A First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women

NCT01059435 | Completed Phase 1 Results

• 1 other identifier: 20060220
• Study Type: interventional
• Target: 74
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to assess the safety and tolerability of romosozumab following single dose subcutaneous (SC) or intravenous (IV) administration in healthy men and postmenopausal women.

Conditions

Osteopenia

Keywords

Amgen; First in Human; Postmenopausal; Phase 1

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  Serious adverse events were any events that were fatal, were life-threatening (placed the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, were congenital anomalies or birth defects, or were other significant medical hazards. Relatedness to investigational product was assessed by the investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?'

  Adverse events were collected from the first dose of treatment up until day 29 for the 0.1 mg/kg and 0.3 mg/kg SC treatment groups, up to 57 days for the 1 mg/kg and 3 mg/kg IV/SC groups and for up to 85 days for the 5 mg/kg and 10 mg/kg SC/IV groups.

• Number of Participants Who Developed Anti-romosozumab Antibodies

  Binding anti-romosozumab antibody titers were assessed using a validated electrochemiluninescence (ECL) immunoassay. The limit of detection for this assay was 3.91 ng/mL of anti-romosozumab antibody in neat serum. Samples found to be positive for binding antibodies were further tested using a validated bioassay to determine if the antibodies were able to neutralize the activity of romosozumab. The limit of detection for this assay was ≥ 0.75 μg/mL.

  Day 29 (all participants), day 57 (1, 3, 5, and 10 mg/kg treatment groups only) and at day 85 (5 and 10 mg/kg teatment groups only).

Secondary Outcomes (30)

• Maximum Observed Concentration (Cmax) of Romosozumab

  Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

• Time to Maximum Observed Concentration (Tmax) of Romosozumab

  Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

• Initial Concentration Following IV Administration (C0) of Romosozumab

  Day 1 at the end of infusion

• Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab

  Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

• Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab

  Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.

Drug: Placebo

Romosozumab

EXPERIMENTAL

Participants were randomized to receive a single dose of romosozumab administered by subcutaneous or intravenous injection. The starting dose was 0.1 mg/kg, with sequential escalation up to 10 mg/kg.

Drug: Romosozumab

Interventions

Romosozumab DRUG

Administered subcutaneously or intravenously

Also known as: AMG 785, EVENITY™

Romosozumab

Placebo DRUG

Administered subcutaneously or intravenously

Placebo

Eligibility Criteria

• Age: 45 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or female between 45 to 59 years of age, inclusive
• Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result \> 40mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy)
• Males must agree to use a condom during sexual intercourse with female partners who are of reproductive potential and to have their female partners use an additional effective means of contraception or to abstain from sexual intercourse for the duration of the study
• Has no history or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

You may not qualify if:

• Diagnosed with any condition that will affect bone metabolism
• Administration of the following medications within 6 months before study drug administration:
• Hormone replacement therapy \[Infrequent use of estrogen vaginal creams (\< 3 times per week) is allowed.\]
• Calcitonin
• Parathyroid hormone (or any derivative)
• Supplemental Vitamin D \> 1,000 IU/day
• Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)
• Anabolic steroids
• Calcitriol, and available analogues
• Administration of the following medications within 12 months before study drug administration:
• Bisphosphonates
• Fluoride for osteoporosis
• Administration of herbal medications within 2 weeks or 5 half-lives (whichever is longer) before study drug administration
• Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration
• Routine alcohol intake of \> 2 drinks per day, on average, within 6 months of study drug administration

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011 Jan;26(1):19-26. doi: 10.1002/jbmr.173.

  PMID: 20593411 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Bone Diseases, Metabolic

Interventions

romosozumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: December 13, 2006
• Primary Completion: July 6, 2007
• Study Completion: July 6, 2007
• Last Updated: July 5, 2019
• Results First Posted: July 5, 2019

Record last verified: 2019-07