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Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis

Primary Purpose

Postmenopausal Women With Osteoporosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GP2411
EU-Prolia (EU-authorized Prolia®)
Sponsored by
Sandoz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postmenopausal Women With Osteoporosis focused on measuring Prolia, GP2411, denosumab, postmenopausal osteoporosis

Eligibility Criteria

55 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Postmenopausal women, diagnosed with osteoporosis
  • Aged ≥ 55 and ≤ 80 years at screening
  • Body weight ≥ 50 kg and ≤ 90 kg at screening
  • Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine as measured by DXA
  • At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA

Exclusion Criteria:

  • Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab)
  • History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture
  • History and/or presence of bone metastases, bone disease or metabolic disease
  • Ongoing use of any osteoporosis treatment or use of prohibited treatment
  • Other bone active drugs
  • History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia

Other Inclusion/exclusion criteria may apply

Sites / Locations

  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GP2411

EU authorized Prolia

Arm Description

60 mg /mL subcutaneous injection every 6 months

60 mg /mL subcutaneous injection every 6 months

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set
Bone density measurements were performed by dual energy X-ray absorptiometry (DXA). Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Values at Week 52 were estimated from the model and are presented in the table.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A MMRM was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Missing values were assumed to be missing at random (MAR) using the MMRM model. Values at Week 52 were estimated from the model and are presented in the table.
Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set
Carboxy-terminal crosslinked telopeptides of type I collagen (CTX) is a bone resorption biomarker. Serum CTX concentration-time data were analyzed by non-compartmental methods. The AUEC of baseline corrected serum CTX concentrations (% change from baseline) was calculated using the linear trapezoidal method. Values below the lower limit of quantification (LLOQ) were imputed with the actual value for the LLOQ.
Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose
Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero.
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose
Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero. The linear-up log-down trapezoidal method was used for the AUCinf calculation.

Secondary Outcome Measures

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set)
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set)
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Bone density measurement were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (TP1 Full Analysis Set)
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (TP1 Full Analysis Set)
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study.
CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
CTX is a bone resorption biomarker. Serum samples were analyzed for CTX concentrations. CTX serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
CTX is a bone resorption biomarker. Serum samples were analyzed for CTX concentrations. CTX serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Procollagen I N-terminal propeptide (PINP) is a bone formation biomarker. Serum samples were analyzed for PINP concentrations. PINP serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
PINP is a bone formation biomarker. Serum samples were analyzed for PINP concentrations. PINP serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1
Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during Treatment Period 1. The number of participants in each category is reported in the table.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2
Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during Treatment Period 2. The number of participants in each category is reported in the table.
Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1
Vertebral fractures were assessed by independent radiologists at the central imaging vendor. The radiologists assessed lateral thoracic (vertebrae T4 to T12) and lumbar (vertebrae L1 to L4) spine radiographs for vertebral fractures. New and worsening vertebral fractures are defined as occurrence of new fracture (i.e. change in Genant score from 0 at baseline to 1 or higher at a later time point) or worsening fracture (i.e. increase in Genant score from baseline at a later time point) in any assessed vertebra. The Genant classification of vertebral fractures is based on the vertebral shape, with respect to vertebral height loss involving the anterior, posterior, and/or middle vertebral body and ranges between 0 (normal) and 3 (severe fracture, >40% loss of height). The number of participants in each category is reported in the table.
Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Vertebral fractures were assessed by independent radiologists at the central imaging vendor. The radiologists assessed lateral thoracic (vertebrae T4 to T12) and lumbar (vertebrae L1 to L4) spine radiographs for vertebral fractures. New and worsening vertebral fractures are defined as occurrence of new fracture (i.e. change in Genant score from 0 at Week 52 to 1 or higher at a later time point) or worsening fracture (i.e. increase in Genant score from Week 52 at a later time point) in any assessed vertebra. The Genant classification of vertebral fractures is based on the vertebral shape, with respect to vertebral height loss involving the anterior, posterior, and/or middle vertebral body and ranges between 0 (normal) and 3 (severe fracture, >40% loss of height). The number of participants in each category is reported in the table.
Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1
Information about any nonvertebral fractures while on study were recorded as adverse events. The diagnosis of nonvertebral fractures did not require central X-ray reading and was based on local radiology reports. The number of participants in each category is reported in the table.
Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Information about any nonvertebral fractures while on study were recorded as adverse events. The diagnosis of nonvertebral fractures did not require central X-ray reading and was based on local radiology reports. The number of participants in each category is reported in the table.
Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1
The injection site reaction (ISR) assessment was done by the investigator/designee. It consisted of grading the severity of each injection reaction based on criteria the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The ISR grading was defined as follows: Grade 1: Tenderness with or without associated symptoms (e.g., warmth, erythema, itching) Grade 2: Pain; lipodystrophy; edema; phlebitis Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4: Life-threatening consequences; urgent intervention indicated The number of participants in each category is reported in the table.
Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2
The injection site reaction (ISR) assessment was done by the investigator/designee. It consisted of grading the severity of each injection reaction based on criteria the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The ISR grading was defined as follows: Grade 1: Tenderness with or without associated symptoms (e.g., warmth, erythema, itching) Grade 2: Pain; lipodystrophy; edema; phlebitis Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4: Life-threatening consequences; urgent intervention indicated The number of participants in each category is reported in the table.
Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1
Immunogenicity was evaluated in serum. Samples were screened for potential anti-drug antibodies (ADA) and positive screen results were confirmed using a confirmatory assay. For confirmed ADA positive samples, titers were determined. Confirmed ADAs were also analyzed for their neutralization potential. Patient ADA status was defined as follows: ADA Positive: ADA-positive sample at any time point during TP1 ADA Positive, Persistent: 'Persistent' indicates a subject experiencing a positive ADA result at the final visit and with at least 2 consecutive positive ADA results ADA Positive, Transient: 'Transient' indicates a subject experiencing positive ADA result but not qualifying as 'Persistent' ADA titer positive: ADA-positive sample with a titer result ≥ 20 ng/mL NAb Positive: ADA-positive sample with presence of neutralizing antibodies (NAb) The number of participants in each category is reported in the table.
Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2
Immunogenicity was evaluated in serum. Samples were screened for potential anti-drug antibodies (ADA) and positive screen results were confirmed using a confirmatory assay. For confirmed ADA positive samples, titers were determined. Confirmed ADAs were also analyzed for their neutralization potential. Patient ADA status was defined as follows: ADA Positive: ADA-positive sample at any time point during TP1 ADA Positive, Persistent: 'Persistent' indicates a subject experiencing a positive ADA result at the final visit and with at least 2 consecutive positive ADA results ADA Positive, Transient: 'Transient' indicates a subject experiencing positive ADA result but not qualifying as 'Persistent' ADA titer positive: ADA-positive sample with a titer result ≥ 20 ng/mL NAb Positive: ADA-positive sample with presence of neutralizing antibodies (NAb) The number of participants in each category is reported in the table.
Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Serum samples were analyzed for concentrations of free denosumab by using a validated ligand binding assay. Briefly, the concentration of free denosumab was determined by binding to coated ligand molecules. Denosumab concentrations below the LLOQ were set to zero in order to calculate arithmetic means.
Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Serum samples were analyzed for concentrations of free denosumab by using a validated ligand binding assay. Briefly, the concentration of free denosumab was determined by binding to coated ligand molecules. Denosumab concentrations below the LLOQ were set to zero in order to calculate arithmetic means.

Full Information

First Posted
June 3, 2019
Last Updated
February 7, 2023
Sponsor
Sandoz
Collaborators
Hexal AG
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1. Study Identification

Unique Protocol Identification Number
NCT03974100
Brief Title
Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis
Official Title
A Randomized, Double-blind, Multicenter Integrated Phase I/III Study in Postmenopausal Women With Osteoporosis to Compare the Pharmacokinetics, Pharmacodynamics, Efficacy, Safety and Immunogenicity of GP2411 (Proposed Biosimilar Denosumab) and Prolia® (EU-authorized)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
July 2, 2019 (Actual)
Primary Completion Date
April 22, 2022 (Actual)
Study Completion Date
April 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sandoz
Collaborators
Hexal AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study was conducted to assess if there were any clinically meaningful differences in pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety, or immunogenicity between GP2411 (proposed biosimilar denosumab) and EU-authorized Prolia® (denosumab).
Detailed Description
This was an international, multicenter, randomized, double-blind, parallel-group study with a total duration of up to 83 weeks. The study comprised a screening period of up to 5 weeks to assess a subject's eligibility and two treatment periods: Treatment Period 1 (TP1) from Day 1 to Week 52 and Treatment Period 2 (TP2) from Week 52 to Week 78. Women with postmenopausal osteoporosis (PMO) were randomized on Day 1 in a 1:1 ratio to receive either two 60 mg subcutaneous (s.c.) doses at 26-week intervals of GP2411 (proposed biosimilar denosumab) or EU-Prolia (EU-authorized Prolia®) during TP1. At Week 52, participants in the EU-Prolia group were re-randomized 1:1 to either continue with a third dose of EU-Prolia or switch to GP2411 for TP2. Participants in the GP2411 group continued the treatment with a third dose of GP2411 in TP2. The End of Study was achieved at Week 78.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Women With Osteoporosis
Keywords
Prolia, GP2411, denosumab, postmenopausal osteoporosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
double blind
Allocation
Randomized
Enrollment
527 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GP2411
Arm Type
Experimental
Arm Description
60 mg /mL subcutaneous injection every 6 months
Arm Title
EU authorized Prolia
Arm Type
Active Comparator
Arm Description
60 mg /mL subcutaneous injection every 6 months
Intervention Type
Biological
Intervention Name(s)
GP2411
Intervention Description
60 mg /mL subcutaneous injection every 6 months
Intervention Type
Biological
Intervention Name(s)
EU-Prolia (EU-authorized Prolia®)
Intervention Description
60 mg /mL subcutaneous injection every 6 months
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set
Description
Bone density measurements were performed by dual energy X-ray absorptiometry (DXA). Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Values at Week 52 were estimated from the model and are presented in the table.
Time Frame
Baseline (screening), up to Week 52
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set
Description
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A MMRM was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Missing values were assumed to be missing at random (MAR) using the MMRM model. Values at Week 52 were estimated from the model and are presented in the table.
Time Frame
Baseline (screening), up to Week 52
Title
Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set
Description
Carboxy-terminal crosslinked telopeptides of type I collagen (CTX) is a bone resorption biomarker. Serum CTX concentration-time data were analyzed by non-compartmental methods. The AUEC of baseline corrected serum CTX concentrations (% change from baseline) was calculated using the linear trapezoidal method. Values below the lower limit of quantification (LLOQ) were imputed with the actual value for the LLOQ.
Time Frame
Baseline (pre-dose Day 1), up to Week 26
Title
Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose
Description
Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero.
Time Frame
Baseline (pre-dose Day 1), up to Week 26
Title
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose
Description
Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero. The linear-up log-down trapezoidal method was used for the AUCinf calculation.
Time Frame
Baseline (pre-dose Day 1), up to Week 26
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set)
Description
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set)
Description
Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Description
Bone density measurement were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 78
Title
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Description
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26 and Week 52
Title
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (TP1 Full Analysis Set)
Description
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26 and Week 52
Title
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Description
Bone density measurements were performed by DXA. For proximal femur, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 78
Title
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Description
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26 and Week 52
Title
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (TP1 Full Analysis Set)
Description
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study. All DXA scans were submitted to a central imaging vendor for analysis.
Time Frame
Baseline (screening), Week 26 and Week 52
Title
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Description
Bone density measurements were performed by DXA. For total hip, the left side was to be used for all DXA scans at all study visits. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it was to be used consistently throughout the study.
Time Frame
Baseline (screening), Week 78
Title
CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Description
CTX is a bone resorption biomarker. Serum samples were analyzed for CTX concentrations. CTX serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
Time Frame
Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
Title
CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Description
CTX is a bone resorption biomarker. Serum samples were analyzed for CTX concentrations. CTX serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
Time Frame
Week 56, Week 65 and Week 78
Title
PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Description
Procollagen I N-terminal propeptide (PINP) is a bone formation biomarker. Serum samples were analyzed for PINP concentrations. PINP serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
Time Frame
Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
Title
PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Description
PINP is a bone formation biomarker. Serum samples were analyzed for PINP concentrations. PINP serum concentrations were determined by a validated ligand-binding immunoassay. Values below the LLOQ were imputed with the actual value for the LLOQ.
Time Frame
Week 56, Week 65 and Week 78
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1
Description
Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during Treatment Period 1. The number of participants in each category is reported in the table.
Time Frame
From first dose of study treatment on Day 1 up to pre-dose at Week 52
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2
Description
Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during Treatment Period 2. The number of participants in each category is reported in the table.
Time Frame
From dosing of study treatment at Week 52 up to Week 78
Title
Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1
Description
Vertebral fractures were assessed by independent radiologists at the central imaging vendor. The radiologists assessed lateral thoracic (vertebrae T4 to T12) and lumbar (vertebrae L1 to L4) spine radiographs for vertebral fractures. New and worsening vertebral fractures are defined as occurrence of new fracture (i.e. change in Genant score from 0 at baseline to 1 or higher at a later time point) or worsening fracture (i.e. increase in Genant score from baseline at a later time point) in any assessed vertebra. The Genant classification of vertebral fractures is based on the vertebral shape, with respect to vertebral height loss involving the anterior, posterior, and/or middle vertebral body and ranges between 0 (normal) and 3 (severe fracture, >40% loss of height). The number of participants in each category is reported in the table.
Time Frame
Baseline (screening) and Week 52
Title
Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Description
Vertebral fractures were assessed by independent radiologists at the central imaging vendor. The radiologists assessed lateral thoracic (vertebrae T4 to T12) and lumbar (vertebrae L1 to L4) spine radiographs for vertebral fractures. New and worsening vertebral fractures are defined as occurrence of new fracture (i.e. change in Genant score from 0 at Week 52 to 1 or higher at a later time point) or worsening fracture (i.e. increase in Genant score from Week 52 at a later time point) in any assessed vertebra. The Genant classification of vertebral fractures is based on the vertebral shape, with respect to vertebral height loss involving the anterior, posterior, and/or middle vertebral body and ranges between 0 (normal) and 3 (severe fracture, >40% loss of height). The number of participants in each category is reported in the table.
Time Frame
Week 52 and Week 78
Title
Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1
Description
Information about any nonvertebral fractures while on study were recorded as adverse events. The diagnosis of nonvertebral fractures did not require central X-ray reading and was based on local radiology reports. The number of participants in each category is reported in the table.
Time Frame
From first dose of study treatment on Day 1 up to pre-dose at Week 52
Title
Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Description
Information about any nonvertebral fractures while on study were recorded as adverse events. The diagnosis of nonvertebral fractures did not require central X-ray reading and was based on local radiology reports. The number of participants in each category is reported in the table.
Time Frame
From dosing of study treatment at Week 52 up to Week 78
Title
Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1
Description
The injection site reaction (ISR) assessment was done by the investigator/designee. It consisted of grading the severity of each injection reaction based on criteria the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The ISR grading was defined as follows: Grade 1: Tenderness with or without associated symptoms (e.g., warmth, erythema, itching) Grade 2: Pain; lipodystrophy; edema; phlebitis Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4: Life-threatening consequences; urgent intervention indicated The number of participants in each category is reported in the table.
Time Frame
From first dose of study treatment on Day 1 up to pre-dose at Week 52
Title
Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2
Description
The injection site reaction (ISR) assessment was done by the investigator/designee. It consisted of grading the severity of each injection reaction based on criteria the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The ISR grading was defined as follows: Grade 1: Tenderness with or without associated symptoms (e.g., warmth, erythema, itching) Grade 2: Pain; lipodystrophy; edema; phlebitis Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4: Life-threatening consequences; urgent intervention indicated The number of participants in each category is reported in the table.
Time Frame
From dosing of study treatment at Week 52 up to Week 78
Title
Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1
Description
Immunogenicity was evaluated in serum. Samples were screened for potential anti-drug antibodies (ADA) and positive screen results were confirmed using a confirmatory assay. For confirmed ADA positive samples, titers were determined. Confirmed ADAs were also analyzed for their neutralization potential. Patient ADA status was defined as follows: ADA Positive: ADA-positive sample at any time point during TP1 ADA Positive, Persistent: 'Persistent' indicates a subject experiencing a positive ADA result at the final visit and with at least 2 consecutive positive ADA results ADA Positive, Transient: 'Transient' indicates a subject experiencing positive ADA result but not qualifying as 'Persistent' ADA titer positive: ADA-positive sample with a titer result ≥ 20 ng/mL NAb Positive: ADA-positive sample with presence of neutralizing antibodies (NAb) The number of participants in each category is reported in the table.
Time Frame
From Week 2 up to Week 52
Title
Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2
Description
Immunogenicity was evaluated in serum. Samples were screened for potential anti-drug antibodies (ADA) and positive screen results were confirmed using a confirmatory assay. For confirmed ADA positive samples, titers were determined. Confirmed ADAs were also analyzed for their neutralization potential. Patient ADA status was defined as follows: ADA Positive: ADA-positive sample at any time point during TP1 ADA Positive, Persistent: 'Persistent' indicates a subject experiencing a positive ADA result at the final visit and with at least 2 consecutive positive ADA results ADA Positive, Transient: 'Transient' indicates a subject experiencing positive ADA result but not qualifying as 'Persistent' ADA titer positive: ADA-positive sample with a titer result ≥ 20 ng/mL NAb Positive: ADA-positive sample with presence of neutralizing antibodies (NAb) The number of participants in each category is reported in the table.
Time Frame
From Week 56 up to Week 78
Title
Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Description
Serum samples were analyzed for concentrations of free denosumab by using a validated ligand binding assay. Briefly, the concentration of free denosumab was determined by binding to coated ligand molecules. Denosumab concentrations below the LLOQ were set to zero in order to calculate arithmetic means.
Time Frame
Baseline (pre-dose Day 1), Day 4, Week 1, Week 2, Week 8, Week 14, Week 18, Week 22, Week 26, Week 39 and Week 52
Title
Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Description
Serum samples were analyzed for concentrations of free denosumab by using a validated ligand binding assay. Briefly, the concentration of free denosumab was determined by binding to coated ligand molecules. Denosumab concentrations below the LLOQ were set to zero in order to calculate arithmetic means.
Time Frame
Week 56, Week 65 and Week 78

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Postmenopausal women, diagnosed with osteoporosis
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Postmenopausal women, diagnosed with osteoporosis Aged ≥ 55 and ≤ 80 years at screening Body weight ≥ 50 kg and ≤ 90 kg at screening Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine as measured by DXA At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA Exclusion Criteria: Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab) History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture History and/or presence of bone metastases, bone disease or metabolic disease Ongoing use of any osteoporosis treatment or use of prohibited treatment Other bone active drugs History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia
Facility Information:
Facility Name
Sandoz Investigational Site
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
Facility Name
Sandoz Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Sandoz Investigational Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67207
Country
United States
Facility Name
Sandoz Investigational Site
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Sandoz Investigational Site
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Sandoz Investigational Site
City
Carrollton
State/Province
Texas
ZIP/Postal Code
75010
Country
United States
Facility Name
Sandoz Investigational Site
City
Plovdiv
ZIP/Postal Code
4001
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Sofia
ZIP/Postal Code
1505
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Sofia
ZIP/Postal Code
1680
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Sofia
ZIP/Postal Code
1784
Country
Bulgaria
Facility Name
Sandoz Investigational Site
City
Ostrava
State/Province
Czech Republic
ZIP/Postal Code
772 00
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Hradec Kralove
State/Province
CZE
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Brno
ZIP/Postal Code
602 00
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Ostrava
ZIP/Postal Code
702 00
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Pardubice
ZIP/Postal Code
530 02
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Plzen
ZIP/Postal Code
30460
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Praha 11
ZIP/Postal Code
14900
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Praha 2
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Uherske Hradiste
ZIP/Postal Code
686 01
Country
Czechia
Facility Name
Sandoz Investigational Site
City
Fujimi
State/Province
Saitama
ZIP/Postal Code
354-0021
Country
Japan
Facility Name
Sandoz Investigational Site
City
Chuoh-ku
State/Province
Tokyo
ZIP/Postal Code
104-0031
Country
Japan
Facility Name
Sandoz Investigational Site
City
Hachioji-city
State/Province
Tokyo
ZIP/Postal Code
192-0046
Country
Japan
Facility Name
Sandoz Investigational Site
City
Kiyose-city
State/Province
Tokyo
ZIP/Postal Code
204-0021
Country
Japan
Facility Name
Sandoz Investigational Site
City
Shinagawa
State/Province
Tokyo
ZIP/Postal Code
140-0014
Country
Japan
Facility Name
Sandoz Investigational Site
City
Krakow
State/Province
Malopolskie
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Sandoz Investigational Site
City
Bialystok
ZIP/Postal Code
15-351
Country
Poland
Facility Name
Sandoz Investigational Site
City
Bialystok
ZIP/Postal Code
15-461
Country
Poland
Facility Name
Sandoz Investigational Site
City
Bydgoszcz
ZIP/Postal Code
85 168
Country
Poland
Facility Name
Sandoz Investigational Site
City
Lodz
ZIP/Postal Code
90 242
Country
Poland
Facility Name
Sandoz Investigational Site
City
Nadarzyn
ZIP/Postal Code
05-830
Country
Poland
Facility Name
Sandoz Investigational Site
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Sandoz Investigational Site
City
Warszawa
ZIP/Postal Code
00-874
Country
Poland
Facility Name
Sandoz Investigational Site
City
Warszawa
ZIP/Postal Code
02 118
Country
Poland
Facility Name
Sandoz Investigational Site
City
Warszawa
ZIP/Postal Code
02 691
Country
Poland
Facility Name
Sandoz Investigational Site
City
Santiago de Compostela
State/Province
A Coruna
ZIP/Postal Code
15705
Country
Spain
Facility Name
Sandoz Investigational Site
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Sandoz Investigational Site
City
Santiago de Compostela
State/Province
Galicia
ZIP/Postal Code
15706
Country
Spain
Facility Name
Sandoz Investigational Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Sandoz Investigational Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Sandoz Investigational Site
City
Sevilla
ZIP/Postal Code
41010
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Learn more about this trial

Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis

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