| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Chronic Kidney Disease
Secondary Hyperparathyroidism (SHPT) |
|
| E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney Disease
Secondary Hyperparathyroidism (SHPT) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064848 |
| E.1.2 | Term | Chronic kidney disease |
| E.1.2 | System Organ Class | 100000004857 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020708 |
| E.1.2 | Term | Hyperparathyroidism secondary |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Demonstrate that treatment with AMG 416 is not inferior to treatment with cinacalcet for lowering plasma 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. |
|
| E.2.2 | Secondary objectives of the trial |
| Treatment with AMG 416 is superior to treatment with cinacalcet as measured by the proportion of subjects with > 50% decrease in pre-dialysis serum PTH from baseline, by the proportion of subjects with > 30% decrease in pre-dialysis serum PTH from baseline, and by the mean days of vomiting or nausea per week in the first 8 weeks, change from baseline in albumin corrected calcium concentration (cCa), mean pre-dialysis serum phosphorous (P), mean severity of nausea, and mean episodes of vomiting per week. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Subject has provided informed consent.
- Subject is 18 years of age or older.
- Female subject must be willing to use highly effective contraception during the study and for 3 months after the last dose of investigational product (unless postmenopausal or surgically sterilized).
- 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 (URR) ≥ 65% within 4 weeks prior to screening laboratory assessments.
- Dialysate calcium concentration must be ≥ 2.5 mEq/L and stable for at least 4 weeks prior to screening laboratory assessments, and must remain ≥ 2.5 mEq/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.
- Subject must have one 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 maximum 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. |
|
| E.4 | Principal exclusion criteria |
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
- Currently receiving other investigational procedures while participating in this study are excluded.
- Subject has received AMG 416 in a prior clinical trial of AMG 416 (also known as KAI-4169).
- 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 AMG 416 to be administered during dosing.
- Subject has previously been randomized 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 (except non-melanoma skin cancers or cervical carcinoma in situ).
- Subject is pregnant or nursing.
- 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 < 2.5 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]) > 2.5 times the upper limit of normal (ULN) at screening
- Subject likely to not be 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. This includes a subject who previously received cinacalcet, and in the opinion of the Investigator, is not a good candidate for future cinacalcet treatment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Achievement of a > 30% reduction from baseline in mean pre-dialysis serum plasma PTH level during the efficacy assessment phase (EAP). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At day 20, 22, 24, 26 and 27 |
|
| E.5.2 | Secondary end point(s) |
Key Secondary Endpoints:
- achievement of a > 50% reduction from baseline in mean pre-dialysis serum PTH during the EAP
- achievement of a > 30% reduction from baseline in mean pre-dialysis serum PTH during the EAP (superiority)
- mean number of days of vomiting or nausea per week in the first 8 weeks
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Information about nausea and vomiting will be collected via a patient reported outcome instrument.
- At day 20, 22, 24, 26 and 27 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 115 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Austria |
| Belgium |
| Canada |
| Czech Republic |
| Denmark |
| Estonia |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Latvia |
| Lithuania |
| Poland |
| Portugal |
| Russian Federation |
| Spain |
| Sweden |
| Switzerland |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the entire study for all subjects occurs at the primary completion date, which is defined as the time when the last subject completes their end of study visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 15 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 15 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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