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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Romosozumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Stage 4 Renal Impairment<br>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<br>* Administered as three 70 mg/mL prefilled syringe injections<br>* Other names: EVENITY™;|
| Experimental: Group 2: ESRD Requiring Hemodialysis<br>Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1. | Drug: Romosozumab<br>* Administered as three 70 mg/mL prefilled syringe injections<br>* Other names: EVENITY™;|
| Experimental: Group 3: Healthy Participants<br>Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. | Drug: Romosozumab<br>* Administered as three 70 mg/mL prefilled syringe injections<br>* Other names: EVENITY™;|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment