Clinical trial NCT03974100: Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postmenopausal Women With Osteoporosis
Keywords: Prolia
GP2411
denosumab
postmenopausal osteoporosis
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
Collaborators: name: Hexal AG
First posted: 2019-06-04
Enrollment: 527
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set
timeFrame: Baseline (screening), up to Week 52
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set
timeFrame: Baseline (screening), up to Week 52
measure: Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set
timeFrame: Baseline (pre-dose Day 1), up to Week 26
measure: Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose
timeFrame: Baseline (pre-dose Day 1), up to Week 26
measure: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose
timeFrame: Baseline (pre-dose Day 1), up to Week 26
Secondary outcomes:
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set)
timeFrame: Baseline (screening), Week 26
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set)
timeFrame: Baseline (screening), Week 26
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
timeFrame: Baseline (screening), Week 78
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
timeFrame: Baseline (screening), Week 26 and Week 52
measure: 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)
timeFrame: Baseline (screening), Week 26 and Week 52
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
timeFrame: Baseline (screening), Week 78
measure: Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)
timeFrame: Baseline (screening), Week 26 and Week 52
measure: 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)
timeFrame: Baseline (screening), Week 26 and Week 52
measure: Percent Change From Baseline in Total Hip Bone Mineral Density (TH-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)
timeFrame: Baseline (screening), Week 78
measure: CTX Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
timeFrame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
measure: CTX Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
timeFrame: Week 56, Week 65 and Week 78
measure: PINP Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
timeFrame: Baseline (pre-dose Day 1), Day 2, Day 4, Week 8, Week 18, Week 22, Week 26, Week 39 and Week 52
measure: PINP Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
timeFrame: Week 56, Week 65 and Week 78
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs up to Week 52 - Treatment Period 1
timeFrame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs From Week 52 up to Week 78 - Treatment Period 2
timeFrame: From dosing of study treatment at Week 52 up to Week 78
measure: Number of Participants With Vertebral Fractures up to Week 52 - Treatment Period 1
timeFrame: Baseline (screening) and Week 52
measure: Number of Participants With Vertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
timeFrame: Week 52 and Week 78
measure: Number of Participants With Nonvertebral Fractures up to Week 52 - Treatment Period 1
timeFrame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
measure: Number of Participants With Nonvertebral Fractures From Week 52 up to Week 78 - Treatment Period 2
timeFrame: From dosing of study treatment at Week 52 up to Week 78
measure: Number of Participants With Injection Site Reactions (ISRs) up to Week 52 - Treatment Period 1
timeFrame: From first dose of study treatment on Day 1 up to pre-dose at Week 52
measure: Number of Participants With Injection Site Reactions (ISRs) From Week 52 up to Week 78 - Treatment Period 2
timeFrame: From dosing of study treatment at Week 52 up to Week 78
measure: Number of Participants With Anti-drug Antibodies (ADA) up to Week 52 - Treatment Period 1
timeFrame: From Week 2 up to Week 52
measure: Number of Participants With Anti-drug Antibodies (ADA) From Week 52 up to Week 78 - Treatment Period 2
timeFrame: From Week 56 up to Week 78
measure: Denosumab Serum Concentrations as Per Visit Schedule up to Week 52 - Treatment Period 1
timeFrame: 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
measure: Denosumab Serum Concentrations as Per Visit Schedule From Week 52 up to Week 78 - Treatment Period 2
timeFrame: Week 56, Week 65 and Week 78
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Sandoz Investigational Site
state: Arizona
city: Miami
country: United States
facility: Sandoz Investigational Site
state: Florida
city: Wichita
country: United States
facility: Sandoz Investigational Site
state: Kansas
city: Duncansville
country: United States
facility: Sandoz Investigational Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Sandoz Investigational Site
state: Pennsylvania
city: Carrollton
country: United States
facility: Sandoz Investigational Site
state: Texas
city: Plovdiv
country: Bulgaria
facility: Sandoz Investigational Site
city: Plovdiv
country: Bulgaria
facility: Sandoz Investigational Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigational Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigational Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigational Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigational Site
city: Ostrava
country: Czechia
facility: Sandoz Investigational Site
state: Czech Republic
city: Hradec Kralove
country: Czechia
facility: Sandoz Investigational Site
state: CZE
city: Brno
country: Czechia
facility: Sandoz Investigational Site
city: Ostrava
country: Czechia
facility: Sandoz Investigational Site
city: Pardubice
country: Czechia
facility: Sandoz Investigational Site
city: Plzen
country: Czechia
facility: Sandoz Investigational Site
city: Praha 11
country: Czechia
facility: Sandoz Investigational Site
city: Praha 2
country: Czechia
facility: Sandoz Investigational Site
city: Uherske Hradiste
country: Czechia
facility: Sandoz Investigational Site
city: Fujimi
country: Japan
facility: Sandoz Investigational Site
state: Saitama
city: Chuoh-ku
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Hachioji-city
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Kiyose-city
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Shinagawa
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Krakow
country: Poland
facility: Sandoz Investigational Site
state: Malopolskie
city: Bialystok
country: Poland
facility: Sandoz Investigational Site
city: Bialystok
country: Poland
facility: Sandoz Investigational Site
city: Bydgoszcz
country: Poland
facility: Sandoz Investigational Site
city: Lodz
country: Poland
facility: Sandoz Investigational Site
city: Nadarzyn
country: Poland
facility: Sandoz Investigational Site
city: Torun
country: Poland
facility: Sandoz Investigational Site
city: Warszawa
country: Poland
facility: Sandoz Investigational Site
city: Warszawa
country: Poland
facility: Sandoz Investigational Site
city: Warszawa
country: Poland
facility: Sandoz Investigational Site
city: Santiago de Compostela
country: Spain
facility: Sandoz Investigational Site
state: A Coruna
city: Sabadell
country: Spain
facility: Sandoz Investigational Site
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Sandoz Investigational Site
state: Galicia
city: Barcelona
country: Spain
facility: Sandoz Investigational Site
city: Madrid
country: Spain
facility: Sandoz Investigational Site
city: Sevilla
country: Spain
facility: Sandoz Investigational Site
Study officials:
References: