E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Kidney Disease
Secondary Hyperparathyroidism (SHPT) |
Nefropatia cronica - Iperparatiroidismo secondario (SHPT) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney Disease
Secondary Hyperparathyroidism (SHPT) |
Nefropatia cronica
Iperparatiroidismo secondario (SHPT)
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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 | 14.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 |
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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. |
Obiettivo principale:
Dimostrare che il trattamento con AMG 416 non è inferiore a quello con cinacalcet per ottenere una riduzione >30% rispetto al basale dei livelli sierici di ormone paratiroideo (PTH) intatto in soggetti con CKD e SHPT che richiedono il trattamento con l’emodialisi
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E.2.2 | Secondary objectives of the trial |
Assess whether treatment with AMG 416 is superior to treatment with cinacalcet as measured by the mean days of vomiting or nausea per week, proportion of subjects with > 50% decrease in plasma PTH from baseline, change from baseline in albumin corrected calcium concentration (cCa), mean pre-dialysis serum phosphorous (P), mean severity of nausea, and mean episodes of vomiting. Information about nausea and vomiting will be collected via a patient reported outcome. |
Obiettivi secondari:
Valutare se il trattamento con AMG 416 è superiore al trattamento con cinacalcet in termini di numero medio di giorni con vomito o nausea in una settimana, percentuale di soggetti con riduzione del PTH sierico >50% rispetto al basale, variazione rispetto al basale della concentrazione di calcio corretto per albumina (cCa), fosforo (P) sierico medio predialisi, gravità media della nausea e numero medio di episodi di vomito in una settimana. Le informazioni su nausea e vomito saranno raccolte mediante uno strumento di registrazione dell’outcome compilato dal paziente.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject has provided informed consent.
- 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.
- 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).
- Male subject must be willing to use highly effective contraception during the
- 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 3 months 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 having 2 consecutive central laboratory screening predialysis plasma PTH values > 600 pg/mL, measured on separate days within 4 weeks prior to randomization.
• For a subject currently receiving vitamin D sterols, the vitamin D dose must have been constant with no change for a minimum of 4 weeks prior to screening laboratory assessments and until randomization.
- Subject must have 2 consecutive screening predialysis serum cCa laboratory values measured on separate days within 4 weeks prior to randomization, and the results on both days must be ≥ 8.3 mg/dL.
- A subject receiving calcium supplements must be on a stable dose for at least 2 weeks prior to screening laboratory assessments and until randomization.
- A subject receiving phosphate binders must be on a stable dose for at least 2 weeks prior to screening laboratory assessments and dose should remain stable throughout the study except as noted in the protocol. |
I soggetti eleggibili devono essere in trattamento con emodialisi di mantenimento adeguata (si veda alla Sezione 4.1.6 del protocollo) tre volte a settimana, con una concentrazione di calcio nel dialisato ≥2,5 mEq/L, da almeno 3 mesi al momento della valutazione degli esami di laboratorio.
• I soggetti devono avere SHPT definito in presenza di 2 riscontri consecutivi mediante screening presso il laboratorio centrale di livelli sierici predialisi di PTH >600 pg/mL, valutati in due giorni separati nelle 4 settimane precedenti la randomizzazione.
o Nei soggetti attualmente trattati con steroli della vitamina D, il dosaggio di tale vitamina deve essere costante senza alterazioni da almeno 4 settimane prima della randomizzazione.
• I soggetti devono avere livelli di cCa sierico ≥8,3 mg/dL, rilevati in 2 misurazioni di screening consecutive ottenute prima della dialisi in giorni distinti entro 4 settimane dalla data della randomizzazione.
• I soggetti che ricevono integrazioni di calcio devono essere trattati con dosaggi stabili da almeno 2 settimane prima delle valutazioni degli esami di laboratorio e tali regimi devono rimanere invariati fino alla randomizzazione.
• I soggetti che ricevono leganti dei fosfati devono essere trattati con dosaggi stabili da almeno 2 settimane prima delle valutazioni degli esami di laboratorio e tali regimi devono rimanere invariati per tutta la durata dello studio, fatta eccezione per i casi descritti nel protocollo.
• I soggetti eleggibili non devono aver ricevuto cinacalcet nei 3 mesi precedenti la prima valutazione degli esami di laboratorio.
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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 participated 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 entered this study previously.
- 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 central laboratory tests during the 4 weeks 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. |
Attualmente in cura con un altro dispositivo sperimentale o farmaco
- in studio, o meno di 30 giorni dalla conclusione del trattamento con un altro dispositivo sperimentale o farmaco
- In fase di ricezione di altre procedure di sperimentazione,
- Il soggetto ha partecipato ad uno studio clinico preliminare di AMG 416 (noto anche
come KAI-4169).
- Il soggetto ha ricevuto cinacalcet durante i 3 mesi precedenti il primo screening per valutazioni di laboratorio.
- Il soggetto ha avuto reazioni allergiche a uno qualsiasi dei prodotti o componenti di cinacalcet o AMG 416.
- Il soggetto ha partecipato a questo studio precedentemente.
- Anticipata o prevista paratiroidectomia durante il periodo di studio.
- Il soggetto ha avuto una paratiroidectomia nei 6 mesi precedenti alla fase di dosaggio.
- previsto, o in lista, per trapianto di rene durante il periodo di studio.
- Il soggetto ha una condizione medica instabile in base alla storia clinica, esame fisico ed esami di laboratorio di routine, o è altrimenti instabile a giudizio dello sperimentatore.
- Tumore maligno negli ultimi 5 anni (ad eccezione di carcinoma non-melanoma o cervicale in situ).
- Il soggetto è in stato di gravidanza o allattamento.
- Il soggetto ha una storia di aritmie ventricolari sintomatiche o Torsione di punta.
- Il soggetto ha una storia di infarto miocardico, angioplastica coronarica, o bypass arterioso coronarico e innesto negli ultimi 6 mesi precedenti lo screening.
- Il soggetto presenta alterazioni clinicamente significative negli esami di pre-studio o test di laboratorio centrale durante le 4 settimane precedenti la randomizzazione secondo l'investigatore, compreso ma non limitato ai seguenti:
• albumina sierica <2,5 g / dL
• magnesio sierico <1,5 mg / dl
• siero transaminasi (alanina transaminasi [ALT] o siero glutammico piruvico transaminasi [SGPT], aspartato aminotransferasi [AST] o sierica glutammico-ossalacetico transaminasi SGOT [])> 2,5 volte il superiore
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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). |
Raggiungimento di una riduzione >30% dei livelli sierici medi predialisi di PTH rispetto al basale durante la fase di valutazione dell’efficacia (EAP) dello studio (la fase EAP corrisponde alle settimane 20-27). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At day 20, 22, 24, 26 and 27 |
Al giorno 20, 22, 24, 26 and 27 |
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E.5.2 | Secondary end point(s) |
- mean number of days of vomiting or nausea per week in the first 8 weeks
- achievement of a > 50% reduction from baseline in mean pre-dialysis plasma PTH during the EAP |
- numero medio di giorni di vomito o nausea in una settimana nelle prime 8 settimane
- raggiungimento di una riduzione >50% rispetto al basale dei livelli sierici medi predialisi di PTH durante la EAP
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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 |
- Informazioni su nausea e vomito saranno raccolte attraverso uno strumento esito riportato paziente
- Al giorno 20,22,24,26 e 27 |
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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 | 7 |
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 |
Austria |
Belgium |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
United Kingdom |
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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
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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. |
La fine dell'intero studio per tutti i soggetti si verifica alla data di completamento primario, che è definita come il tempo in cui l'ultimo soggetto completa l’ultima visita dello studio. |
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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 |