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A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)

Primary Purpose

Postmenopausal, Osteopenia

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Romosozumab
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postmenopausal

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy males and females between 45 to 80 years of age
  • Postmenopausal females
  • Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine [L1-L4] or total evaluable vertebrae [if fewer than L1-L4] or total hip)
  • 25-hydroxyvitamin D ≥ 20 ng/mL
  • Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)

Exclusion Criteria:

  • Osteoporosis defined by bone mineral density (BMD) T-scores < -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip
  • Diagnosed with any condition that would affect bone metabolism
  • Previous exposure to AMG 785

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 matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W) for 3 months.

    Participants were randomized to receive romosozumab administered by subcutaneous injection at doses of 1 mg/kg Q2W, 2 mg/kg Q4W, 2 mg/kg Q2W, or 3 mg/kg Q4W for 3 months.

    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 Antibodies to Romosozumab
    All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing. Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.

    Secondary Outcome Measures

    Time to Maximum Observed Concentration (Tmax) of Romosozumab
    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.
    Maximum Observed Concentration (Cmax) of Romosozumab
    Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab
    Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)
    Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab
    Accumulation Ratio (AR) for Romosozumab
    The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.
    Percent Change From Baseline in Bone Mineral Density of the Total Spine
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.
    Percent Change From Baseline in Bone Mineral Density at the Total Hip
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Percent Change From Baseline in Bone Mineral Density at the Femoral Hip
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Percent Change From Baseline in Bone Mineral Density at the Total Wrist
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Percent Change From Baseline in Bone Mineral Density of the Whole Body
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)
    Percent Change From Baseline in Osteocalcin
    Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
    Percent Change From Baseline in Serum C-telopeptide (sCTX)
    Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
    Percent Change From Baseline in Sclerostin
    Change From Baseline in Ionized Calcium

    Full Information

    First Posted
    January 25, 2013
    Last Updated
    August 28, 2023
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01825785
    Brief Title
    A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)
    Official Title
    A Randomized, Double-blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women With Low Bone Mass
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    November 14, 2007 (Actual)
    Primary Completion Date
    December 2, 2008 (Actual)
    Study Completion Date
    December 2, 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The primary objective of this study was to assess the safety, tolerability, and immunogenicity potential of romosozumab following multiple subcutaneous (SC) administrations in healthy men and postmenopausal women with low bone mass.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Postmenopausal, Osteopenia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    48 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W) for 3 months.
    Arm Title
    Romosozumab
    Arm Type
    Experimental
    Arm Description
    Participants were randomized to receive romosozumab administered by subcutaneous injection at doses of 1 mg/kg Q2W, 2 mg/kg Q4W, 2 mg/kg Q2W, or 3 mg/kg Q4W for 3 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Romosozumab
    Other Intervention Name(s)
    AMG 785, EVENITY™
    Intervention Description
    Administered by subcutaneous injection
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Administered by subcutaneous injection
    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
    169 days
    Title
    Number of Participants Who Developed Antibodies to Romosozumab
    Description
    All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing. Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.
    Time Frame
    Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.
    Secondary Outcome Measure Information:
    Title
    Time to Maximum Observed Concentration (Tmax) of Romosozumab
    Description
    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.
    Time Frame
    Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
    Title
    Maximum Observed Concentration (Cmax) of Romosozumab
    Time Frame
    Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
    Title
    Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab
    Description
    Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)
    Time Frame
    Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
    Title
    Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab
    Time Frame
    Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.
    Title
    Accumulation Ratio (AR) for Romosozumab
    Description
    The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.
    Time Frame
    Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
    Title
    Percent Change From Baseline in Bone Mineral Density of the Total Spine
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Bone Mineral Density at the Total Hip
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Bone Mineral Density at the Femoral Hip
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Bone Mineral Density at the Total Wrist
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Bone Mineral Density of the Whole Body
    Description
    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
    Time Frame
    Baseline and days 29, 85, 127, and 169
    Title
    Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)
    Time Frame
    Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
    Title
    Percent Change From Baseline in Osteocalcin
    Time Frame
    Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
    Title
    Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
    Time Frame
    Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
    Title
    Percent Change From Baseline in Serum C-telopeptide (sCTX)
    Time Frame
    Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
    Title
    Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
    Time Frame
    Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
    Title
    Percent Change From Baseline in Sclerostin
    Time Frame
    Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169
    Title
    Change From Baseline in Ionized Calcium
    Time Frame
    Baseline and day 169 (or earlier for participants who discontinued before day 169)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    45 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Healthy males and females between 45 to 80 years of age Postmenopausal females Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine [L1-L4] or total evaluable vertebrae [if fewer than L1-L4] or total hip) 25-hydroxyvitamin D ≥ 20 ng/mL Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in) Exclusion Criteria: Osteoporosis defined by bone mineral density (BMD) T-scores < -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip Diagnosed with any condition that would affect bone metabolism Previous exposure to AMG 785
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

    A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)

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