NCT03974100

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).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
527

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2019

Typical duration for phase_3

Geographic Reach
6 countries

42 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 3, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 4, 2019

Completed
28 days until next milestone

Study Start

First participant enrolled

July 2, 2019

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 22, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 22, 2022

Completed
11 months until next milestone

Results Posted

Study results publicly available

March 8, 2023

Completed
Last Updated

March 8, 2023

Status Verified

February 1, 2023

Enrollment Period

2.8 years

First QC Date

June 3, 2019

Results QC Date

February 7, 2023

Last Update Submit

February 7, 2023

Conditions

Postmenopausal Women With Osteoporosis

Keywords

ProliaGP2411denosumabpostmenopausal osteoporosis

Outcome Measures

Primary Outcomes (5)

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Per-Protocol Set

    Bone density measurements were performed by dual energy X-ray absorptiometry (DXA). Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Values at Week 52 were estimated from the model and are presented in the table.

    Baseline (screening), up to Week 52

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - TP1 Full Analysis Set

    Bone density measurements were performed by DXA. Lumbar spine scan included L1 through L4 vertebrae. All DXA scans were submitted to a central imaging vendor for analysis. A MMRM was fitted to the changes from baseline in LS-BMD for all post-baseline time points up to Week 52. Missing values were assumed to be missing at random (MAR) using the MMRM model. Values at Week 52 were estimated from the model and are presented in the table.

    Baseline (screening), up to Week 52

  • Area Under the Effect-time Curve (AUEC) of Percentage Change From Baseline in Serum CTX Concentrations After First Dose - Pharmacodynamic Analysis Set

    Carboxy-terminal crosslinked telopeptides of type I collagen (CTX) is a bone resorption biomarker. Serum CTX concentration-time data were analyzed by non-compartmental methods. The AUEC of baseline corrected serum CTX concentrations (% change from baseline) was calculated using the linear trapezoidal method. Values below the lower limit of quantification (LLOQ) were imputed with the actual value for the LLOQ.

    Baseline (pre-dose Day 1), up to Week 26

  • Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose

    Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero.

    Baseline (pre-dose Day 1), up to Week 26

  • Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Denosumab After First Dose

    Serum denosumab concentration-time data were analyzed by non-compartmental methods. Missing denosumab serum concentrations or concentrations below the LLOQ were not imputed and handled as missing values, except for the pre-dose sample which were treated as zero. The linear-up log-down trapezoidal method was used for the AUCinf calculation.

    Baseline (pre-dose Day 1), up to Week 26

Secondary Outcomes (25)

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (Per-Protocol Set)

    Baseline (screening), Week 26

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 26 - Treatment Period 1 (TP1 Full Analysis Set)

    Baseline (screening), Week 26

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 78 - Treatment Period 2 (TP2 Full Analysis Set)

    Baseline (screening), Week 78

  • Percent Change From Baseline in Femoral Neck Bone Mineral Density (FN-BMD) at Week 26 and Week 52 - Treatment Period 1 (Per-Protocol Set)

    Baseline (screening), Week 26 and Week 52

  • 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)

    Baseline (screening), Week 26 and Week 52

  • +20 more secondary outcomes

Study Arms (2)

GP2411

EXPERIMENTAL

60 mg /mL subcutaneous injection every 6 months

Biological: GP2411

EU authorized Prolia

ACTIVE COMPARATOR

60 mg /mL subcutaneous injection every 6 months

Biological: EU-Prolia (EU-authorized Prolia®)

Interventions

GP2411BIOLOGICAL

60 mg /mL subcutaneous injection every 6 months

GP2411
EU-Prolia (EU-authorized Prolia®)BIOLOGICAL

60 mg /mL subcutaneous injection every 6 months

EU authorized Prolia

Eligibility Criteria

Age55 Years - 80 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsPostmenopausal women, diagnosed with osteoporosis
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (42)

Sandoz Investigational Site

Peoria, Arizona, 85381, United States

Location

Sandoz Investigational Site

Miami, Florida, 33135, United States

Location

Sandoz Investigational Site

Wichita, Kansas, 67207, United States

Location

Sandoz Investigational Site

Duncansville, Pennsylvania, 16635, United States

Location

Sandoz Investigational Site

Wyomissing, Pennsylvania, 19610, United States

Location

Sandoz Investigational Site

Carrollton, Texas, 75010, United States

Location

Sandoz Investigational Site

Plovdiv, 4001, Bulgaria

Location

Sandoz Investigational Site

Plovdiv, 4002, Bulgaria

Location

Sandoz Investigational Site

Sofia, 1431, Bulgaria

Location

Sandoz Investigational Site

Sofia, 1505, Bulgaria

Location

Sandoz Investigational Site

Sofia, 1680, Bulgaria

Location

Sandoz Investigational Site

Sofia, 1784, Bulgaria

Location

Sandoz Investigational Site

Ostrava, Czech Republic, 772 00, Czechia

Location

Sandoz Investigational Site

Hradec Králové, CZE, 500 05, Czechia

Location

Sandoz Investigational Site

Brno, 602 00, Czechia

Location

Sandoz Investigational Site

Ostrava, 702 00, Czechia

Location

Sandoz Investigational Site

Pardubice, 530 02, Czechia

Location

Sandoz Investigational Site

Pilsen, 30460, Czechia

Location

Sandoz Investigational Site

Prague, 128 50, Czechia

Location

Sandoz Investigational Site

Prague, 14900, Czechia

Location

Sandoz Investigational Site

Uherské Hradiště, 686 01, Czechia

Location

Sandoz Investigational Site

Fujimi, Saitama, 354-0021, Japan

Location

Sandoz Investigational Site

Chuoh-ku, Tokyo, 104-0031, Japan

Location

Sandoz Investigational Site

Hachiōji, Tokyo, 192-0046, Japan

Location

Sandoz Investigational Site

Kiyose, Tokyo, 204-0021, Japan

Location

Sandoz Investigational Site

Shinagawa, Tokyo, 140-0014, Japan

Location

Sandoz Investigational Site

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Sandoz Investigational Site

Bialystok, 15-351, Poland

Location

Sandoz Investigational Site

Bialystok, 15-461, Poland

Location

Sandoz Investigational Site

Bydgoszcz, 85 168, Poland

Location

Sandoz Investigational Site

Lodz, 90 242, Poland

Location

Sandoz Investigational Site

Nadarzyn, 05-830, Poland

Location

Sandoz Investigational Site

Torun, 87-100, Poland

Location

Sandoz Investigational Site

Warsaw, 00-874, Poland

Location

Sandoz Investigational Site

Warsaw, 02 118, Poland

Location

Sandoz Investigational Site

Warsaw, 02 691, Poland

Location

Sandoz Investigational Site

Santiago de Compostela, A Coruna, 15705, Spain

Location

Sandoz Investigational Site

Sabadell, Barcelona, 08208, Spain

Location

Sandoz Investigational Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Sandoz Investigational Site

Barcelona, 08041, Spain

Location

Sandoz Investigational Site

Madrid, 28009, Spain

Location

Sandoz Investigational Site

Seville, 41010, Spain

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Condition Hierarchy (Ancestors)

OsteoporosisBone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
Novartis.email@novartis.com
862-778-8300

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
double blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 3, 2019

First Posted

June 4, 2019

Study Start

July 2, 2019

Primary Completion

April 22, 2022

Study Completion

April 22, 2022

Last Updated

March 8, 2023

Results First Posted

March 8, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Locations

ES(6)JP(5)PL(10)BU(6)US(6)CZ(9)