A Phase 3 Study to Compare Between CT-P41 and US-licensed Prolia in Postmenopausal Women With Osteoporosis

Phase 3

Completed

• Conditions: Postmenopausal Women With Osteoporosis
• Interventions: Biological: CT-P41; Biological: US-licensed Prolia

• Registration Number: NCT04757376
• Lead Sponsor: Celltrion

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.

Study Timeline

• Study First Submitted: 2021-02-12
• Study First Submitted QC: 2021-02-12
• Study First Posted: 2021-02-17
• Study Start: 2021-06-17
• Primary Completion: 2023-05-18
• Study Completion: 2023-11-16
• Results First Submitted: 2024-04-19
• Results First Submitted QC: 2024-04-19
• Status Verified: 2024-05
• Results First Posted: 2024-05-16
• Last Update Submitted: 2024-05-20
• Last Update Posted: 2024-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 479

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CT-P41	CT-P41	60 mg/mL single dose administration, Solution for injection in prefilled syringe(PFS)
US-licensed Prolia	US-licensed Prolia	60 mg/mL single dose administration, Solution for injection in PFS

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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.
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 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 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.
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 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.
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.

Trial Locations

Locations (20)

AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Warszawie; 🇵🇱 Warszawa, Mazowieckie, Poland

East Tallinn Central Hospital-Ravi 18; 🇪🇪 Tallinn, Harjumaa, Estonia

Health Center 4-117 K. Barona Str; 🇱🇻 Riga, Latvia

NZOZ Osteo Medic SC Artur Racewicz Jerzy Supronik; 🇵🇱 Bialystok, Podlaskie, Poland

AES - AS - Medical Center of Medbud - Clinic LLC; 🇺🇦 Kyiv, Ukraine

MCM Krakow - PRATIA - PPDS; 🇵🇱 Kraków, Poland

Clinic of SI Institute of Gerontology n.a. D.F.Chebotaryov of NAMS of Ukraine; 🇺🇦 Kyiv, Ukraine

KLV Arstikabinet; 🇪🇪 Parnu, Estonia

Center For Clinical And Basic Research; 🇪🇪 Tallinn, Harjumaa, Estonia

Clinical Research Centre Ltd; 🇪🇪 Tartu, Tartumaa, Estonia

Health Center Association, Medical Center Liepaja; 🇱🇻 Liepaja, Latvia

SOMED CR Sp. z o.o. Sp. Komandytowa - Warszawa; 🇵🇱 Warszawa, Mazowieckie, Poland

SOMED CR Sp. z o.o. Sp. Komandytowa - Lodz; 🇵🇱 Lódz, Lódzkie, Poland

Krakowskie Centrum Medyczne; 🇵🇱 Kraków, Malopolskie, Poland

AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Gdyni; 🇵🇱 Gdynia, Pomorskie, Poland

AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu; 🇵🇱 Poznan, Wielkopolskie, Poland

Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov; 🇺🇦 Vinnytsia, Ukraine

Centrum Medyczne Poznan - PRATIA - PPDS; 🇵🇱 Skórzewo, Wielkopolskie, Poland

AES - AS - Medical Center of Edelweiss Medics LLC; 🇺🇦 Kyiv, Ukraine

AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu; 🇵🇱 Wroclaw, Dolnoslaskie, Poland