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

Phase 1

Completed

• Conditions: Osteopenia
• Interventions: Drug: Placebo; Drug: Romosozumab

• Registration Number: NCT01101061
• Lead Sponsor: Amgen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-04-08
• Study First Submitted QC: 2010-04-08
• Study First Posted: 2010-04-09
• Study Start: 2010-05-03
• Primary Completion: 2010-11-01
• Study Completion: 2010-11-01
• Results First Submitted: 2019-04-10
• Status Verified: 2019-07
• Results First Submitted QC: 2019-07-29
• Last Update Submitted: 2019-07-29
• Results First Posted: 2019-07-31
• Last Update Posted: 2019-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 31

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive a single dose of placebo.
Romosozumab	Romosozumab	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	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.	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.
Number of Participants Who Developed Anti-romosozumab Binding Antibodies	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)	Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.
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

Name	Time	Method
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	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Maximum Observed Concentration of Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Apparent Clearance (CL/F) of Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab	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.	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.