Postmenopausal Women With Osteoporosis
Conditions
Keywords
Prolia, GP2411, denosumab, postmenopausal osteoporosis
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.
Interventions
BIOLOGICALGP2411
60 mg /mL subcutaneous injection every 6 months
BIOLOGICALEU-Prolia (EU-authorized Prolia®)
60 mg /mL subcutaneous injection every 6 months
Sponsors
Hexal AG
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
double blind
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set | Baseline (screening), up to Week 52 | 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 | Baseline (screening), up to Week 52 | 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 | Baseline (pre-dose Day 1), up to Week 26 | 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 | Baseline (pre-dose Day 1), up to Week 26 | 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 | Baseline (pre-dose Day 1), up to Week 26 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | Baseline (screening), Week 78 | 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) | Baseline (screening), Week 26 and Week 52 | 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) | Baseline (screening), Week 26 and Week 52 | 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) | Baseline (screening), Week 78 | 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 | Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52 | 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 | Week 56, Week 65 and Week 78 | 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 | Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52 | 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 | Week 56, Week 65 and Week 78 | 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 | From first dose of study treatment on Day 1 up to pre-dose at Week 52 | 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 | From dosing of study treatment at Week 52 up to Week 78 | 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. |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set) | Baseline (screening), Week 26 | 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. |
| Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Week 52 and Week 78 | 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 | From first dose of study treatment on Day 1 up to pre-dose at Week 52 | 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 | From dosing of study treatment at Week 52 up to Week 78 | 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 | From first dose of study treatment on Day 1 up to pre-dose at Week 52 | 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 | From dosing of study treatment at Week 52 up to Week 78 | 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 | From Week 2 up to Week 52 | 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 | From Week 56 up to Week 78 | 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 | 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 | 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 | Week 56, Week 65 and Week 78 | 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. |
| Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | Baseline (screening) and Week 52 | 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. |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set) | Baseline (screening), Week 26 | 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) | Baseline (screening), Week 78 | 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) | Baseline (screening), Week 26 and Week 52 | 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) | Baseline (screening), Week 26 and Week 52 | 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. |
Countries
Bulgaria, Czechia, Japan, Poland, Spain, United States
Participant flow
Recruitment details
Participants took part in 43 investigative sites in 6 countries.
Pre-assignment details
The screening period of up to 5 weeks began after the subject had provided written informed consent and ended at the randomization visit (Day 1). On Day 1, participants were randomized in a 1:1 ratio to receive either GP2411 or EU-Prolia during Treatment Period 1 (TP1). At Week 52, participants in the EU-Prolia group were re-randomized 1:1 to either continue with EU-Prolia or switch to GP2411 for Treatment Period 2 (TP2). Participants in the GP2411 group continued with GP2411 for TP2.
Participants by arm
| Arm | Count |
|---|---|
| GP2411 Two 60 mg s.c. doses at 26-week intervals of GP2411 (proposed biosimilar denosumab) in TP1 | 263 |
| EU-Prolia Two 60 mg s.c. doses at 26-week intervals of EU-Prolia (denosumab) in TP1 | 264 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| TP1 - Day 1 to Week 52 | Adverse Event | 1 | 3 | 0 | 0 | 0 |
| TP1 - Day 1 to Week 52 | Death | 1 | 0 | 0 | 0 | 0 |
| TP1 - Day 1 to Week 52 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| TP1 - Day 1 to Week 52 | Physician Decision | 0 | 2 | 0 | 0 | 0 |
| TP1 - Day 1 to Week 52 | Subject decision | 8 | 9 | 0 | 0 | 0 |
| TP2- Week 52 to Week 78 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| TP2- Week 52 to Week 78 | Subject decision | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | GP2411 | EU-Prolia | Total |
|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 6.08 | 64.7 years STANDARD_DEVIATION 5.78 | 64.7 years STANDARD_DEVIATION 5.92 |
| Race/Ethnicity, Customized Asian | 23 Participants | 24 Participants | 47 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 239 Participants | 240 Participants | 479 Participants |
| Sex: Female, Male Female | 263 Participants | 264 Participants | 527 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 263 | 0 / 264 | 0 / 253 | 0 / 125 | 0 / 124 |
| other Total, other adverse events | 89 / 263 | 119 / 264 | 33 / 253 | 29 / 125 | 24 / 124 |
| serious Total, serious adverse events | 12 / 263 | 8 / 264 | 4 / 253 | 2 / 125 | 0 / 124 |
Outcome results
Primary
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.
Time frame: Baseline (pre-dose Day 1), up to Week 26
Population: Pharmacodynamic Analysis Set (PDS) defined as participants who were randomized into TP1 and met the following criteria: CTX values are available in order to be able to calculate AUEC, they received treatment according to protocol on Day 1 and they did not experience relevant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set | 15700 percentage change (%)*day | Geometric Coefficient of Variation 15.8 |
| EU-Prolia | Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set | 15900 percentage change (%)*day | Geometric Coefficient of Variation 14 |
95% CI: [0.98, 1.01]ANCOVA
90% CI: [0.98, 1.01]ANCOVA
Primary
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.
Time frame: Baseline (pre-dose Day 1), up to Week 26
Population: Participants in the Pharmacokinetic Analysis Set (PKS) who had valid assessments of AUCinf. The PKS is defined as participants who were randomized into TP1 and met the following criteria: at least one PK primary endpoint (Cmax or AUCinf) is evaluable, they received treatment according to protocol on Day 1 and they did not experience relevant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose | 370000 day*ng/mL | Geometric Coefficient of Variation 47.8 |
| EU-Prolia | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose | 365000 day*ng/mL | Geometric Coefficient of Variation 43.3 |
90% CI: [0.93, 1.05]ANCOVA
Primary
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.
Time frame: Baseline (pre-dose Day 1), up to Week 26
Population: Participants in the Pharmacokinetic Analysis Set (PKS) who had valid assessments of Cmax. The PKS is defined as participants who were randomized into TP1 and met the following criteria: at least one PK primary endpoint (Cmax or AUCinf) is evaluable, they received treatment according to protocol on Day 1 and they did not experience relevant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose | 6970 ng/mL | Geometric Coefficient of Variation 45.8 |
| EU-Prolia | Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose | 7050 ng/mL | Geometric Coefficient of Variation 44.2 |
90% CI: [0.92, 1.03]ANCOVA
Primary
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.
Time frame: Baseline (screening), up to Week 52
Population: Per-Protocol Set (PPS) defined as participants who were randomized into TP1 and met the following criteria: the LS-BMD assessments at baseline and Week 52 are available, they received treatment according to protocol on Day 1 and Week 26 and they did not experience relevant protocol deviations which would affect LS-BMD up to Week 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set | 4.955 Percentage change (%) | Standard Error 0.2634 |
| EU-Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set | 5.099 Percentage change (%) | Standard Error 0.2618 |
95% CI: [-0.798, 0.509]Mixed-model repeated measures (MMRM)
Primary
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.
Time frame: Baseline (screening), up to Week 52
Population: TP1 Full Analysis Set (TP1 FAS) defined as participants who were randomized into TP1, who received at least one dose of study drug and for whom at least one post-baseline LS-BMD value (either at Week 26 or Week 52 or at both visits) is available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set | 4.963 Percentage change (%) | Standard Error 0.263 |
| EU-Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set | 5.140 Percentage change (%) | Standard Error 0.2627 |
95% CI: [-0.83, 0.475]Mixed-model repeated measures (MMRM)
Secondary
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.
Time frame: Week 56, Week 65 and Week 78
Population: The overall number of participants analyzed represents the TP2 Full Analysis Set (TP2 FAS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 0.0335 ng/mL | Standard Deviation 0.00714 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 0.0335 ng/mL | Standard Deviation 0.00685 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 0.125 ng/mL | Standard Deviation 0.19 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 0.0352 ng/mL | Standard Deviation 0.0159 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 0.0358 ng/mL | Standard Deviation 0.0259 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 0.144 ng/mL | Standard Deviation 0.155 |
| EU-Prolia/GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 0.0330 ng/mL | Standard Deviation 0 |
| EU-Prolia/GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 0.101 ng/mL | Standard Deviation 0.149 |
| EU-Prolia/GP2411 | CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 0.0359 ng/mL | Standard Deviation 0.0281 |
Secondary
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.
Time frame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
Population: The overall number of participants analyzed represents the Pharmacodynamic Analysis Set (PDS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Baseline | 0.437 ng/mL | Standard Deviation 0.249 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 0.0339 ng/mL | Standard Deviation 0.0134 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 2 | 0.0904 ng/mL | Standard Deviation 0.11 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 0.0383 ng/mL | Standard Deviation 0.0272 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 0.0355 ng/mL | Standard Deviation 0.0205 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 0.0428 ng/mL | Standard Deviation 0.0546 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 0.0661 ng/mL | Standard Deviation 0.0954 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 0.0342 ng/mL | Standard Deviation 0.0116 |
| GP2411 | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 0.0845 ng/mL | Standard Deviation 0.116 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 0.0345 ng/mL | Standard Deviation 0.011 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 0.0422 ng/mL | Standard Deviation 0.0406 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Baseline | 0.450 ng/mL | Standard Deviation 0.264 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 0.0407 ng/mL | Standard Deviation 0.0537 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 2 | 0.0859 ng/mL | Standard Deviation 0.0923 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 0.0651 ng/mL | Standard Deviation 0.0708 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 0.0332 ng/mL | Standard Deviation 0.00334 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 0.0807 ng/mL | Standard Deviation 0.0883 |
| EU-Prolia | CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 0.0362 ng/mL | Standard Deviation 0.0225 |
Secondary
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.
Time frame: Week 56, Week 65 and Week 78
Population: The overall number of participants analyzed represents the TP2 Full Analysis Set (TP2 FAS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 1540 ng/mL | Standard Deviation 880 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 6010 ng/mL | Standard Deviation 2200 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 122 ng/mL | Standard Deviation 406 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 1330 ng/mL | Standard Deviation 753 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 5550 ng/mL | Standard Deviation 1900 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 53.2 ng/mL | Standard Deviation 133 |
| EU-Prolia/GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 6220 ng/mL | Standard Deviation 2130 |
| EU-Prolia/GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 147 ng/mL | Standard Deviation 652 |
| EU-Prolia/GP2411 | Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 1640 ng/mL | Standard Deviation 962 |
Secondary
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.
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
Population: The overall number of participants analyzed represents the Pharmacokinetic Analysis Set (PKS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 208 ng/mL | Standard Deviation 277 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 1 | 6820 ng/mL | Standard Deviation 3220 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 1490 ng/mL | Standard Deviation 902 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 2 | 6940 ng/mL | Standard Deviation 3040 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 536 ng/mL | Standard Deviation 516 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 3160 ng/mL | Standard Deviation 1500 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 91.9 ng/mL | Standard Deviation 186 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 14 | 1130 ng/mL | Standard Deviation 740 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 4930 ng/mL | Standard Deviation 2530 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| GP2411 | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 95.9 ng/mL | Standard Deviation 415 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 1 | 0.928 ng/mL | Standard Deviation 14.9 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 495 ng/mL | Standard Deviation 487 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 198 ng/mL | Standard Deviation 392 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 47.9 ng/mL | Standard Deviation 114 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 1390 ng/mL | Standard Deviation 787 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 58.3 ng/mL | Standard Deviation 126 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 5250 ng/mL | Standard Deviation 2660 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 1 | 6890 ng/mL | Standard Deviation 3320 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 2 | 6760 ng/mL | Standard Deviation 2890 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 3070 ng/mL | Standard Deviation 1510 |
| EU-Prolia | Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 14 | 1090 ng/mL | Standard Deviation 797 |
Secondary
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.
Time frame: From Week 56 up to Week 78
Population: All participants in the TP2 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA titer positive | 0 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive | 42 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | NAb positive | 1 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Persistent | 3 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Transient | 39 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA titer positive | 1 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Persistent | 3 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive | 26 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | NAb positive | 0 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Transient | 23 Participants |
| EU-Prolia/GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | NAb positive | 1 Participants |
| EU-Prolia/GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Transient | 26 Participants |
| EU-Prolia/GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive | 26 Participants |
| EU-Prolia/GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA Positive, Persistent | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2 | ADA titer positive | 0 Participants |
Secondary
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.
Time frame: From Week 2 up to Week 52
Population: All participants in the TP1 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive | 93 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive, Persistent | 7 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive, Transient | 86 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA titer positive | 2 Participants |
| GP2411 | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | NAb positive | 3 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA titer positive | 2 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive, Transient | 104 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive | 108 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | NAb positive | 1 Participants |
| EU-Prolia | Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1 | ADA Positive, Persistent | 4 Participants |
Secondary
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.
Time frame: From dosing of study treatment at Week 52 up to Week 78
Population: All participants in the TP2 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 3 | 0 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 2 | 0 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 4 | 0 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 1 | 1 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 4 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 1 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 2 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 3 | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 1 | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 3 | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 4 | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2 | ISR Grade 2 | 0 Participants |
Secondary
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.
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Population: All participants in the TP1 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 1 | 6 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 3 | 0 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 2 | 1 Participants |
| GP2411 | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 4 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 4 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 2 | 1 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 3 | 0 Participants |
| EU-Prolia | Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1 | ISR Grade 1 | 9 Participants |
Secondary
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.
Time frame: From dosing of study treatment at Week 52 up to Week 78
Population: All participants in the TP2 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hand fracture | 0 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hip fracture | 1 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Fibula fracture | 1 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hand fracture | 0 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Fibula fracture | 0 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hip fracture | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Fibula fracture | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hand fracture | 1 Participants |
| EU-Prolia/GP2411 | Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Hip fracture | 0 Participants |
Secondary
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.
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Population: All participants in the TP1 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Wrist fracture | 1 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Femoral neck fracture | 1 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Femur fracture | 0 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Radius fracture | 0 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Ankle fracture | 1 Participants |
| GP2411 | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Hip fracture | 2 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Ankle fracture | 1 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Hip fracture | 0 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Wrist fracture | 0 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Radius fracture | 1 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Femoral neck fracture | 0 Participants |
| EU-Prolia | Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1 | Femur fracture | 1 Participants |
Secondary
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.
Time frame: From dosing of study treatment at Week 52 up to Week 78
Population: TP2 Safety Analysis Set defined as participants who received at least one dose of study drug in Treatment Period 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | TEAE | 68 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related TEAE | 7 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Serious TEAE | 4 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related serious TEAE | 0 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related serious TEAE | 0 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | TEAE | 47 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Serious TEAE | 2 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related TEAE | 7 Participants |
| EU-Prolia/GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related serious TEAE | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Treatment-related TEAE | 5 Participants |
| EU-Prolia/GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | Serious TEAE | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2 | TEAE | 48 Participants |
Secondary
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.
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Population: TP1 Safety Analysis Set defined as participants who received at least one dose of study drug in Treatment Period 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Serious TEAE | 12 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Treatment-related TEAE | 36 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Treatment-related serious TEAE | 0 Participants |
| GP2411 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | TEAE | 157 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Treatment-related serious TEAE | 0 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Treatment-related TEAE | 49 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | Serious TEAE | 8 Participants |
| EU-Prolia | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1 | TEAE | 181 Participants |
Secondary
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.
Time frame: Week 52 and Week 78
Population: All participants in the TP2 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Worsening vertebral fractures at Week 78 | 1 Participants |
| GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | New vertebral fractures at Week 78 | 12 Participants |
| GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | At least one vertebral fracture at Week 52 | 126 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Worsening vertebral fractures at Week 78 | 0 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | At least one vertebral fracture at Week 52 | 57 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | New vertebral fractures at Week 78 | 3 Participants |
| EU-Prolia/GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | Worsening vertebral fractures at Week 78 | 0 Participants |
| EU-Prolia/GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | New vertebral fractures at Week 78 | 8 Participants |
| EU-Prolia/GP2411 | Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2 | At least one vertebral fracture at Week 52 | 65 Participants |
Secondary
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.
Time frame: Baseline (screening) and Week 52
Population: All participants in the TP1 Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2411 | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | New vertebral fractures at Week 52 | 15 Participants |
| GP2411 | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | At least one vertebral fracture at baseline | 123 Participants |
| GP2411 | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | Worsening vertebral fractures at Week 52 | 3 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | New vertebral fractures at Week 52 | 24 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | At least one vertebral fracture at baseline | 116 Participants |
| EU-Prolia | Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1 | Worsening vertebral fractures at Week 52 | 3 Participants |
Secondary
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.
Time frame: Baseline (screening), Week 26 and Week 52
Population: The overall number of participants analyzed represents the Per-Protocol Set (PPS). The number analyzed per row represents participants with data at baseline and at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 26 | 2.0818 percentage change (%) | Standard Deviation 3.38039 |
| GP2411 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 52 | 2.4200 percentage change (%) | Standard Deviation 3.70552 |
| EU-Prolia | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 26 | 1.8087 percentage change (%) | Standard Deviation 3.18505 |
| EU-Prolia | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 52 | 2.6157 percentage change (%) | Standard Deviation 3.26119 |
Secondary
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.
Time frame: Baseline (screening), Week 26 and Week 52
Population: The overall number of participants analyzed represents the TP1 Full Analysis Set (TP1 FAS). The number analyzed per row represents participants with data at baseline and at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | 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) | Week 26 | 2.0343 percentage change (%) | Standard Deviation 3.43682 |
| GP2411 | 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) | Week 52 | 2.3686 percentage change (%) | Standard Deviation 3.69145 |
| EU-Prolia | 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) | Week 26 | 1.8210 percentage change (%) | Standard Deviation 3.11073 |
| EU-Prolia | 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) | Week 52 | 2.5717 percentage change (%) | Standard Deviation 3.29726 |
Secondary
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.
Time frame: Baseline (screening), Week 78
Population: Participants in the TP2 Full Analysis Set (TP2 FAS) who had valid assessments of the outcome measure at both baseline and Week 78.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 3.2220 Percentage change (%) | Standard Deviation 4.03733 |
| EU-Prolia | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 2.9406 Percentage change (%) | Standard Deviation 3.92115 |
| EU-Prolia/GP2411 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 2.6857 Percentage change (%) | Standard Deviation 3.64193 |
Secondary
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.
Time frame: Baseline (screening), Week 26
Population: Participants in the Per-Protocol Set (PPS) who had valid assessments of the outcome measure at both baseline and Week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set) | 3.6501 percentage change (%) | Standard Deviation 3.76952 |
| EU-Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set) | 3.6700 percentage change (%) | Standard Deviation 3.68816 |
Secondary
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.
Time frame: Baseline (screening), Week 26
Population: Participants in the TP1 Full Analysis Set (TP1 FAS) who had valid assessments of the outcome measure at both baseline and Week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set) | 3.5877 percentage change (%) | Standard Deviation 3.73579 |
| EU-Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set) | 3.7144 percentage change (%) | Standard Deviation 3.8973 |
Secondary
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.
Time frame: Baseline (screening), Week 78
Population: Participants in the TP2 Full Analysis Set (TP2 FAS) who had valid assessments of the outcome measure at both baseline and Week 78. TP2 FAS is defined as participants who were re-randomized into TP2 and for whom at least one TP2 efficacy, pharmacokinetics or pharmacodynamics value is available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 6.8222 Percentage change (%) | Standard Deviation 3.95225 |
| EU-Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 7.0694 Percentage change (%) | Standard Deviation 4.72955 |
| EU-Prolia/GP2411 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 6.4212 Percentage change (%) | Standard Deviation 4.47102 |
Secondary
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.
Time frame: Baseline (screening), Week 26 and Week 52
Population: The overall number of participants analyzed represents the Per-Protocol Set (PPS). The number analyzed per row represents participants with data at baseline and at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 26 | 2.6475 percentage change (%) | Standard Deviation 2.43928 |
| GP2411 | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 52 | 3.4289 percentage change (%) | Standard Deviation 2.71152 |
| EU-Prolia | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 26 | 2.1178 percentage change (%) | Standard Deviation 2.44627 |
| EU-Prolia | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set) | Week 52 | 3.3211 percentage change (%) | Standard Deviation 2.59266 |
Secondary
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.
Time frame: Baseline (screening), Week 26 and Week 52
Population: The overall number of participants analyzed represents the TP1 Full Analysis Set (TP1 FAS). The number analyzed per row represents participants with data at baseline and at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | 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) | Week 26 | 2.5280 percentage change (%) | Standard Deviation 2.46669 |
| GP2411 | 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) | Week 52 | 3.2882 percentage change (%) | Standard Deviation 2.7026 |
| EU-Prolia | 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) | Week 26 | 2.0595 percentage change (%) | Standard Deviation 2.51811 |
| EU-Prolia | 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) | Week 52 | 3.2234 percentage change (%) | Standard Deviation 2.64633 |
Secondary
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.
Time frame: Baseline (screening), Week 78
Population: Participants in the TP2 Full Analysis Set (TP2 FAS) who had valid assessments of the outcome measure at both baseline and Week 78.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2411 | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 3.8270 Percentage change (%) | Standard Deviation 3.28071 |
| EU-Prolia | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 4.0898 Percentage change (%) | Standard Deviation 2.9653 |
| EU-Prolia/GP2411 | Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set) | 3.9987 Percentage change (%) | Standard Deviation 3.33311 |
Secondary
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.
Time frame: Week 56, Week 65 and Week 78
Population: The overall number of participants analyzed represents the TP2 Full Analysis Set (TP2 FAS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 10.5 ng/mL | Standard Deviation 3.4 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 13.7 ng/mL | Standard Deviation 8.06 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 17.5 ng/mL | Standard Deviation 14.1 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 10.9 ng/mL | Standard Deviation 3.43 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 13.9 ng/mL | Standard Deviation 5.39 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 20.3 ng/mL | Standard Deviation 20.4 |
| EU-Prolia/GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 56 | 14.4 ng/mL | Standard Deviation 11 |
| EU-Prolia/GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 78 | 17.1 ng/mL | Standard Deviation 8.37 |
| EU-Prolia/GP2411 | PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2 | Week 65 | 11.1 ng/mL | Standard Deviation 3.85 |
Secondary
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.
Time frame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
Population: The overall number of participants analyzed represents the Pharmacodynamic Analysis Set (PDS). The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 56.8 ng/mL | Standard Deviation 23.2 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 13.5 ng/mL | Standard Deviation 5.92 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Baseline | 60.3 ng/mL | Standard Deviation 27.1 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 15.4 ng/mL | Standard Deviation 7.44 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 21.2 ng/mL | Standard Deviation 9.53 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 10.5 ng/mL | Standard Deviation 3.14 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 2 | 58.5 ng/mL | Standard Deviation 25.9 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 15.0 ng/mL | Standard Deviation 5.95 |
| GP2411 | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 12.1 ng/mL | Standard Deviation 4.52 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 52 | 15.7 ng/mL | Standard Deviation 7.11 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 2 | 60.2 ng/mL | Standard Deviation 29.3 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Day 4 | 58.8 ng/mL | Standard Deviation 26.8 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 8 | 21.0 ng/mL | Standard Deviation 7.58 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 18 | 12.6 ng/mL | Standard Deviation 5.1 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 22 | 13.3 ng/mL | Standard Deviation 4.59 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 26 | 15.9 ng/mL | Standard Deviation 6.71 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Week 39 | 10.7 ng/mL | Standard Deviation 3.43 |
| EU-Prolia | PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1 | Baseline | 62.2 ng/mL | Standard Deviation 30 |