A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)
- Registration Number
- NCT01825785
- Lead Sponsor
- Amgen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. Romosozumab Romosozumab 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.
- Primary Outcome Measures
Name Time Method Number of Participants Who Developed Antibodies to Romosozumab 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. 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.Number of Participants With Adverse Events 169 days 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?'
- Secondary Outcome Measures
Name Time Method Maximum Observed Concentration (Cmax) of Romosozumab 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. Percent Change From Baseline in Bone Mineral Density of the Total Spine Baseline and days 29, 85, 127, and 169 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 Femoral Hip Baseline and days 29, 85, 127, and 169 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 Baseline and days 29, 85, 127, and 169 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) 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 Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab 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. 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)
Accumulation Ratio (AR) for Romosozumab 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. 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 Osteocalcin 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 Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) 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 Percent Change From Baseline in Serum C-telopeptide (sCTX) 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 Change From Baseline in Ionized Calcium Baseline and day 169 (or earlier for participants who discontinued before day 169) Time to Maximum Observed Concentration (Tmax) of Romosozumab 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. Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.
Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169. Percent Change From Baseline in Bone Mineral Density at the Total Hip Baseline and days 29, 85, 127, and 169 Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) 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 Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius Baseline and days 29, 85, 127, and 169 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 Baseline and days 29, 85, 127, and 169 Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Percent Change From Baseline in Sclerostin Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169