Back to resultsA First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women
Primary Purpose
Osteopenia
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Romosozumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteopenia focused on measuring Amgen, First in Human, Postmenopausal, Phase 1
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Known sensitivity to mammalian-derived drug preparations
- Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
- Any organic or psychiatric disorder which may pose a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
- Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures
- Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent
- Has a history of drug or alcohol abuse with the last 12 months and/or a positive urine test result at screening or admission
- Has any clinically significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation
- Has participated in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known
- Weight ≥ 98 kilograms (216 pounds) and/or height ≥ 78 inches
- Has donated or lost 400 milliliters or more of blood or plasma within 8 weeks of study drug administration
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Romosozumab
Arm Description
Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.
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.
Outcomes
Primary Outcome Measures
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?'
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.
Secondary Outcome Measures
Maximum Observed Concentration (Cmax) of Romosozumab
Time to Maximum Observed Concentration (Tmax) of Romosozumab
Initial Concentration Following IV Administration (C0) of Romosozumab
Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab
Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab
Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab
The plateau (beta, β) phase half-life (t½,β) was calculated from the natural log of 2 divided by the beta phase rate constant (λβ). λβ for a subject was estimated by linear regression of at least 3 contiguous time points that followed the Cmax and constituted a distinct phase that preceded the terminal phase.
Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab
The terminal (gamma, γ) phase half-life (t½,γ) was calculated from the natural log of 2 divided by the terminal rate constant (λz).
Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)
Defined as the maximum value postdose.
Time to Maximum Effect of P1NP
Defined as the time to maximum value postdose.
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP
Maximum Effect for Serum C-telopeptide (sCTX)
Defined as the minimum value postdose.
Time to Maximum Effect of sCTX
Defined as the time to minimum value postdose.
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX
Maximum Effect for Osteocalcin
Defined as the maximum value postdose.
Time to Maximum Effect of Osteocalcin
Defined as the time to maximum value postdose.
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin
Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP)
Defined as the maximum value postdose.
Time to Maximum Effect of BSAP
Defined as the time to maximum value postdose.
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP
Maximum Effect for Intact Parathyroid Hormone (iPTH)
Defined as the maximum value postdose.
Time to Maximum Effect of iPTH
Defined as the time to maximum value postdose.
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH
Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH
Percent Change From Baseline in Sclerostin
Serum Calcium Over Time
Ionized Calcium Over Time
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01059435
Brief Title
A First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women
Official Title
A Randomized, Double-blind, Placebo-controlled, Ascending Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
December 13, 2006 (Actual)
Primary Completion Date
July 6, 2007 (Actual)
Study Completion Date
July 6, 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteopenia
Keywords
Amgen, First in Human, Postmenopausal, Phase 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.
Arm Title
Romosozumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Romosozumab
Other Intervention Name(s)
AMG 785, EVENITY™
Intervention Description
Administered subcutaneously or intravenously
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered subcutaneously or intravenously
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
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?'
Time Frame
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.
Title
Number of Participants Who Developed Anti-romosozumab Antibodies
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Maximum Observed Concentration (Cmax) of Romosozumab
Time Frame
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.
Title
Time to Maximum Observed Concentration (Tmax) of Romosozumab
Time Frame
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.
Title
Initial Concentration Following IV Administration (C0) of Romosozumab
Time Frame
Day 1 at the end of infusion
Title
Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab
Time Frame
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.
Title
Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab
Time Frame
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.
Title
Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab
Description
The plateau (beta, β) phase half-life (t½,β) was calculated from the natural log of 2 divided by the beta phase rate constant (λβ). λβ for a subject was estimated by linear regression of at least 3 contiguous time points that followed the Cmax and constituted a distinct phase that preceded the terminal phase.
Time Frame
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.
Title
Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab
Description
The terminal (gamma, γ) phase half-life (t½,γ) was calculated from the natural log of 2 divided by the terminal rate constant (λz).
Time Frame
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.
Title
Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)
Description
Defined as the maximum value postdose.
Time Frame
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.
Title
Time to Maximum Effect of P1NP
Description
Defined as the time to maximum value postdose.
Time Frame
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.
Title
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP
Time Frame
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.
Title
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP
Time Frame
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,
Title
Maximum Effect for Serum C-telopeptide (sCTX)
Description
Defined as the minimum value postdose.
Time Frame
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.
Title
Time to Maximum Effect of sCTX
Description
Defined as the time to minimum value postdose.
Time Frame
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.
Title
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX
Time Frame
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.
Title
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX
Time Frame
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.
Title
Maximum Effect for Osteocalcin
Description
Defined as the maximum value postdose.
Time Frame
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.
Title
Time to Maximum Effect of Osteocalcin
Description
Defined as the time to maximum value postdose.
Time Frame
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.
Title
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin
Time Frame
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.
Title
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin
Time Frame
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.
Title
Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP)
Description
Defined as the maximum value postdose.
Time Frame
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.
Title
Time to Maximum Effect of BSAP
Description
Defined as the time to maximum value postdose.
Time Frame
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.
Title
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP
Time Frame
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.
Title
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP
Time Frame
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.
Title
Maximum Effect for Intact Parathyroid Hormone (iPTH)
Description
Defined as the maximum value postdose.
Time Frame
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.
Title
Time to Maximum Effect of iPTH
Description
Defined as the time to maximum value postdose.
Time Frame
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.
Title
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH
Time Frame
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.
Title
Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH
Time Frame
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.
Title
Percent Change From Baseline in Sclerostin
Time Frame
Baseline and days 15, 29, 43, 57, 71, and 85
Title
Serum Calcium Over Time
Time Frame
Dday 1 predose and at 4, 6, 8, 10, and 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
Title
Ionized Calcium Over Time
Time Frame
Day 1 predose and at 4, 6, 8, 10, 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Known sensitivity to mammalian-derived drug preparations
Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
Any organic or psychiatric disorder which may pose a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures
Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent
Has a history of drug or alcohol abuse with the last 12 months and/or a positive urine test result at screening or admission
Has any clinically significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation
Has participated in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known
Weight ≥ 98 kilograms (216 pounds) and/or height ≥ 78 inches
Has donated or lost 400 milliliters or more of blood or plasma within 8 weeks of study drug administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
20593411
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
A First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women
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