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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01833754
• Other study ID #: 20110227
• Status: Completed
• Phase: Phase 1
• Start date: April 22, 2013
• Est. completion date: February 19, 2014

Study information

• Verified date: July 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 19, 2014
• Est. primary completion date: February 19, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Renal Insufficiency

Intervention

Drug:
• Romosozumab
Administered as three 70 mg/mL prefilled syringe injections

Locations

Country	Name	City	State
United States	Research Site	Denver	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Mar 19. doi: 10.1002/jcph.2050. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Intact Parathyroid Hormone (iPTH)Concentrations by Visit		Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   AmgenTrials clinical trials website