Postmenopausal Women With OsteoporosisPhase 3NCT03974100
Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis
A Phase 3 study testing GP2411 and EU-Prolia (EU-authorized Prolia®) in people with Postmenopausal Women With Osteoporosis, run by Sandoz at 42 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 80 years, women only
- Conditions the study is for
- Postmenopausal Women With Osteoporosis
- What is being tested?
- GP2411 and EU-Prolia (EU-authorized Prolia®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 527 participants
- Where
- 42 sitesin 6 countries
- Study dates
- 2 Jul 2019to 22 Apr 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
42 sites in 6 countries.
42 sites in 6 countries
Poland10 sites
Sandoz Investigational Site
Bialystok, 15-351
Sandoz Investigational Site
Bialystok, 15-461
Sandoz Investigational Site
Bydgoszcz, 85 168
Sandoz Investigational Site
Krakow, Lesser Poland Voivodeship, 30-510
Sandoz Investigational Site
Lodz, 90 242
Sandoz Investigational Site
Nadarzyn, 05-830
Sandoz Investigational Site
Torun, 87-100
Sandoz Investigational Site
Warsaw, 00-874
Sandoz Investigational Site
Warsaw, 02 118
Sandoz Investigational Site
Warsaw, 02 691
Czechia9 sites
Sandoz Investigational Site
Brno, 602 00
Sandoz Investigational Site
Hradec Králové, CZE, 500 05
Sandoz Investigational Site
Ostrava, Czech Republic, 772 00
Sandoz Investigational Site
Ostrava, 702 00
Sandoz Investigational Site
Pardubice, 530 02
Sandoz Investigational Site
Pilsen, 30460
Sandoz Investigational Site
Prague, 128 50
Sandoz Investigational Site
Prague, 14900
Sandoz Investigational Site
Uherské Hradiště, 686 01
United States6 sites
Sandoz Investigational Site
Carrollton, Texas, 75010
Sandoz Investigational Site
Duncansville, Pennsylvania, 16635
Sandoz Investigational Site
Miami, Florida, 33135
Sandoz Investigational Site
Peoria, Arizona, 85381
Sandoz Investigational Site
Wichita, Kansas, 67207
Sandoz Investigational Site
Wyomissing, Pennsylvania, 19610
Bulgaria6 sites
Sandoz Investigational Site
Plovdiv, 4001
Sandoz Investigational Site
Plovdiv, 4002
Sandoz Investigational Site
Sofia, 1431
Sandoz Investigational Site
Sofia, 1505
Sandoz Investigational Site
Sofia, 1680
Sandoz Investigational Site
Sofia, 1784
Spain6 sites
Sandoz Investigational Site
Barcelona, 08041
Sandoz Investigational Site
Madrid, 28009
Sandoz Investigational Site
Sabadell, Barcelona, 08208
Sandoz Investigational Site
Santiago de Compostela, A Coruna, 15705
Sandoz Investigational Site
Santiago de Compostela, Galicia, 15706
Sandoz Investigational Site
Seville, 41010
Japan5 sites
Sandoz Investigational Site
Chuoh-ku, Tokyo, 104-0031
Sandoz Investigational Site
Fujimi, Saitama, 354-0021
Sandoz Investigational Site
Hachiōji, Tokyo, 192-0046
Sandoz Investigational Site
Kiyose, Tokyo, 204-0021
Sandoz Investigational Site
Shinagawa, Tokyo, 140-0014
About this study
Official title: A Randomized, Double-blind, Multicenter Integrated Phase I/III Study in Postmenopausal Women With Osteoporosis to Compare the Pharmacokinetics, Pharmacodynamics, Efficacy, Safety and Immunogenicity of GP2411 (Proposed Biosimilar Denosumab) and Prolia® (EU-authorized)
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).
Read the 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.
- Conditions
- Postmenopausal Women With Osteoporosis
- Being tested
- GP2411, EU-Prolia (EU-authorized Prolia®)
- Keywords
- Prolia, GP2411, denosumab, postmenopausal osteoporosis
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GP2411Biological
60 mg /mL subcutaneous injection every 6 months
EU-Prolia (EU-authorized Prolia®)Biological
60 mg /mL subcutaneous injection every 6 months
| Study group | Role | What they receive |
|---|---|---|
| GP2411 | Experimental | 60 mg /mL subcutaneous injection every 6 months Receives: Biological: GP2411 |
| EU authorized Prolia | Active comparator | 60 mg /mL subcutaneous injection every 6 months Receives: Biological: EU-Prolia (EU-authorized Prolia®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (screening), up to Week 52
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.
Measured: Baseline (screening), up to Week 52
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.
Measured: Baseline (pre-dose Day 1), up to Week 26
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.
Measured: Baseline (pre-dose Day 1), up to Week 26
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.
Measured: Baseline (pre-dose Day 1), up to Week 26
Secondary outcomes (25)
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.
Measured: Baseline (screening), Week 26
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.
Measured: Baseline (screening), Week 26
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.
Measured: Baseline (screening), Week 78
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.
Measured: Baseline (screening), Week 26 and Week 52
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.
Measured: Baseline (screening), Week 26 and Week 52
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.
Measured: Baseline (screening), Week 78
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.
Measured: Baseline (screening), Week 26 and Week 52
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.
Measured: Baseline (screening), Week 26 and Week 52
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.
Measured: Baseline (screening), Week 78
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.
Measured: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
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.
Measured: Week 56, Week 65 and Week 78
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.
Measured: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
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.
Measured: Week 56, Week 65 and Week 78
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.
Measured: From first dose of study treatment on Day 1 up to pre-dose at Week 52
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.
Measured: From dosing of study treatment at Week 52 up to Week 78
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.
Measured: Baseline (screening) and Week 52
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.
Measured: Week 52 and Week 78
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.
Measured: From first dose of study treatment on Day 1 up to pre-dose at Week 52
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.
Measured: From dosing of study treatment at Week 52 up to Week 78
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.
Measured: From first dose of study treatment on Day 1 up to pre-dose at Week 52
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.
Measured: From dosing of study treatment at Week 52 up to Week 78
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.
Measured: From Week 2 up to Week 52
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.
Measured: From Week 56 up to Week 78
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.
Measured: 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
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.
Measured: Week 56, Week 65 and Week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start2 Jul 2019
- Primary completion22 Apr 2022
- Study completion22 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postmenopausal Women With OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 527 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sandoz
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hexal AG
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03974100
- Sponsor's protocol ID
- CGP24112301
- Other IDs
- 2018-003523-11, 2018
- Status last verified
- Feb 2023
- First submitted
- 3 Jun 2019
- Last updated
- 8 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Multicenter Integrated Phase I/III Study in Postmenopausal Women With Osteoporosis to Compare the Pharmacokinetics, Pharmacodynamics, Efficacy, Safety and Immunogenicity of GP2411 (Proposed Biosimilar Denosumab) and Prolia® (EU-authorized)
- ClinicalTrials.gov ID
- NCT03974100
- Acronym / sponsor ID
- CGP24112301
- Conditions
- Postmenopausal Women With Osteoporosis
- Keywords
- Prolia, GP2411, denosumab, postmenopausal osteoporosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 527 participants (actual)
- Lead sponsor
- SandozIndustry (pharma, biotech, devices)
- Collaborators
- Hexal AG
- Study start
- 2 Jul 2019 (actual)
- Primary completion
- 22 Apr 2022 (actual)
- Study completion
- 22 Apr 2022 (actual)
- First posted
- 4 Jun 2019 (actual)
- Results
- Posted 8 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GP2411 | Experimental | Biological: GP241160 mg /mL subcutaneous injection every 6 months |
| EU authorized Prolia | Active comparator | Biological: EU-Prolia (EU-authorized Prolia®)60 mg /mL subcutaneous injection every 6 months |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GP241160 mg /mL subcutaneous injection every 6 months | Biological | GP2411 |
| EU-Prolia (EU-authorized Prolia®)60 mg /mL subcutaneous injection every 6 months | Biological | EU authorized Prolia |
Primary outcome
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
25 secondary outcomes
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set)
Time frame: Baseline (screening), Week 26
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set)
Time frame: Baseline (screening), Week 26
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Time frame: Baseline (screening), Week 78
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Time frame: Baseline (screening), Week 26 and Week 52
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)
Time frame: Baseline (screening), Week 26 and Week 52
Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Time frame: Baseline (screening), Week 78
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
Time frame: Baseline (screening), Week 26 and Week 52
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)
Time frame: Baseline (screening), Week 26 and Week 52
Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
Time frame: Baseline (screening), Week 78
CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Time frame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Time frame: Week 56, Week 65 and Week 78
PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
Time frame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Time frame: Week 56, Week 65 and Week 78
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2
Time frame: From dosing of study treatment at Week 52 up to Week 78
Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1
Time frame: Baseline (screening) and Week 52
Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Time frame: Week 52 and Week 78
Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
Time frame: From dosing of study treatment at Week 52 up to Week 78
Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1
Time frame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2
Time frame: From dosing of study treatment at Week 52 up to Week 78
Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1
Time frame: From Week 2 up to Week 52
Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2
Time frame: From Week 56 up to Week 78
Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
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
Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
Time frame: Week 56, Week 65 and Week 78
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
42 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GP2411 and EU-Prolia (EU-authorized Prolia®) in people with Postmenopausal Women With Osteoporosis, run by Sandoz at 42 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in Poland, Czechia, United States, Bulgaria, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set (time frame: Baseline (screening), up to Week 52). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2023.