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

Primary Purpose

Osteoporosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Romosozumab
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1: Stage 4 Renal Impairment

Group 2: ESRD Requiring Hemodialysis

Group 3: Healthy Participants

Arm Description

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.

Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.

Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Outcomes

Primary Outcome Measures

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?"
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.
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.
Intact Parathyroid Hormone (iPTH)Concentrations by Visit

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of Romosozumab
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)

Full Information

First Posted
April 15, 2013
Last Updated
July 15, 2022
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT01833754
Brief Title
Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
April 22, 2013 (Actual)
Primary Completion Date
February 19, 2014 (Actual)
Study Completion Date
February 19, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
Keywords
Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Stage 4 Renal Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2: ESRD Requiring Hemodialysis
Arm Type
Experimental
Arm Description
Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
Arm Title
Group 3: Healthy Participants
Arm Type
Experimental
Arm Description
Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Intervention Type
Drug
Intervention Name(s)
Romosozumab
Other Intervention Name(s)
AMG 785, EVENITY™
Intervention Description
Administered as three 70 mg/mL prefilled syringe injections
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
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?"
Time Frame
From the first dose of study drug up to day 85
Title
Number of Participants Who Developed Anti-Romosozumab Antibodies
Description
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.
Time Frame
Baseline and day 85
Title
Albumin-Adjusted Serum Calcium Concentrations by Visit
Description
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.
Time Frame
Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Title
Intact Parathyroid Hormone (iPTH)Concentrations by Visit
Time Frame
Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of Romosozumab
Time Frame
Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Title
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
Time Frame
Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Title
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Time Frame
Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Title
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time Frame
Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Research Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Research Site
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Research Site
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35304747
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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