Study Investigating PK, PD, Efficacy, Safety, and Immunogenicity of Biosimilar Denosumab (GP2411) in Patients With Postmenopausal Osteoporosis

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)

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).

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.

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