Clinical Trials Register

Summary
EudraCT Number:	2012-002808-41
Sponsor's Protocol Code Number:	20120231(KAI-4169-008)
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2012-002808-41

A.3

Full title of the trial

A Multicenter Single-arm Extension Study to Describe the Long-term
Efficacy and Safety of AMG 416 in the Treatment of Secondary
Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

Estudio de extensión, multicéntrico y de un solo grupo, para describir la eficacia y la seguridad a largo plazo de AMG 416 en el tratamiento del hiperparatiroidismo secundario en pacientes con insuficiencia renal crónica sometidos a hemodiálisis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of AMG 416 in the treatment of secondary hyperparathyroidism in chronic kidney disease

Estudio de AMG 416 en el tratamiento de hiperparatiroidismo secundario en pacientes con insuficiencia renal crónica

A.4.1

Sponsor's protocol code number

20120231(KAI-4169-008)

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	KAI Pharmaceuticals, Inc. (a subsidiary of Amgen, Inc.)
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	KAI Pharmaceuticals, Inc. (a subsidiary of Amgen, Inc.)
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amgen Limited
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	240 Cambridge Science Park, Milton Road
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB4 0WD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441895525 585
B.5.5	Fax number	001805480 9385
B.5.6	E-mail	lhurd@amgen.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AMG 416 (KAI-4169)
D.3.2	Product code	AMG 416 (KAI-4169)
D.3.4	Pharmaceutical form	Powder for solution for injection or infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AMG 416
D.3.9.1	CAS number	1334237-71-6
D.3.9.2	Current sponsor code	AMG 416
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Secondary hyperparathyroidism in subjects with chronic kidney disease

Hiperparatiroidismo secundario en pacientes con insuficiencia renal crónica

E.1.1.1

Medical condition in easily understood language

Hyperparathyroidism (high levels of parathyroid hormone) secondary to chronic kidney disease

Hiperparatiroidismo (niveles elevados de hormona paratiroidea) secundario a la insuficiencia renal crónica

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	15.1
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	15.1
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To characterize the long-term safety and tolerability of AMG 416 in the treatment of SHPT in subjects with chronic kidney disease on hemodialysis.

Caracterizar la seguridad y la tolerabilidad a largo plazo de AMG 416 en el tratamiento del HPTS en pacientes con insuficiencia renal crónica sometidos a hemodiálisis

E.2.2

Secondary objectives of the trial

Secondary objectives are to characterize the long-term efficacy of AMG 416 on intact parathyroid hormone (iPTH), corrected calcium (cCa), corrected calcium-phosphorus product (cCa x P), and phosphorus

Los objetivos secundarios son caracterizar la eficacia a largo plazo de AMG 416 sobre la hormona paratiroidea intacta (PTHi), la calcemia corregida (Cac), el producto entre la calcemia corregida y el fósforo (Cac x P) y el fósforo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
? Subject must complete the treatment and follow-up period, or have been discontinued for rising iPTH, from an AMG 416 phase 3 parent study prior to the start of dosing in this study.
? Subject agrees to not participate in another study of an investigational agent during the study.
? Dialysis prescription dialysate calcium concentration must be ? 2.25 mEq/L.
? Female subject who is post menopausal (post menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, has a medical condition that prevents pregnancy, remains abstinent, or is willing to use highly effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential must
have a negative serum pregnancy test within 2 weeks prior to the first dose of AMG 416.
? Male subject is willing to use highly effective contraception when sexually active and will not donate sperm during the treatment phase and for 3 months after the last dose.
? 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.

? El sujeto comprende los procedimientos del estudio y acepta participar en él dando su consentimiento informado por escrito.
? Antes de empezar el tratamiento del estudio, el sujeto habrá completado el tratamiento y el período de seguimiento o se habrá retirado de uno de los estudios originales de AMG416 Fase III debido a una elevación de la PTHi.
? El sujeto se compromete a no participar durante el estudio en ningún otro estudio de un fármaco en investigación.
? La concentración de calcio en el líquido de diálisis prescrita para la diálisis debe ser ? 2,25 mEq/l.
? Mujeres posmenopáusicas (con ausencia de menstruación durante el año precedente y mayores de 50 años), sometidas a esterilización quirúrgica, con un trastorno médico que impida el embarazo, que no mantienen relaciones sexuales o que están dispuestas a utilizar métodos anticonceptivos sumamente eficaces durante el estudio y hasta tres meses después de la última dosis. Las mujeres en edad fértil deben tener un resultado negativo en la prueba de embarazo en suero en las dos semanas previas a la primera dosis de AMG 416.
? Los varones deben estar dispuestos a utilizar un método anticonceptivo de gran eficacia cuando mantengan relaciones sexuales y no donarán semen durante la fase de tratamiento y hasta tres meses después de la última dosis.
? El representante legal del sujeto ha otorgado su consentimiento informado en el caso de que éste presente un trastorno de cualquier tipo que, en opinión del investigador, pueda afectar a su capacidad para dar el consentimiento informado por escrito.

E.4

Principal exclusion criteria

? Currently receiving treatment in another investigational device or drug study.
? Currently receiving other investigational procedures while participating in this study.
? Subject has known sensitivity to any of the products or components to be administered during dosing.
? Subject has received cinacalcet between the last dose of investigational product in the parent study (20120229 or 20120230) and the start of dosing with AMG 416 in the current 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 has a serious concurrent medical condition (eg, malignancy) likely to result in death during the next 12 months.
? Subject is pregnant or nursing.
? 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.

? Actualmente en tratamiento en otro estudio de un dispositivo o fármaco en investigación.
? Estar sometiéndose a otros procedimientos experimentales durante la participación en este estudio.
? El sujeto tiene sensibilidad conocida a alguno de los productos o componentes que se vayan a administrar durante el tratamiento del estudio.
? El sujeto ha recibido cinacalcet entre la última dosis del producto en investigación en el estudio original (20120229 0 20120230) y el comienzo de la administración de AMG 416 en el presente estudio.
? El sujeto padece una enfermedad inestable de acuerdo con la historia clínica, la exploración física y los análisis clínicos habituales, o se encuentra inestable en opinión del investigador.
? El sujeto tiene antecedentes de cualquier enfermedad que, en opinión del investigador, puede confundir los resultados del estudio o suponer un riesgo adicional para el sujeto.
? El sujeto tiene una enfermedad concomitante grave (por ejemplo, neoplasia maligna) que probablemente cause la muerte en los próximos 12 meses.
? La paciente está embarazada o en período de lactancia.
? Antecedentes o signos de cualquier anomalía, trastorno o enfermedad de importancia clínica (a excepción de los descritos anteriormente) que, en opinión del investigador o del médico de Amgen, en el caso de que se le consulte, suponga un riesgo para la seguridad del sujeto o pueda interferir en la evaluación, los procedimientos o la compleción del estudio.

E.5 End points

E.5.1

Primary end point(s)

? nature, frequency, severity, and relationship to treatment of all adverse events reported throughout the study
? vital signs and changes in laboratory parameters, including clinical chemistry
? evaluation of antibody formation to AMG 416

? naturaleza, frecuencia, intensidad y relación con el tratamiento de todos los acontecimientos adversos notificados durante el estudio.
? constantes vitales y alteraciones en los parámetros analíticos, incluida la bioquímica clínica.
? evaluación de la formación de anticuerpos anti-AMG 416.

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the efficacy assessment phase

Durante la fase de valoración de la eficacia

E.5.2

Secondary end point(s)

? proportion of subjects with > 30% reduction from baseline in predialysis iPTH during the efficacy assessment phase (EAP) and the EAP at 12 months (EAP12)
? proportion of subjects with predialysis iPTH ? 300 pg/mL during the EAP and EAP12
? percent change from baseline in predialysis iPTH during the EAP and EAP12
? percent change from baseline in predialysis serum cCa during the EAP and EAP12
? percent change from baseline in predialysis cCa x P during the EAP and EAP12
? percent change from baseline in predialysis serum phosphorus during the EAP and EAP12

? porcentaje de sujetos que presentan, durante la fase de evaluación de la eficacia (FEE) y la FEE a los 12 meses (FEE12), una reducción de la concentración de PTHi anterior a la diálisis mayor del 30% con respecto al período basal.
? porcentaje de sujetos con una concentración de PTHi anterior a la diálisis inferior o igual a 300 pg/ml durante la FEE y la FEE12.
? variación porcentual, con respecto al valor basal, de la PTHi anterior a la diálisis durante la FEE y la FEE12.
? variación porcentual, con respecto al valor basal, del Cac sérico anterior a la diálisis durante la FEE y la FEE12.
? variación porcentual, con respecto al valor basal, del producto Cac x P anterior a la diálisis durante la FEE y la FEE12.
? variación porcentual, con respecto al valor basal, del fósforo sérico anterior a la diálisis durante la FEE y la FEE12.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the efficacy assessment phase

Durante la fase de valoración de la eficacia

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised