Postmenopausal Women With Osteoporosis
Conditions
Brief summary
This study is a Double-blind, Randomized, Active-controlled, Phase 3 Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety of CT-P41 and US-licensed Prolia in Postmenopausal Women with Osteoporosis
Detailed description
This is a double-blind, randomized, active-controlled, Phase 3 study to evaluate the efficacy, PK, PD, and safety including immunogenicity of CT-P41 compared with US-licensed Prolia in postmenopausal women with osteoporosis. All patients will also receive daily supplementation containing at least 1,000 mg of elemental calcium and at least 400 IU vitamin D from randomization to EOS visit and the data will be collected via patient's diary.
Interventions
BIOLOGICALCT-P41
60 mg/mL single dose, Solution for injection in PFS
BIOLOGICALUS-licensed Prolia
60 mg/mL single dose, Solution for injection in PFS
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Women, 50 to 80 years of age, both inclusive. 2. Body weight between 40.0 and 99.9 kg, both inclusive, when rounded to the nearest tenth. 3. Postmenopausal 4. Bone mineral density T-score ≤ - 2.5 and ≥ - 4.0 at the lumbar spine (L1 to L4) as assessed by the central imaging vendor based on dual-energy X-ray absorptiometry(DXA) scan. 5. Patients must have at least 3 vertebrae considered evaluable at the lumbar spine (L1 to L4) and at least 1 hip considered evaluable by DXA scan assessed by the central imaging vendor. Patients with unilateral metal in hips that would be allowed for the other side of 1 evaluable hip are included. 6. Patient with albumin-adjusted total serum calcium ≥ 8.5 mg/dL (≥ 2.125 mmol/L) at Screening.
Exclusion criteria
1. Patient previously received denosumab, any other monoclonal antibodies, or biologic agents for osteoporosis 2. Patient confirmed or suspected with infection of COVID-19 at Screening, or has contact with COVID-19 patient within 14 days from Screening 3. Patient with history and/or presence of one severe or \> 2 moderate vertebral fractures as determined by central reading of lateral spine X-ray 4. Patient with history and/or presence of hip fracture 5. Patient with history and/or presence of hyperparathyroidism or hypoparathyroidism, irrespective of current controlled or uncontrolled status 6. Patient with current hyperthyroidism (unless well controlled on stable antithyroid therapy) 7. Patient with current hypothyroidism (unless well controlled on stable thyroid replacement therapy) 8. Patient with history and/or presence of bone disease and metabolic disease (except for osteoporosis) that may interfere with the interpretation of the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 - Full Analysis Set (FAS) | baseline (screening), Week 52 predose | Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA) and assessments of the lumbar spine (L1 to L4) were performed at a central imaging vendor. To evaluate the difference between 2 groups in the primary efficacy endpoint, the percent change from baseline in BMD for lumbar spine (L1 to L4) by DXA at Week 52 was analyzed using an analysis of covariance (ANCOVA) model coupled with multiple imputation assuming the data to be missing at random (MAR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | baseline (screening), Week 52 predose | Bone mineral density was assessed by DXA and assessments of the lumbar spine (L1 to L4), total hip, and femoral neck were performed at a central imaging vendor. |
| Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | baseline (screening), Week 78 | Bone mineral density was assessed by DXA and assessments of the lumbar spine (L1 to L4), total hip, and femoral neck BMD were performed at a central imaging vendor. |
| Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | up to Week 52 predose | Efficacy analysis of new vertebral fractures included only vertebral fractures occurring from T4 to L4 and confirmed by the central imaging vendor. A new vertebral fracture was defined as an increase of ≥1 grade in any vertebra from T4 to L4 that was normal at screening. The nonvertebral fractures endpoint included fractures other than those of the vertebrae, excluding the skull, facial bones, mandible, metacarpals, and phalanges (fingers or toes) since they are not associated with decreased BMD, and excluded pathologic fractures and those associated with severe trauma acquired from a fall (from a height higher than a stool, chair, or first rung of a ladder) or otherwise. Only nonvertebral fractures confirmed by the central imaging vendor were included in the efficacy analysis. The fractures occurring at the site of femur neck, femur intertrochanter, or femur subtrochanter were considered as a hip fracture. |
| Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | from Week 52 to Week 78 | Efficacy analysis of new vertebral fractures included only vertebral fractures occurring from T4 to L4 and confirmed by the central imaging vendor. A new vertebral fracture was defined as an increase of ≥1 grade in any vertebra from T4 to L4 that was normal at screening. The nonvertebral fractures endpoint included fractures other than those of the vertebrae, excluding the skull, facial bones, mandible, metacarpals, and phalanges (fingers or toes) since they are not associated with decreased BMD, and excluded pathologic fractures and those associated with severe trauma acquired from a fall (from a height higher than a stool, chair, or first rung of a ladder) or otherwise. Only nonvertebral fractures confirmed by the central imaging vendor were included in the efficacy analysis. The fractures occurring at the site of femur neck, femur intertrochanter, or femur subtrochanter were considered as a hip fracture. |
| Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set | Week 0 Day 1 predose, Week 26 predose | The Ctrough, a concentration before the next study drug administration, was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the lower limit of quantification (LLoQ) was set to 0 in the descriptive summaries of PK parameter estimation. In TP I, the Ctrough of denosumab at Weeks 0 and 26 was assessed as the serum concentration at Weeks 26 and 52 before the study drug administration, respectively. |
| Ctrough of Denosumab at Week 52 - PK-TP II Subset | Week 52 | The Ctrough, a concentration before the next study drug administration, was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the LLoQ was set to 0 in the descriptive summaries of PK parameter estimation. In TP II, the Ctrough of denosumab at Week 52 was assessed as the serum concentration at Week 78. |
| Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set | up to Week 52 predose | Samples that were positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment. The test outcomes for the screening assay were 'Positive' or 'Negative'. The number of patients with at least one ADA/NAb positive result after the first study drug administration of each treatment period including scheduled and unscheduled visits (Treatment Period I: Week 0 / Treatment Period II: Week 52) regardless of their ADA status at baseline were presented. |
| Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set | Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose) | Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100. |
| Percent Change From Baseline for Serum Concentration of s-CTX at Week 78 - PD-TP II Subset | Baseline (Week 0 Day 1 predose), Week 78 | Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100. |
| Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set | Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose) | Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100. |
| Percent Change From Baseline for Serum Concentration of P1NP at Week 78 - PD-TP II Subset | Baseline (Week 0 Day 1 predose), Week 78 | Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100. |
| Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | from Week 52 to Week 78 | Samples that were positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment. The test outcomes for the screening assay were 'Positive' or 'Negative'. The number of patients with at least one ADA/NAb positive result after the first study drug administration of each treatment period including scheduled and unscheduled visits (Treatment Period I: Week 0 / Treatment Period II: Week 52) regardless of their ADA status at baseline were presented. |
| Maximum Serum Concentration (Cmax) of Denosumab After First Dose - PK Set | from baseline (Week 0 Day 1 predose) to Week 26 predose | Cmax was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the LLoQ was set to 0 in the descriptive summaries of PK parameter estimation. |
Countries
Estonia, Latvia, Poland, Ukraine
Participant flow
Recruitment details
The recruitment was conducted in 20 study centers in 4 countries.
Pre-assignment details
The screening period began after the participants had signed the written informed consent form and completed it within 28 days before the 1st randomization (Week 0 Day 1). On Week 0 Day 1, participants were randomized in a 1:1 ratio to receive CT-P41 or US-Prolia during Treatment Period (TP) I. At Week 52 predose, participants in the US-Prolia group were re-randomized 1:1 to either continue US-Prolia or transition to CT-P41. The participants in the CT-P41 group continued with CT-P41 for TP II.
Participants by arm
| Arm | Count |
|---|---|
| CT-P41 A total of 2 subcutaneous administration of 60 mg CT-P41 (proposed denosumab biosimilar) at Week 0 and Week 26 (26-week intervals) in TP I
CT-P41: 60 mg/mL single dose, Solution for injection in PFS | 240 |
| US-licensed Prolia A total of 2 subcutaneous administration of 60 mg US-licensed Prolia (denosumab) at Week 0 and Week 26 (26-week intervals) in TP I
US-licensed Prolia: 60 mg/mL single dose, Solution for injection in PFS | 239 |
| Total | 479 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| TP II - Week 52 to Week 78 | Discontinued the study treatment before the study treatment initiation due to the adverse event | 0 | 0 | 1 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Adverse Event | 4 | 5 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Disease progression | 0 | 1 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Lost to Follow-up | 0 | 3 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Protocol Violation | 5 | 4 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Terminated the study before the initiation of the study treatment | 1 | 1 | 0 | 0 | 0 |
| TP I - Week 0, Day 1 to Week 52 Predose | Withdrawal by Subject | 8 | 24 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | CT-P41 | US-licensed Prolia | Total |
|---|---|---|---|
| Age, Continuous | 66.0 years | 66.0 years | 66.0 years |
| Body mass index | 24.92 kg/m2 STANDARD_DEVIATION 4.23 | 25.23 kg/m2 STANDARD_DEVIATION 4.328 | 25.08 kg/m2 STANDARD_DEVIATION 4.277 |
| Race/Ethnicity, Customized Ethnicity - Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity - Non-Hispanic or Non-Latino | 240 Participants | 236 Participants | 476 Participants |
| Race/Ethnicity, Customized Race - White | 240 Participants | 239 Participants | 479 Participants |
| Sex: Female, Male Female | 240 Participants | 239 Participants | 479 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 / 239 | 0 / 238 | 1 / 220 | 0 / 100 | 0 / 101 |
| other Total, other adverse events | 98 / 239 | 86 / 238 | 44 / 220 | 14 / 100 | 29 / 101 |
| serious Total, serious adverse events | 7 / 239 | 10 / 238 | 8 / 220 | 3 / 100 | 0 / 101 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 - Full Analysis Set (FAS)
Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA) and assessments of the lumbar spine (L1 to L4) were performed at a central imaging vendor. To evaluate the difference between 2 groups in the primary efficacy endpoint, the percent change from baseline in BMD for lumbar spine (L1 to L4) by DXA at Week 52 was analyzed using an analysis of covariance (ANCOVA) model coupled with multiple imputation assuming the data to be missing at random (MAR).
Time frame: baseline (screening), Week 52 predose
Population: The FAS was defined as all participants who received at least 1 full dose of the study drug (CT-P41 or US-licensed Prolia). The total number of participants in FAS was 239 and 238 in the CT-P41 and US-licensed Prolia groups, respectively. The overall number of participants analyzed represents the number of participants in FAS who had a BMD assessment result for the lumbar spine by DXA at Week 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CT-P41 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 - Full Analysis Set (FAS) | 4.9597 percentage change (%) | Standard Error 0.29977 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 - Full Analysis Set (FAS) | 5.1528 percentage change (%) | Standard Error 0.32133 |
90% CI: [-0.76, 0.38]ANCOVA
Secondary
Ctrough of Denosumab at Week 52 - PK-TP II Subset
The Ctrough, a concentration before the next study drug administration, was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the LLoQ was set to 0 in the descriptive summaries of PK parameter estimation. In TP II, the Ctrough of denosumab at Week 52 was assessed as the serum concentration at Week 78.
Time frame: Week 52
Population: The PK-TP II subset was defined as all participants in the PK set who received 1 full dose of the study drug (CT-P41 or US-licensed Prolia) at Week 52 and had at least 1 post-treatment PK concentration data with a concentration above the LLoQ after Week 52. The overall number of participants analyzed row represents the number of participants in the PK-TP II subset who had the Ctrough data at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P41 | Ctrough of Denosumab at Week 52 - PK-TP II Subset | 70.24 ng/mL | Standard Deviation 126.852 |
| US-licensed Prolia | Ctrough of Denosumab at Week 52 - PK-TP II Subset | 66.60 ng/mL | Standard Deviation 129.573 |
| Switched to CT-P41 | Ctrough of Denosumab at Week 52 - PK-TP II Subset | 126.15 ng/mL | Standard Deviation 508.689 |
Secondary
Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS
Efficacy analysis of new vertebral fractures included only vertebral fractures occurring from T4 to L4 and confirmed by the central imaging vendor. A new vertebral fracture was defined as an increase of ≥1 grade in any vertebra from T4 to L4 that was normal at screening. The nonvertebral fractures endpoint included fractures other than those of the vertebrae, excluding the skull, facial bones, mandible, metacarpals, and phalanges (fingers or toes) since they are not associated with decreased BMD, and excluded pathologic fractures and those associated with severe trauma acquired from a fall (from a height higher than a stool, chair, or first rung of a ladder) or otherwise. Only nonvertebral fractures confirmed by the central imaging vendor were included in the efficacy analysis. The fractures occurring at the site of femur neck, femur intertrochanter, or femur subtrochanter were considered as a hip fracture.
Time frame: up to Week 52 predose
Population: The overall number of participants analyzed and the number analyzed represents the total number of participants in FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | New vertebral fracture | 1 Participants |
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | Nonvertebral fracture | 2 Participants |
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | Hip fracture | 0 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | New vertebral fracture | 1 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | Nonvertebral fracture | 4 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP I - FAS | Hip fracture | 0 Participants |
Secondary
Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset
Efficacy analysis of new vertebral fractures included only vertebral fractures occurring from T4 to L4 and confirmed by the central imaging vendor. A new vertebral fracture was defined as an increase of ≥1 grade in any vertebra from T4 to L4 that was normal at screening. The nonvertebral fractures endpoint included fractures other than those of the vertebrae, excluding the skull, facial bones, mandible, metacarpals, and phalanges (fingers or toes) since they are not associated with decreased BMD, and excluded pathologic fractures and those associated with severe trauma acquired from a fall (from a height higher than a stool, chair, or first rung of a ladder) or otherwise. Only nonvertebral fractures confirmed by the central imaging vendor were included in the efficacy analysis. The fractures occurring at the site of femur neck, femur intertrochanter, or femur subtrochanter were considered as a hip fracture.
Time frame: from Week 52 to Week 78
Population: The overall number of participants analyzed and the number analyzed represents the total number of participants in FAS-TP II subset.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Nonvertebral fracture | 2 Participants |
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | New vertebral fracture | 1 Participants |
| CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Hip fracture | 0 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Nonvertebral fracture | 0 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | New vertebral fracture | 0 Participants |
| US-licensed Prolia | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Hip fracture | 0 Participants |
| Switched to CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | New vertebral fracture | 0 Participants |
| Switched to CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Hip fracture | 0 Participants |
| Switched to CT-P41 | Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset | Nonvertebral fracture | 1 Participants |
Secondary
Maximum Serum Concentration (Cmax) of Denosumab After First Dose - PK Set
Cmax was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the LLoQ was set to 0 in the descriptive summaries of PK parameter estimation.
Time frame: from baseline (Week 0 Day 1 predose) to Week 26 predose
Population: Participants in the PK Set who had assessments of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CT-P41 | Maximum Serum Concentration (Cmax) of Denosumab After First Dose - PK Set | 5851.2 ng/mL | Geometric Coefficient of Variation 32.2 |
| US-licensed Prolia | Maximum Serum Concentration (Cmax) of Denosumab After First Dose - PK Set | 5492.7 ng/mL | Geometric Coefficient of Variation 29.8 |
Secondary
Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset
Samples that were positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment. The test outcomes for the screening assay were 'Positive' or 'Negative'. The number of patients with at least one ADA/NAb positive result after the first study drug administration of each treatment period including scheduled and unscheduled visits (Treatment Period I: Week 0 / Treatment Period II: Week 52) regardless of their ADA status at baseline were presented.
Time frame: from Week 52 to Week 78
Population: The Safety-TP II subset was defined as all participants in the Safety set who received 1 dose (full or partial) of study drug (CT-P41 or US-licensed Prolia) at Week 52. The overall number of participants analyzed and the number analyzed represents the number of participants in the Safety-TP II subset.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P41 | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | ADA positive | 208 Participants |
| CT-P41 | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | NAb positive | 0 Participants |
| US-licensed Prolia | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | ADA positive | 92 Participants |
| US-licensed Prolia | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | NAb positive | 0 Participants |
| Switched to CT-P41 | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | ADA positive | 93 Participants |
| Switched to CT-P41 | Number of Participants With at Least 1 ADA/NAb Result After the First Study Drug Administration of TP II - Safety-TP II Subset | NAb positive | 0 Participants |
Secondary
Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set
Samples that were positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment. The test outcomes for the screening assay were 'Positive' or 'Negative'. The number of patients with at least one ADA/NAb positive result after the first study drug administration of each treatment period including scheduled and unscheduled visits (Treatment Period I: Week 0 / Treatment Period II: Week 52) regardless of their ADA status at baseline were presented.
Time frame: up to Week 52 predose
Population: The Safety set was defined as all participants who received at least 1 dose (full or partial) of the study drug (CT-P41 or US-licensed Prolia). The overall number of participants analyzed and the number analyzed represents the total number of participants in the Safety Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P41 | Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set | NAb positive | 0 Participants |
| CT-P41 | Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set | ADA positive | 233 Participants |
| US-licensed Prolia | Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set | ADA positive | 234 Participants |
| US-licensed Prolia | Number of Participants With at Least 1 Anti-drug Antibodies (ADA)/Neutralizing Antibodies (NAb) Result After the First Study Drug Administration of TP I - Safety Set | NAb positive | 0 Participants |
Secondary
Percent Change From Baseline for Serum Concentration of P1NP at Week 78 - PD-TP II Subset
Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100.
Time frame: Baseline (Week 0 Day 1 predose), Week 78
Population: The overall number of participants analyzed represents the number of participants in the PD-TP II subset who had the P1NP value at baseline and Week 78.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P41 | Percent Change From Baseline for Serum Concentration of P1NP at Week 78 - PD-TP II Subset | -67.05 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of P1NP at Week 78 - PD-TP II Subset | -68.60 percentage change (%) |
| Switched to CT-P41 | Percent Change From Baseline for Serum Concentration of P1NP at Week 78 - PD-TP II Subset | -64.54 percentage change (%) |
Secondary
Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set
Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100.
Time frame: Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
Population: The overall number of participants analyzed represents the total number of participants in PD Set. The number analyzed per row represents the number of participants in PD set who had P1NP value at the corresponding time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CT-P41 | Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set | Week 26 | -69.31 percentage change (%) |
| CT-P41 | Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set | Week 52 | -69.99 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set | Week 26 | -68.22 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 26 and 52 - PD Set | Week 52 | -66.61 percentage change (%) |
Secondary
Percent Change From Baseline for Serum Concentration of s-CTX at Week 78 - PD-TP II Subset
Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100.
Time frame: Baseline (Week 0 Day 1 predose), Week 78
Population: The PD-TP II subset was defined as all participants in the PD set who received 1 full dose of the study drug (CT-P41 or US-licensed Prolia) at Week 52 and had at least 1 post-treatment PD concentration data with a concentration above the LLoQ after Week 52. The overall number of participants analyzed represents the number of participants in the PD-TP II subset who had s-CTX value at baseline and Week 78.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P41 | Percent Change From Baseline for Serum Concentration of s-CTX at Week 78 - PD-TP II Subset | -70.4609 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of s-CTX at Week 78 - PD-TP II Subset | -64.9063 percentage change (%) |
| Switched to CT-P41 | Percent Change From Baseline for Serum Concentration of s-CTX at Week 78 - PD-TP II Subset | -70.1268 percentage change (%) |
Secondary
Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set
Serum concentration below the LLoQ was set to the LLoQ. The percent change from baseline for serum concentration at each visit was calculated as (\[Result at each visit - Result at Baseline\] / Result at Baseline) × 100.
Time frame: Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
Population: The PD set was defined as all participants who received a full dose of the study drug (CT-P41 or US-licensed Prolia) at Day 1 (Week 0) and had at least 1 post-treatment PD concentration data with a concentration above the LLoQ before dosing at Week 52. The overall number of participants analyzed represents the total number of participants in PD set. The number analyzed per row represents the number of participants in the PD set who had the data at the corresponding time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CT-P41 | Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set | Week 26 | -75.6972 percentage change (%) |
| CT-P41 | Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set | Week 52 | -72.7506 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set | Week 26 | -74.3547 percentage change (%) |
| US-licensed Prolia | Percent Change From Baseline for Serum Concentration of Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Weeks 26 and 52 - Pharmacodynamic (PD) Set | Week 52 | -72.5275 percentage change (%) |
Secondary
Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS
Bone mineral density was assessed by DXA and assessments of the lumbar spine (L1 to L4), total hip, and femoral neck were performed at a central imaging vendor.
Time frame: baseline (screening), Week 52 predose
Population: The overall number of participants analyzed row represents the total number of participants in the FAS. The number analyzed per row represents the number of participants in FAS with lumbar spine, total hip, or femoral neck BMD value at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Femoral neck | 2.2295 percentage change (%) | Standard Deviation 4.02031 |
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Lumbar spine | 5.4913 percentage change (%) | Standard Deviation 3.79907 |
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Total hip | 2.7914 percentage change (%) | Standard Deviation 2.87044 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Lumbar spine | 5.6621 percentage change (%) | Standard Deviation 3.75768 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Total hip | 2.4253 percentage change (%) | Standard Deviation 2.84061 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 52 - FAS | Femoral neck | 1.9476 percentage change (%) | Standard Deviation 3.86739 |
Secondary
Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset
Bone mineral density was assessed by DXA and assessments of the lumbar spine (L1 to L4), total hip, and femoral neck BMD were performed at a central imaging vendor.
Time frame: baseline (screening), Week 78
Population: The FAS-TP II subset was defined as all participants in FAS who received 1 full dose of the study drug (CT-P41 or US-licensed Prolia) at Week 52. The overall number of participants analyzed row represents the total number of participants in the FAS-TP II subset. The number analyzed per row represents the number of participants in FAS-TP II subset with lumbar spine, total hip, or femoral neck BMD value at baseline and Week 78.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Total hip | 3.4706 percentage change (%) | Standard Deviation 2.81017 |
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Lumbar spine | 6.8588 percentage change (%) | Standard Deviation 4.12795 |
| CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Femoral neck | 2.9995 percentage change (%) | Standard Deviation 3.73072 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Total hip | 2.7947 percentage change (%) | Standard Deviation 2.79862 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Lumbar spine | 6.5745 percentage change (%) | Standard Deviation 3.40437 |
| US-licensed Prolia | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Femoral neck | 2.4429 percentage change (%) | Standard Deviation 3.61786 |
| Switched to CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Lumbar spine | 7.0532 percentage change (%) | Standard Deviation 3.55985 |
| Switched to CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Femoral neck | 2.8226 percentage change (%) | Standard Deviation 4.02021 |
| Switched to CT-P41 | Percent Change From Baseline in Lumbar Spine, Total Hip, and Femoral Neck BMD at Week 78 - FAS-TP II Subset | Total hip | 3.3837 percentage change (%) | Standard Deviation 2.92786 |
Secondary
Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set
The Ctrough, a concentration before the next study drug administration, was calculated by non-compartmental analysis method from the concentration-time data. All serum concentrations below the lower limit of quantification (LLoQ) was set to 0 in the descriptive summaries of PK parameter estimation. In TP I, the Ctrough of denosumab at Weeks 0 and 26 was assessed as the serum concentration at Weeks 26 and 52 before the study drug administration, respectively.
Time frame: Week 0 Day 1 predose, Week 26 predose
Population: The PK Set was defined as all participants who received at least 1 full dose of the study drug (CT-P41 or US-licensed Prolia) and had at least 1 post-treatment PK concentration data with a concentration above the LLoQ prior to dosing at Week 52. The overall number of participants analyzed row represents the total number of participants in PK Set. The number analyzed per row represents the number of participants in PK set with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P41 | Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set | Week 26 | 75.64 ng/mL | Standard Deviation 154.63 |
| CT-P41 | Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set | Week 0 Day 1 | 46.79 ng/mL | Standard Deviation 105.102 |
| US-licensed Prolia | Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set | Week 0 Day 1 | 31.69 ng/mL | Standard Deviation 73.253 |
| US-licensed Prolia | Trough Serum Concentration (Ctrough) of Denosumab at Weeks 0 and 26 - Pharmacokinetic (PK) Set | Week 26 | 63.99 ng/mL | Standard Deviation 140.912 |