UMIN-CTR Clinical Trial

Basic information
Public title	Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)
Acronym	Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)
Scientific Title	Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)
Scientific Title:Acronym	Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)
Region	Japan

Condition
Condition	Maintenance hemodialysis patients with secondary hyperparathyroidism
Classification by specialty	Endocrinology and Metabolism Nephrology Gastrointestinal surgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To compare the effects on serum calcification propensity (T50) between etercalcetide and vitamin D receptor activator (maxacalcitol) in the treatment of maintenance hemodialysis patients with secondary hyperparathyroidism
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Change in T50 (delta T50) at 12 month from baseline
Key secondary outcomes	1) Changes in T50 (delta T50) at 3 and 6 month from baseline 2) Proportions of participants who achieve the target ranges of serum Ca, P and intact PTH, respectively, by the JSDT CKD-MBD guideline (2012) at 3, 6 and 12 month 3) Proportions of participants who have the reduction of intact PTH level by 30% or greater at 3, 6 and 12 month 4) Ca-P product at 3, 6 and 12 month 5) Serum Fetuin A and FGF23 levels at 3, 6 and 12 month 6) Subjective symptoms (nausea, vomiting, cacogeusia, diarrhea, and jitteriness) 7) Hypocalcemia and hypercalcemia requiring cessation of the study drug 8) Severe adverse events in 12 months (all-cause death, hospitalization due to cardiovascular event, infection, and others) 9) Falls 12 months 10) Change in hand grip strength at 12 month from baseline 11) Changes in ability of daily living and cognitive function at 12 month from baseline

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Active
Stratification	YES
Dynamic allocation	NO
Institution consideration
Blocking
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Etelcalcetide (intravenous), thrice weekly, for 12 months. Starting dose, 5 mg (thrice weekly). Dose adjustment according to the package insert.
Interventions/Control_2	Maxacalcitol (intravenous), thrice weekly, for 12 months. Starting dose, 5 microg (thrice weekly) if intact PTH < 500 pg/mL; 10 microg (thrice weekly) if intact PTH >= 500 pg/mL. Dose adjustment according to the package insert.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1) Men and women, age >= 20 and < 80 years 2) Duration of dialysis >= 90 days 3) Serum intact PTH >= 241 pg/mL and corrected Ca >= 8.4 mg/dL, 4) Treated 3 times a week of hemodialysis 5) No treatment with etelcalcetide, cinacalcet, intravenous or oral vitamin D receptor activator in the preceding four weeks or longer
Key exclusion criteria	1) History of parathyroid intervention or fracture in the preceding 12 weeks 2) History of myocardial infarction, stroke, lower limb amputation, or revascularization for coronary artery or lower extremity in the preceding 12 weeks 3) Presence of heart failure of NYHA class III or IV 4) Presence of respiratory failure of SpO2 < 90% 5) Patients with severe illness with life expectancy of less than 1 year 6) Liver dysfunction with elevated AST or ALT exceeding 3 x upper limit of normal 7) Pregnant, lactating women or women who plan to be pregnant 8) History of allergy to etercalcetide and/or maxacalcitol 9) Patients treated with bisphosphonate and/or denosumab
Target sample size	400

Research contact person
Name of lead principal investigator	1st name Tetsuo Middle name Last name Shoji
Organization	Osaka City University Graduate School of Medicine
Division name	Department of Vascular Medicine
Zip code	545-8585
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
TEL	06-6645-3930
Email	t-shoji@med.osaka-cu.ac.jp

Public contact
Name of contact person	1st name Shinya Middle name Last name Nakatani
Organization	Osaka City University Graduate School of Medicine
Division name	Department of Metabolism, Endocrinology and Molecular Medicine
Zip code	545-8585
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
TEL	06-6645-3806
Homepage URL
Email	m2026719@med.osaka-cu.ac.jp

Sponsor
Institute	Osaka City University
Institute
Department

Funding Source
Organization	ONO PHARMACEUTICAL CO., LTD.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Ethical Committee of Osaka City University Graduate School of Medicine
Address	1-5-7, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
Tel	06-6645-3456
Email	ethics@med.osaka-cu.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

大阪市立大学医学部附属病院（大阪府）、医療法人蒼龍会 井上病院（大阪府）、特定医療法人仁真会 白鷺病院（大阪府）、特定医療法人仁真会 白鷺診療所（大阪府）、特定医療法人仁真会 白鷺北巽クリニック（大阪府）、特定医療法人仁真会 白鷺南クリニック（大阪府）、特定医療法人仁真会 藤井寺白鷺クリニック（大阪府）、医療法人寿楽会 大野記念病院（大阪府）、医療法人寿楽会 寿楽会クリニック（大阪府）、医療法人藤井会 石切生喜病院（大阪府）、医療法人藤井会 住道クリニック（大阪府）、社会医療法人景岳会 南大阪クリニック（大阪府）、医療法人垣谷会 明治橋病院（大阪府）、医療法人 淀井病院（大阪府）、 医療法人宝持会 池田病院（大阪府）、医療法人宝持会 いけだクリニック（大阪府）、医療法人岡田会 岡田クリニック（大阪府）、医療法人徳靖会 小尾クリニック（大阪府）、医療法人恵仁会 小野内科医院（大阪府）、特定医療法人三和会 永山クリニック（大阪府）、医療法人 佐々木内科クリニック（大阪府）、野崎クリニック（大阪府）、医療法人 河村クリニック（大阪府）、マリエ医院（大阪府）

Other administrative information
Date of disclosure of the study information	2018 Year 01 Month 01 Day

Related information
URL releasing protocol	https://jrct.niph.go.jp/re/reports/detail/9902
Publication of results	Published

Result
URL related to results and publications	https://jrct.niph.go.jp/re/reports/detail/9902
Number of participants that the trial has enrolled	326
Results	Etelcalcetide was more effective in increasing T50 than maxacalcitol in hemodialysis patients with secondary hyperparathyroidism. There was no difference in the effects on hand grip strength or cognition between of the two drugs.
Results date posted	2021 Year 02 Month 28 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2021 Year 03 Month 08 Day
Baseline Characteristics	The number of participants, sex, diabetic nephropathy, age, duration of hemodialysis, serum intact PTH, corrected calcium, and phosphate levels of the two groups in the full analysis set were as follows [percentage for categorical variables, median (interquartile range) for continuous variables]: < Etelcalcetide group > Total N 165, Men 110 (66.7%), Diabetic nephropathy 69 (41.8%), Age 66 (55-71) years, Duration of hemodialysis 6.2 (3.1-14.8) years, serum intact PTH 418 (313-563) pg/mL, corrected calcium 9.20 (8.80-9.60) mg/dL, phosphate 5.50 (4.60-6.20) mg/dL. < VDRA group > Total N 156, Men 98 (62.8%), Diabetic nephropathy 56 (35.9%), Age 66 (57-71) years, Duration of hemodialysis 7.1 (3.7-14.3) years, serum intact PTH 436 (338-600) pg/mL, corrected calcium 9.20 (8.88-9.50) mg/dL, phosphate 5.60 (4.88-6.62) mg/dL.
Participant flow	Enrollment was done at an expected pace. The target number of participants was 400, and 425 patients were provisionally enrolled. After washout of medication following provisional enrollment, 99 patients did not meet the eligibility criteria and excluded. The final number of enrolled patients was 326 (167 in the etelcalcetide group and 159 in the VDRA group). In the etelcalcetide group, 1 was excluded because of eligibility, and 1 was excluded because the patient declined to receive. The assigned treatments were received in 165 patients in the etelcalcetide group and in 159 patients in the VDRA group. Safety analysis set included 165 patients in the etelcalcetide group and 159 patients in the VDRA group. Full analysis set included 165 patients in the etelcalcetide group and 156 patients in the VDRA group. Per-protocol set included 164 patients in the etelcalcetide group and 155 patients in the VDRA group.
Adverse events	Safety evaluation was done in the safety analysis set (Etelcalcetide group N = 165, VDRA group N = 159). This study examined SAEs, symptoms (nausea, vomiting, dysgeusia, diarrhea, itching, irritability), falls, hypercalcemia requiring temporal cessation of study drug, and hypocalcemia requiring temporal cessation of study drug. The safety results were as indicated below: (1) SAEs: Etelcalcetide group 41 events (32 cases, 19.4%) VDRA group 70 events (44 cases, 27.7%) (2) Symptoms Nausea: Etelcalcetide group 11 events (9 cases, 5.5%) VDRA group 24 events (17 cases, 10.7%) Vomiting: Etelcalcetide group 10 events (8 cases, 4.8%) VDRA group 16 events (12 cases, 7.5%) Dysgeusia: Etelcalcetide group 7 events (4 cases, 2.4%) VDRA group 5 events (3 cases, 1.9%) Diarrhea: Etelcalcetide group 22 events (16 cases, 9.7%) VDRA group 10 events (7 cases, 4.4%) Itching: Etelcalcetide group 58 events (30 cases, 18.2%) VDRA group 72 events (38 cases, 23.9%) Irritability: Etelcalcetide group 20 events (15 cases, 9.1%) VDRA group 24 events (16 cases, 10.1%) (3) Falls: Etelcalcetide group 47 events (28 cases, 17.0%) VDRA group 38 events (27 cases, 17.0%) (4) Hypercalcemia-hypocalcemia requiring temporal cessation of study drug Hypercalcemia requiring temporal cessation of study drug Etelcalcetide group 0 events (0 cases, 0%) VDRA group 10 events (10 cases, 6.3%) Hypocalcemia requiring temporal cessation of study drug Etelcalcetide group 33 events (30 cases, 18.2%) VDRA group 0 events (0 cases, 0%) Among the above (1) through (4), hypercalcemia-hypocalcemia requiring cessation of study drug was adjudicated to be related to study drugs, whereas the SAEs, symptoms, or falls were not considered to be related to study drugs.
Outcome measures	The primary, secondary and tertiary outcomes were the change in T50 (deltaT50), the changes in hand grip strength, and the change in cognition-ADL assessed by DASC-21 in 12 months of treatment, and these outcomes were compared between the etelcalcetide group (Intervention group) and the intravenous VDRA (maxacalcitol, Control group). deltaT50 was significantly greater in the etelcalcetide group, with the difference of 20 (7 to 34) minutes [difference (95% confidence interval), P = 0.004]. No significant difference was found in the change in hand grip strength [0.16 (-0.87 to 1.10) kg, P = 0.756] or in the DASC-21 score [-0.55 (-1.58 to 0.47) points, P = 0.291] between the two groups.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 09 Month 29 Day
Date of IRB	2017 Year 11 Month 27 Day
Anticipated trial start date	2018 Year 02 Month 01 Day
Last follow-up date	2020 Year 01 Month 09 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	The results of this trial have been published online on March 8, 2021: https://cjasn.asnjournals.org/content/early/2021/03/05/CJN.16601020

Management information
Registered date	2017 Year 12 Month 29 Day
Last modified on	2021 Year 03 Month 10 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034980