW or to remain on Mircera® (Weeks 0 to 20). There will be a primary efficacy evaluation period (Weeks 20 to 26) and a secondary efficacy evaluation period (Weeks 46 to 52).

• Safety Follow-up Period (Early Termination [ET] and Follow-Up): post-treatment safety follow-up visit (ET/End of Treatment [EOT] +4 weeks) either in person or via telephone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 456 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects
• Actual Study Start Date: Jul 21, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vadadustat low dose Participants previously receiving Mircera® will receive a low dose of vadadustat for up to 52 weeks.	Drug: Vadadustat; oral tablets
Experimental: Vadadustat high dose Participants previously receiving Mircera® will receive a high dose of vadadustat for up to 52 weeks.	Drug: Vadadustat; oral tablets
Active Comparator: Mircera® Participants will continue to receive Mircera® for up to 52 weeks.	Drug: Mircera®; intravenous administration

Outcome Measures

Primary Outcome Measures

1. Mean change in hemoglobin (Hb) between Baseline (average pretreatment Hb) and the primary evaluation period (average Hb from Weeks 20 to 26, inclusive) [Baseline; Weeks 20-26]

2. Number of participants with treatment-emergent non-serious adverse events and treatment-emergent serious adverse events [up to Week 56]

Secondary Outcome Measures

1. Mean change in Hb between Baseline (average pretreatment Hb) and the secondary evaluation period (average Hb from Weeks 46 to 52, inclusive) [Baseline; Weeks 46-52]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥18 years of age

• Receiving chronic, outpatient in-center hemodialysis three times weekly (TIW) for end-stage kidney disease for at least 12 weeks prior to Screening Visit 1 (SV1)

• Currently maintained on Mircera® with at least 2 doses received within 8 weeks prior to Screening Visit 2 (SV2)

• Mean Screening hemoglobin (Hb) between 8.5 and 11.0 grams per deciliter (g/dL) (inclusive), as determined by the average of 2 Hb values measured by the central laboratory at least 4 days apart between SV1 and SV2

• Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

• Folate and vitamin B12 measurements ≥ lower limit of normal during Screening

Exclusion Criteria:

• Anemia due to a cause other than chronic kidney disease (CKD) (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)

• Clinically meaningful bleeding event in opinion of Investigator within 8 weeks prior to Baseline

• Red blood cell (RBC) transfusion within 8 weeks prior to Baseline

• Having received any doses of darbepoetin alfa (Aranesp®) within 4 weeks prior to Baseline

• Having received any doses of epoetin alfa (Epogen®) within 1 week prior to Baseline

• Anticipated to discontinue hemodialysis during the study

• Judged by the Investigator that the participant is likely to need rescue therapy (erythropoiesis-stimulating agent [ESA] administration or RBC transfusion) immediately after enrollment in the study

• History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver)

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin >2 x upper limit of normal (ULN) during Screening. Participants with a history of Gilbert's syndrome are not excluded.

• Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of an ESA

• Acute coronary syndrome (hospitalization for unstable angina or 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 heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening

• History of new, active or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or treated cervical carcinoma in situ are not excluded.

• History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening

• History of hemosiderosis or hemochromatosis

• History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded)

• Scheduled organ transplant from a living donor and participants on the kidney transplant wait-list who are expected to receive a transplant within 6 months

• History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)

• Known hypersensitivity to vadadustat, Mircera®, or any of their excipients

• Use of an investigational medication or participation in an investigational study within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to Screening (participants may participate in another concurrent study only if that study is a non-interventional, observational investigation)

• Current exposure to any hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor or prior exposure to vadadustat

• Participants with bilateral native nephrectomy

• Noncompliance with dialysis session attendance defined as missing more than 1 dialysis session within 8 weeks prior to Baseline

• Active Severe Acute Respiratory Syndrome-Related Coronavirus (SARS CoV-2) during Screening

• Females who are pregnant or breastfeeding during Screening or are planning to become pregnant and breastfeeding during the study period, and for 30 days after the final study drug administration

• Women of childbearing potential who are unable or unwilling to use 2 acceptable methods of contraception starting at Screening, throughout the study period and for 45 days after the final study drug administration. Acceptable methods of contraception include (a.) established use of oral, injected, or implanted hormonal methods of contraception; (b.) placement of an intrauterine device or intrauterine system; (c.) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

• Female participants of childbearing potential who plan to donate ova during the study, and for 30 days after the last dose of study drug

• Non-vasectomized male participants who are unable or unwilling to use an acceptable method of contraception from time of first dose of study drug until 30 days after the last dose of the study drug

• Male participants who plan to donate sperm during the study and for at least 30 days after the last dose of study drug

• Any other reason, which in the opinion of the Investigator, would make the participant not suitable for participation in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Huntsville	Alabama	United States	35805
2	Research Site	Phoenix	Arizona	United States	85035
3	Research Site	Pine Bluff	Arkansas	United States	71603
4	Research Site	El Centro	California	United States	92243
5	Research Site	Escondido	California	United States	92025
6	Research Site	Fresno	California	United States	93720
7	Research Site	Granada Hills	California	United States	91344
8	Research Site	Porterville	California	United States	93257
9	Research Site	San Diego	California	United States	92111
10	Research Site	Arvada	Colorado	United States	80002
11	Research Site	Denver	Colorado	United States	80210
12	Research Site	Hockessin	Delaware	United States	19707
13	Research Site	Bradenton	Florida	United States	34209
14	Research Site	Coral Gables	Florida	United States	33134
15	Research Site#1	Coral Springs	Florida	United States	33071
16	Research Site#2	Coral Springs	Florida	United States	33071
17	Research Site	Jacksonville	Florida	United States	32216
18	Research Site	Athens	Georgia	United States	30606
19	Research Site	Buford	Georgia	United States	30518
20	Research Site	Dalton	Georgia	United States	30720
21	Research Site	Macon	Georgia	United States	31201
22	Research Site	Nampa	Idaho	United States	83687
23	Research Site	Baton Rouge	Louisiana	United States	70884
24	Research Site	Shreveport	Louisiana	United States	71101
25	Research Site	Plymouth	Massachusetts	United States	02360
26	Research Site	Springfield	Massachusetts	United States	01107
27	Research Site	Kalamazoo	Michigan	United States	49007
28	Research Site	Rochester Hills	Michigan	United States	48309
29	Research Site	Saint Clair Shores	Michigan	United States	48081
30	Research Site	Brookhaven	Mississippi	United States	39601
31	Research Site	Columbus	Mississippi	United States	39705
32	Research Site	Tupelo	Mississippi	United States	38801
33	Research Site	North Platte	Nebraska	United States	69101
34	Research Site	Las Vegas	Nevada	United States	89115
35	Research Site	Reno	Nevada	United States	89511
36	Research Site	Portsmouth	New Hampshire	United States	03801
37	Research Site	Albuquerque	New Mexico	United States	87109
38	Research Site	Gallup	New Mexico	United States	87301
39	Research Site	Charlotte	North Carolina	United States	28204
40	Research Site	Durham	North Carolina	United States	27704
41	Research Site	Kinston	North Carolina	United States	28504
42	Research Site	Raleigh	North Carolina	United States	27609
43	Research Site	Columbus	Ohio	United States	43215
44	Research Site	Kittanning	Pennsylvania	United States	16201
45	Research Site	Knoxville	Tennessee	United States	37923
46	Research Site	Arlington	Texas	United States	76015
47	Research Site	Austin	Texas	United States	78758
48	Research Site	Dallas	Texas	United States	75230
49	Research Site	Dallas	Texas	United States	75231
50	Research Site	Houston	Texas	United States	77074
51	Research Site	Houston	Texas	United States	77099
52	Research Site	Mansfield	Texas	United States	76063
53	Research Site	Mission	Texas	United States	78572
54	Research Site	San Antonio	Texas	United States	78211
55	Research Site	San Antonio	Texas	United States	78251
56	Research Site	Alexandria	Virginia	United States	22304
57	Research Site	Salem	Virginia	United States	24153
58	Research Site	Woodbridge	Virginia	United States	22192

Sponsors and Collaborators

• Akebia Therapeutics

Investigators

• Study Director: Chief Medical Officer, Akebia Therapeutics Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Akebia Therapeutics
• ClinicalTrials.gov Identifier: NCT04707768
• Other Study ID Numbers: AKB-6548-CI-0039
• First Posted: Jan 13, 2021
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Akebia Therapeutics: Anemia; Chronic Kidney Disease; CKD; Hemodialysis; Vadadustat; Erythropoiesis-stimulating agent (ESA)
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

No Results Posted as of Aug 22, 2022