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

Postmenopausal Women With Osteoporosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04757376
• Other study ID #: CT-P41 3.1
• Secondary ID: 2020-005974-91
• Status: Completed
• Phase: Phase 3
• Start date: June 17, 2021
• Est. completion date: November 16, 2023

Study information

• Verified date: May 2024
• Source: Celltrion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 479
• Est. completion date: November 16, 2023
• Est. primary completion date: May 18, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Postmenopausal Women With Osteoporosis

Intervention

Biological:
• CT-P41
60 mg/mL single dose, Solution for injection in PFS
• US-licensed Prolia
60 mg/mL single dose, Solution for injection in PFS

Locations

Country	Name	City	State
Estonia	KLV Arstikabinet	Parnu
Estonia	Center For Clinical And Basic Research	Tallinn	Harjumaa
Estonia	East Tallinn Central Hospital-Ravi 18	Tallinn	Harjumaa
Estonia	Clinical Research Centre Ltd	Tartu	Tartumaa
Latvia	Health Center Association, Medical Center Liepaja	Liepaja
Latvia	Health Center 4-117 K. Barona Str	Riga
Poland	NZOZ Osteo Medic SC Artur Racewicz Jerzy Supronik	Bialystok	Podlaskie
Poland	AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Gdyni	Gdynia	Pomorskie
Poland	Krakowskie Centrum Medyczne	Kraków	Malopolskie
Poland	MCM Krakow - PRATIA - PPDS	Kraków
Poland	SOMED CR Sp. z o.o. Sp. Komandytowa - Lodz	Lódz	Lódzkie
Poland	AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu	Poznan	Wielkopolskie
Poland	Centrum Medyczne Poznan - PRATIA - PPDS	Skórzewo	Wielkopolskie
Poland	AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warszawa	Mazowieckie
Poland	SOMED CR Sp. z o.o. Sp. Komandytowa - Warszawa	Warszawa	Mazowieckie
Poland	AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu	Wroclaw	Dolnoslaskie
Ukraine	AES - AS - Medical Center of Edelweiss Medics LLC	Kyiv
Ukraine	AES - AS - Medical Center of Medbud - Clinic LLC	Kyiv
Ukraine	Clinic of SI Institute of Gerontology n.a. D.F.Chebotaryov of NAMS of Ukraine	Kyiv
Ukraine	Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov	Vinnytsia

Sponsors (1)

Lead Sponsor	Collaborator
Celltrion

Countries where clinical trial is conducted

Estonia,  Latvia,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	baseline (screening), Week 52 predose
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.	baseline (screening), Week 52 predose
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.	baseline (screening), Week 78
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.	up to Week 52 predose
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.	from Week 52 to Week 78
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.	Week 0 Day 1 predose, Week 26 predose
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.	Week 52
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.	from baseline (Week 0 Day 1 predose) to Week 26 predose
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.	Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
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.	Baseline (Week 0 Day 1 predose), Week 78
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.	Baseline (Week 0 Day 1 predose), Weeks 26 and 52 (predose)
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.	Baseline (Week 0 Day 1 predose), Week 78
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.	up to Week 52 predose
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.	from Week 52 to Week 78