A Single-dose Study Evaluating Romosozumab (AMG 785) in Healthy Postmenopausal Japanese and Non-Japanese Women

Study Overview
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Brief Summary
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The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Postmenopausal Japanese Women

Conditions
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Osteopenia

Intervention / Treatment
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* Drug: Romosozumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese subjects must be first (4 grandparents, biologic parents and subject born in Japan), second (4 grandparents and biological parents born in Japan) or third (4 grandparents born in Japan) generation Japanese Body mass index ≤ 25 kg/m², inclusive at screening Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy) as documented in medical history (verified with an operative note, if available) Exclusion Criteria: Osteoporosis, as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck ≤ -2.5 History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis; Diagnosed with any condition that will affect bone metabolism

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab<br>Japanese women in cohorts 1, 2, and 4 will receive a single dose of 1, 3, or 5 mg/kg romosozumab. Non-Japanese women in cohort 3 will receive a single dose of 3 mg/kg romosozumab. | Drug: Romosozumab<br>* Administered by subcutaneous injection<br>* Other names: EVENITY™;|
| Placebo Comparator: Placebo<br>Participants will receive a single dose of placebo. | Drug: Placebo<br>* Administered by subcutaneous injection<br>|

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 (SAE) is defined as an adverse event that is fatal is life threatening requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity is a congenital anomaly/birth defect other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product. | Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments. | 
| Number of Participants Who Developed Anti-romosozumab Binding Antibodies | Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline. | Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo) | 
| Serum Calcium Levels |  | Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | 
| Serum Intact Parathyroid Hormone (iPTH) Levels |  | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) |  | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | 
| Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) |  | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | 
| Percent Change From Baseline in Sclerostin |  | Baseline and days 12, 29, 43, 57, 71, and 85 | 
| Time to Maximum Observed Concentration of Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Maximum Observed Concentration of Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Apparent Clearance (CL/F) of Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 
| Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen, Phase 1, Postmenopausal, Japanese