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

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2012-002805-23-ES
• Date of registration: 09/01/2013
• Prospective Registration: Yes
• Primary sponsor: KAI Pharmaceuticals, Inc (a subsidiary of Amgen, Inc.)
• Public title: A study of AMG 416 in the treatment of secondary hyperparathyroidism in chronic kidney disease
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Assess the Efficacy and Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis
• Date of first enrolment: 22/02/2013
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002805-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Regulatory Affairs
• Affiliation: Amgen Limited

• Name: Regulatory Affairs
• Affiliation: Amgen Limited

Key inclusion & exclusion criteria

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 child-bearing potential must have a negative serum pregnancy test within 2 weeks prior to the first dose of investigational product.
? 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 receiving active vitamin D sterols must have had no more than a maximum dose change of 50% within the 2 months prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study.
? Subject receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 months prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable dose for the duration of the study.
? Subject receiving calcium supplements must have had no more than a maximum dose change of 50% within the 2 months 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 20% of subjects.
? Subject must have 2 consecutive screening predialysis serum cCa (Albumin corrected calcium concentration) 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
? Subject 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 entered this study.
? Subject has participated 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
? 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 non-melanoma 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 (eg, persistent or recurrent postdialysis systolic blood pressure (SBP) > 180 mmHg or DBP > 110 mmHg during the 3 months prior to screening).
? Subject has a history of 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 central laboratory tests during the 4 weeks 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
? Hemoglobin < 8.5 g/dL
? Platelet count < 100,000 x106/L
? 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 I

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

Secondary hyperparathyroidism in subjects with chronic kidney disease
MedDRA version: 14.1 Level: PT Classification code 10020708 Term: Hyperparathyroidism secondary System Organ Class: 10014698 - Endocrine disorders
MedDRA version: 14.1 Level: LLT Classification code 10020706 Term: Hyperparathyroidism NOS System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Product Name: AMG 416 (KAI-4169)
Product Code: AMG 416 (KAI-4169)
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: AMG 416
CAS Number: 1334237-71-6
Current Sponsor code: AMG 416
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Intravenous bolus use (Noncurrent)

Primary Outcome(s)

Main Objective: To evaluate the efficacy and safety of AMG 416 in the treatment of secondary hyperparathyroidism (SHPT) in subjects with chronic kidney disease (CKD) on hemodialysis.

Primary: To evaluate the efficacy of AMG 416 compared with placebo for reducing the serum intact parathyroid hormone level (iPTH) by > 30%.

Primary end point(s): Proportion of subjects with > 30% reduction from baseline in predialysis iPTH during the efficacy assessment phase

Timepoint(s) of evaluation of this end point: Throughout the efficacy assessment phase (Week 20 - Week 27 inclusive)

Secondary Objective: ? to evaluate the impact of AMG 416 compared with placebo on corrected calcium (cCa), corrected calcium-phosphorous 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

Secondary Outcome(s)

Secondary end point(s): - proportion of subjects with predialysis iPTH ? 300 pg/mL
- percent change from baseline in predialysis iPTH
- percent change from baseline in predialysis serum cCa (Albumin corrected calcium concentration)
- percent change from baseline in predialysis cCa x P (corrected calcium-phosphorous product)
- percent change from baseline in predialysis serum phosphorus

Timepoint(s) of evaluation of this end point: Fase de evaluación de la eficacia (período comprendido entre las semanas 20 y 27, ambas inclusive)

Secondary ID(s)

20120229(KAI-4169-006)

2012-002805-23-HU

Source(s) of Monetary Support

KAI Pharmaceuticals, Inc (a subsidiary of Amgen, Inc.)