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

NCT01833754 | Completed Phase 1 Results

• 1 other identifier: 20110227
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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.

Conditions

Osteoporosis

Keywords

Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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

Study Arms (3)

Group 1: Stage 4 Renal Impairment

EXPERIMENTAL

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

Group 2: ESRD Requiring Hemodialysis

EXPERIMENTAL

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

Drug: Romosozumab

Group 3: Healthy Participants

EXPERIMENTAL

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

Drug: Romosozumab

Interventions

Romosozumab DRUG

Administered as three 70 mg/mL prefilled syringe injections

Also known as: AMG 785, EVENITY™

Group 1: Stage 4 Renal Impairment; Group 2: ESRD Requiring Hemodialysis; Group 3: Healthy Participants

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

Research Site

Tempe, Arizona, 85284, United States

Location

Research Site

Los Angeles, California, 90022, United States

Location

Research Site

Denver, Colorado, 80230, United States

Location

Research Site

Pembroke Pines, Florida, 33028, United States

Location

Research Site

Orangeburg, South Carolina, 29118, United States

Location

Related 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 Sep;62(9):1132-1141. doi: 10.1002/jcph.2050. Epub 2022 Apr 2.

  PMID: 35304747 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis

Interventions

romosozumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 17, 2013
• Study Start: April 22, 2013
• Primary Completion: February 19, 2014
• Study Completion: February 19, 2014
• Last Updated: July 22, 2022
• Results First Posted: February 25, 2019

Record last verified: 2022-07

Locations

US (5)