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

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

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

Study Overview

• Status: Completed
• Conditions: Postmenopausal Women With Osteoporosis
• Intervention / Treatment: Biological: CT-P41; Biological: US-licensed Prolia

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 Type: Interventional
• Enrollment (Actual): 479
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Parnu, Estonia, 80010
    • KLV Arstikabinet
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10128
      • Center for Clinical and Basic Research
    • Tallinn, Harjumaa, Estonia, 11312
      • East Tallinn Central Hospital-Ravi 18
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50106
      • Clinical Research Centre Ltd
• Latvia
  • Liepaja, Latvia, 3401
    • Health Center Association, Medical Center Liepaja
  • Riga, Latvia, 1012
    • Health Center 4-117 K. Barona Str
• Poland
  • Kraków, Poland, 30-510
    • MCM Krakow - PRATIA - PPDS
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-381
      • AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
  • Lódzkie
    • Lódz, Lódzkie, Poland, 90-368
      • SOMED CR Sp. z o.o. Sp. Komandytowa - Lodz
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-501
      • Krakowskie Centrum Medyczne
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-192
      • AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Warszawie
    • Warszawa, Mazowieckie, Poland, 01-737
      • SOMED CR Sp. z o.o. Sp. Komandytowa - Warszawa
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-351
      • NZOZ Osteo Medic SC Artur Racewicz Jerzy Supronik
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-537
      • AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Gdyni
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-702
      • AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu
    • Skórzewo, Wielkopolskie, Poland, 60-185
      • Centrum Medyczne Poznan - PRATIA - PPDS
• Ukraine
  • Kyiv, Ukraine, 02002
    • AES - AS - Medical Center of Edelweiss Medics LLC
  • Kyiv, Ukraine, 04114
    • Clinic of SI Institute of Gerontology n.a. D.F.Chebotaryov of NAMS of Ukraine
  • Kyiv, Ukraine
    • AES - AS - Medical Center of Medbud - Clinic LLC
  • Vinnytsia, Ukraine, 21029
    • Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT-P41; 60 mg/mL single dose administration, Solution for injection in prefilled syringe(PFS)	Biological: CT-P41; 60 mg/mL single dose, Solution for injection in PFS
Active Comparator: US-licensed Prolia; 60 mg/mL single dose administration, Solution for injection in PFS	Biological: US-licensed Prolia; 60 mg/mL single dose, Solution for injection in PFS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	baseline (screening), Week 52 predose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline (screening), Week 52 predose
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.	baseline (screening), Week 78
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.	up to Week 52 predose
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.	from Week 52 to Week 78
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.	Week 0 Day 1 predose, Week 26 predose
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.	Week 52
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.	from baseline (Week 0 Day 1 predose) to Week 26 predose
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.	Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
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.	Baseline (Week 0 Day 1 predose), Week 78
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.	Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
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.	Baseline (Week 0 Day 1 predose), 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	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.	up to Week 52 predose
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.	from Week 52 to Week 78

Collaborators and Investigators

• Sponsor: Celltrion

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): November 16, 2023

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: CT-P41 3.1; 2020-005974-91 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No