Clinical trial NCT03283098: A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416
Official title: A Phase 1, Multiple Dose, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pharmacokinetics, Safety and Tolerability of AMG 416 Administered Intravenously to Chinese Subjects With Chronic Kidney Disease on Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Secondary Hyperparathyroidism
Keywords: Secondary hyperparathyroidism
Chronic kidney disease CKD
Intact parathyroid hormone iPTH
Hemodialysis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-09-14
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).
Primary purpose: TREATMENT

Brief summary: This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3 times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of approximately 4 weeks.

Doses were given at the end of each scheduled hemodialysis session on study days 1 through day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.


Eligibility criteria: Inclusion Criteria:

* Subject has provided informed consent prior to initiation of any study-specific activities/procedures
* Resident in Mainland China and of Chinese ancestry
* Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end stage renal disease receiving hemodialysis
* Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to screening. The subject's routine hemodialysis session must be of 3-4.5 hours in duration, inclusive
* Subject has stable dialysis prescription and this prescription is not anticipated to significantly change during the course of the study

Exclusion Criteria:

* Corrected calcium (calculated) level is \< 2.07 mmol/L (8.3 mg/dL), and/or intact PTH level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL)
* Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or breastfeed while on study through 3 months after receiving the dose of study drug
* Female subject of reproductive potential not willing to use a(n) acceptable method(s) of effective birth control during treatment with AMG 416, and for an additional 3 months after the end of treatment with AMG 416. Female subjects who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation, or who are postmenopausal are not required to use contraception. Postmenopausal is defined as:

  * Age \> 55 years with cessation of menses for 12 months or more
  * Age \< 55 but no spontaneous menses for at least 2 years
  * Age \< 55 years and spontaneous menses within the past 1 years, but currently amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\<5.3 pmol/L or 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved
  * Underwent a bilateral oophorectomy
* Females of reproductive potential with a positive pregnancy test, unless medical follow-up confirms the subject is not pregnant
* Previous administration of AMG 416
* Subject has received cinacalcet within the 30 days prior to informed consent (treatment with cinacalcet is prohibited during the study)
* Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug administration or during the study period
* Anticipated or scheduled to have major surgical procedures during the study period such as kidney transplant or parathyroidectomy
* History of malignancy within 5 years before Day -2 (except non melanoma skin cancers, or cervical carcinoma in situ)
* Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion
* Subject has current or history of cardiovascular conditions such as uncontrolled hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina pectoris congestive heart failure (New York Heart Association Classification III or IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
timeFrame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
measure: PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
timeFrame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
measure: Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
timeFrame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
measure: Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
timeFrame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
Secondary outcomes:
measure: Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 55 (end of study)
measure: Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
timeFrame: Day 1 up to Day 55 (end of study)
measure: Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
timeFrame: Baseline is Day -2; End of Study is Day 55
measure: Change From Baseline to End of Study in Weight
timeFrame: Day 1 up to Day 55
measure: Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
timeFrame: Baseline Day 1 prior to dialysis; End of Study is Day 55
measure: Baseline and Change From Baseline to End of Study in Heart Rate
timeFrame: Baseline Day 1 prior to dialysis; End of Study is Day 55
measure: Change From Baseline to End of Study in Calcium
timeFrame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
measure: Change From Baseline to End of Study in Corrected Calcium (cCa)
timeFrame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
measure: Participants With Low Corrected Calcium (cCA) By Category
timeFrame: Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
measure: Baseline and Change From Baseline to End of Study in Serum Albumin
timeFrame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
measure: Change From Baseline to End of Study in Serum Phosphorus
timeFrame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
measure: Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
timeFrame: Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Xing C, Chen J, Zuo L, Fang Y, Ding X, Ni Z, Kong C, Shi G, Lu H, Hellawell J, Cheng S, Sohn W. A Phase I, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Etelcalcetide Administered Intravenously to Chinese Patients With Chronic Kidney Disease Undergoing Hemodialysis. Clin Ther. 2021 Nov;43(11):2013-2023. doi: 10.1016/j.clinthera.2021.09.019. Epub 2021 Nov 11.