Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Head-to-Head Study of Etelcalcetide and Cinacalcet in Asian HD Subjects With SHPT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03299244
Recruitment Status : Recruiting
First Posted : October 3, 2017
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
To demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum intact parathyroid hormone (PTH) levels by > 30% from baseline among subjects with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.

Condition or disease Intervention/treatment Phase
Secondary Hyperparathyroidism Chronic Kidney Disease Drug: Etelcalcetide Drug: Cinacalcet Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 660 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Subjects will be randomized by IVR/IWR in a 1:1 ratio to either TIW IV etelcalcetide (and daily oral placebo tablets) or daily oral cinacalcet tablets (and TIW IV placebo) in a double-blind, double-dummy manner. Treatment groups will be blinded to the investigator, subjects, and the Amgen study team.
Primary Purpose: Treatment
Official Title: Multiple-dose, Double-blind, Double-dummy Study to Compare the Efficacy and Safety of Oral Doses of Cinacalcet Hydrochloride With Intravenous Doses of Etelcalcetide in Asian Hemodialysis Subjects With Secondary Hyperparathyroidism
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : April 13, 2020
Estimated Study Completion Date : April 13, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Etelcalcetide
Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and the dose may be titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
Drug: Etelcalcetide

Administered intravenously three times per week. The starting dose was 5 mg, titrated up to 15 mg based on serum PTH and corrected calcium levels.

Drug: Oral Placebo. Administered orally once a day.

Other Name: AMG416

Active Comparator: Cinacalcet
Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and the dose may be titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.
Drug: Cinacalcet

Cinacalcet was administered orally once a day. The starting dose was 25 mg daily, titrated up to 100 mg daily based on serum PTH and corrected calcium levels.

Drug: Intravenous Placebo Administered intravenously (IV) three times per week.

Other Name: Sensipar®, Mimpara®




Primary Outcome Measures :
  1. >30% reduction predialysis serum PTH [ Time Frame: weeks 20 to 27 ]
    The primary endpoint of the study is achievement of a > 30% reduction from baseline in mean predialysis serum PTH level during the Efficiency Assessment Phase (EAP) of the study (EAP is defined as weeks 20 to 27, inclusive).


Secondary Outcome Measures :
  1. > 50% reduction predialysis serum PTH [ Time Frame: weeks 20 to 27 ]
    Achievement of a > 50% reduction from baseline in mean predialysis serum PTH during the EAP (superiority)

  2. >30% reduction predialysis serum PTH [ Time Frame: weeks 20 to 27 ]
    Achievement of a > 30% reduction from baseline in mean predialysis serum PTH during the EAP (superiority)

  3. Percent change from baseline in mean predialysis serum cCa [ Time Frame: weeks 20 to 27 ]
    Percent change from baseline in mean predialysis serum cCa during the EAP

  4. Serum P ≤ 4.5 mg/dL during the EAP [ Time Frame: weeks 20 to 27 ]
    Achievement of mean predialysis serum P ≤ 4.5 mg/dL during the EAP


Other Outcome Measures:
  1. Percent change from baseline in mean predialysis P during the EAP [ Time Frame: weeks 20 to 27 ]
    Percent change from baseline in mean predialysis P during the EAP

  2. Serum PTH ≤ 300 pg/mL [ Time Frame: weeks 20 to 27 ]
    Achievement of mean predialysis serum PTH ≤ 300 pg/mL during the EAP

  3. Change in BSAP from baseline [ Time Frame: weeks 20 to 27 ]
    Change in serum bone specific alkaline phosphatase (BSAP) from baseline to week 27

  4. Change in C-telopeptide (CTX) from baseline [ Time Frame: weeks 20 to 27 ]
    Change in C-telopeptide (CTX) from baseline to week 27



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has provided informed consent prior to performing any study-related activities/procedures.
  • Male or female subjects ≥ 18 years of age or older at the time of signing informed consent.
  • Subject must be receiving maintenance hemodialysis 3 times weekly for at least 3 months, with adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio ≥ 65% within 4 weeks prior to screening laboratory assessments. The Kt/V formula used for a subject must be the formula used during routine care prior to screening.
  • Dialysate calcium concentration must be ≥ 2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to screening laboratory assessments, and must remain ≥ 2.5 mEq/L (1.25 mmol/L) for the duration of the study.
  • Subject must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, within 2 weeks prior to randomization.
  • Subject currently receiving vitamin D sterols must have had no more than a maximum dose change of 50% within the 4 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol or for safety reasons.
  • Subject must have 1 screening predialysis serum cCa laboratory value ≥ 8.3 mg/dL measured within 2 weeks prior to randomization.
  • A subject receiving calcium supplements must have had no more than a máximum dose change of 50% within 2 weeks prior to screening laboratory assessments and remain stable through randomization.
  • A subject receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol or for safety reasons.

Exclusion Criteria:

  • Currently receiving treatment in another investigational device or drug study, or ≤ 30 days since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded.
  • Subject has received etelcalcetide in a prior clinical trial of etelcalcetide.
  • Subject has received cinacalcet during the 3 months prior to the first screening laboratory assessments.
  • Subject has known sensitivity to any of the products or components of either cinacalcet or etelcalcetide to be administered during dosing.
  • Subject has previously been randomized in this study.
  • Anticipated or scheduled parathyroidectomy during the study period.
  • Subject has received a parathyroidectomy within 6 months prior to dosing.
  • Anticipated or scheduled kidney transplant during the study period.
  • Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.
  • Malignancy within the last 5 years of screening (except non-melanoma skin cancers or cervical carcinoma in situ).
  • Grapefruit juice is prohibited.
  • Subject is pregnant or nursing, or planning to become pregnant or nurse during treatment or within 3 months after the last dose of etelcalcetide or 30 days after the last dose of cinacalcet
  • Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product (IP) through 3 months after the last dose of IP.
  • Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes.
  • Subject has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening.
  • Subject has clinically significant abnormalities on prestudy clinical examination or abnormalities on the most recent central laboratory tests during the screening period prior to randomization according to the Investigator including but not limited to the following:

    • serum albumin < 3.0 g/dL
    • serum magnesium < 1.5 mg/dL
    • serum transaminase (alanine transaminase [ALT] or Serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT])> 3 times the upper limit of normal (ULN) at screening.
  • Subject likely not available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03299244


Contacts
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

  Show 86 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen

Additional Information:
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03299244     History of Changes
Other Study ID Numbers: 20150238
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Neoplasm Metastasis
Renal Insufficiency, Chronic
Hyperparathyroidism
Hyperparathyroidism, Secondary
Urologic Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Renal Insufficiency
Parathyroid Diseases
Endocrine System Diseases
Calcium
Cinacalcet
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Calcimimetic Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists