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

Celltrion479 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

479

Conditions

Postmenopausal Women With Osteoporosis

Interventions

CT-P41BIOLOGICAL

60 mg/mL single dose, Solution for injection in PFS

US-licensed ProliaBIOLOGICAL

60 mg/mL single dose, Solution for injection in PFS

Eligibility

Sex: FEMALEMin age: 50 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (20)

Center For Clinical And Basic Research

Tallinn, Harju, Estonia

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

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.

Data from ClinicalTrials.gov

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East Tallinn Central Hospital-Ravi 18

Tallinn, Harju, Estonia

Clinical Research Centre Ltd

Tartu, Tartu, Estonia

KLV Arstikabinet

Pärnu, Estonia

Health Center Association, Medical Center Liepaja

Liepāja, Latvia

Health Center 4-117 K. Barona Str

Riga, Latvia

AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Centrum Medyczne Poznan - PRATIA - PPDS

Skórzewo, Greater Poland Voivodeship, Poland

Krakowskie Centrum Medyczne

Krakow, Lesser Poland Voivodeship, Poland

AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

...and 10 more locations

Time frame: up to Week 52 predose

Incidence of New Vertebral, Nonvertebral, and Hip Fractures During TP II - FAS-TP II Subset

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: from Week 52 to Week 78