E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary hyperparathyroidism in subjects with chronic kidney disease |
|
E.1.1.1 | Medical condition in easily understood language |
Hyperparathyroidism (high levels of parathyroid hormone) secondary to chronic kidney disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020706 |
E.1.2 | Term | Hyperparathyroidism NOS |
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 |
To evaluate the efficacy of AMG 416 compared with placebo for reducing the serum intact parathyroid hormone level (iPTH) by > 30% |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the impact of AMG 416 compared with placebo on
corrected calcium (cCa), corrected calcium-phosphorus product (cCa x P), and phosphorus
Safety objectives
• to assess the safety and tolerability of AMG 416 compared with placebo
Exploratory objectives
• to evaluate the pharmacokinetics (PK) of AMG 416
• to characterize the effect of multiple doses of AMG 416 on FGF-23 levels
• to characterize the effect of multiple doses of AMG 416 on bone specific alkaline phosphatase levels (BSAP)
• to characterize the effect of multiple doses of AMG 416 on tartrate resistant acid phosphatase-5b (TRAP5b) levels |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
• Subject is 18 years of age or older.
• Female subjects who are post menopausal (post menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, remain abstinent, or are willing to use highly effective contraception during the study and for 3 months after the last dose. Women of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to the first dose of investigational product.
• Subject receiving active 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 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.
• Subject receiving calcium supplements must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments and remain stable through randomization.
• Subject must be receiving hemodialysis 3 times weekly for at least 3 months and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks prior to screening laboratory assessments.
• Dialysis prescription dialysate calcium concentration must be ≥ 2.25 mEq/L and stable for at least 4 weeks prior to screening laboratory assessments, remain stable through randomization and remain ≥ 2.25 mEq/L for the duration of the study.
• Subject must have 2 consecutive screening predialysis serum iPTH labs drawn on separate days within 2 weeks prior to randomization and the results of both must be > 400 pg/mL. Enrollment of subjects with mean screening iPTH > 1000 pg/mL will be limited to no more than approximately 20% of subjects.
• Subject must have 2 consecutive screening predialysis serum cCa labs drawn on separate days within 2 weeks prior to randomization and the results of both must be ≥ 8.3 mg/dL.
• Subject agrees to not participate in another study of an investigational agent during the study.
• Subject's legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent. |
|
E.4 | Principal exclusion criteria |
• Currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(s) within 8 weeks prior to screening.
• Other investigational procedures while participating in this study are excluded.
• Anticipated or scheduled parathyroidectomy during the study period.
• Subject has received a parathyroidectomy within 3 months prior to dosing.
• Anticipated or scheduled kidney transplant during the study period.
• Subject has known sensitivity to any of the products or components to be administered during dosing.
• Subject has previously been randomized in this study.
• Subject has received AMG 416 in a prior clinical trial of AMG 416 (also referred to as KAI-4169).
• Subject has received cinacalcet within the 4 weeks prior to screening labs (treatment with cinacalcet is prohibited during the study).
• 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.
• Subject has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
• Subject history of malignancy within the last 5 years (except nonmelanoma skin cancers, or cervical carcinoma in situ).
• Subject has a serious concurrent medical condition (eg, malignancy) likely to result in death during the next 12 months.
• Subject is pregnant or nursing.
• Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes.
• Subject's screening 12-lead electrocardiogram (ECG) suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion.
• Subject has a history of poorly controlled hypertension.
• Subject has a history within the past 6 months of either angina pectoris with symptoms that occur at rest or minimal activity or a history of congestive heart failure (New York Heart Association Classification III or IV).
• Subject has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening.
• Subject is receiving treatment for a seizure disorder or has a history of a seizure within the last 12 months prior to screening.
• Subject has had surgery (except minor surgery) within the last 8 weeks 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]) > 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with > 30% reduction from baseline in predialysis iPTH during the efficacy assessment phase (EAP) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the EAP (Week 20 - Week 27 inclusive) |
|
E.5.2 | Secondary end point(s) |
• proportion of subjects with predialysis iPTH ≤ 300 pg/mL during the EAP
• percent change from baseline in predialysis iPTH during the EAP
• percent change from baseline in predialysis serum cCa during the EAP
• percent change from baseline in predialysis cCa x P during the EAP
• percent change from baseline in predialysis serum phosphorus during the EAP |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the EAP (Week 20 - Week 27 inclusive) |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
Belgium |
Canada |
France |
Italy |
Austria |
Netherlands |
Sweden |
Australia |
Czech Republic |
Germany |
Hungary |
Spain |
Israel |
Poland |
Russian Federation |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |