Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis

A Phase 1, Open-label, Single-dose Study of Romosozumab (AMG 785) Administered Subcutaneously to Healthy Subjects and Subjects With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Romosozumab

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Research Site
  • California
    • Los Angeles, California, United States, 90022
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Research Site
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA - ALL SUBJECTS :

• Males or females ≥ 50 years of age
• Body weight ≥ 45 and ≤ 110 kg
• Willing to adhere to calcium and vitamin D supplementation requirements
• Females must be of non-reproductive potential

INCLUSION CRITERIA - SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 AND 2):

• Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²)
• Group 2 - End stage renal disease requiring hemodialysis

INCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3):

• Renal function defined as an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m²

EXCLUSION CRITERIA - ALL SUBJECTS:

• History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects)
• History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50
• Recent bone fracture
• Vitamin D insufficiency
• Hypocalcemia or hypercalcemia
• Hypomagnesemia
• Hypophosphatemia
• Untreated hyper- or hypothyroidism
• Females with a positive pregnancy test
• Males with pregnant partners
• Females who are lactating/breastfeeding or plan to breastfeed on study and for 3 months after receiving the dose of study drug
• History of spinal stenosis
• History of facial nerve paralysis
• Positive for human immunodeficiency virus (HIV) antibodies
• Positive for hepatitis B surface antigen or detectable hepatitis C
• Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical, or breast ductal carcinoma in situ) within 5 years before screening
• History of solid organ or bone marrow transplants EXCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3)
• Current hyper- or hypoparathyroidism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Stage 4 Renal Impairment; Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab; Administered as three 70 mg/mL prefilled syringe injections; Other Names: AMG 785; EVENITY™
Experimental: Group 2: ESRD Requiring Hemodialysis; Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab; Administered as three 70 mg/mL prefilled syringe injections; Other Names: AMG 785; EVENITY™
Experimental: Group 3: Healthy Participants; Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab; Administered as three 70 mg/mL prefilled syringe injections; Other Names: AMG 785; EVENITY™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"	From the first dose of study drug up to day 85
Number of Participants Who Developed Anti-Romosozumab Antibodies	Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.	Baseline and day 85
Albumin-Adjusted Serum Calcium Concentrations by Visit	Albumin-adjusted calcium was derived as: Where serum albumin < 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 * [40 - serum albumin (g/L)]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.	Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Intact Parathyroid Hormone (iPTH)Concentrations by Visit		Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Serum Concentration (Cmax) of Romosozumab	Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab	Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)	Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Hsu CP, Maddox J, Block G, Bartley Y, Yu Z. Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab. J Clin Pharmacol. 2022 Sep;62(9):1132-1141. doi: 10.1002/jcph.2050. Epub 2022 Apr 2.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2013
• Primary Completion (Actual): February 19, 2014
• Study Completion (Actual): February 19, 2014

Study Registration Dates

• First Submitted: April 15, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 17, 2013

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Renal Insufficiency; Osteoporosis
• Other Study ID Numbers: 20110227