Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis

Phase 3

Completed

Conditions: Postmenopausal Women With Osteoporosis

Interventions: Biological: Bmab 1000
Biological: Prolia®

Registration Number: NCT05345691

Lead Sponsor: Biocon Biologics UK Ltd

Brief Summary: This is a randomized, double-blind, multicenter, parallel-arm, Phase 3 study to compare the efficacy, PK (Pharmacokinetic), PD (Pharmacodynamic), safety, and immunogenicity of Bmab 1000 and Prolia® in postmenopausal women with osteoporosis

Detailed Description: The study will consist of 3 study periods: Screening period; Part 1, double-blind active-controlled period; and Part 2, transition period. In the double-blind active-controlled period, eligible Patients will be randomized in a 1:1 ratio to receive either Bmab 1000 or Prolia®. Prior to dosing At Week 52, patients in Prolia® treatment group will be randomized again in a 1:1 ratio to either continue on Prolia® or be transitioned to Bmab 1000. To maintain the study blinding, the patients in the original Bmab 1000 arm will also go through the re-randomization procedure; however, they will continue to receive Bmab 1000. The interventions (Bmab 1000 or Prolia®) will be administered subcutaneously every 6 months. End-of-study visit will be at Week 78 post randomization (Month 18).

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 479

Inclusion Criteria

Postmenopausal women, aged ≥55 and <80 years at screening. Postmenopausal is defined as 12 months of spontaneous amenorrhea with serum FSH (follicle-stimulating hormone) levels ≥40 mIU/mL at screening or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
Evidence of osteoporosis as assessed by lumbar spine (L1-L4) absolute BMD corresponding to a T-score classification ≤-2.5 and ≥-4.0.
At least 3 vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA at screening.
Patients with body weight ≥50 to <90 kg at screening.

Exclusion Criteria

Patients with T-score of <-4.0 at the lumbar spine, total hip, or femoral neck.
Known history of previous exposure to denosumab (Prolia®, Xgeva®, or any biosimilar denosumab).
For prior or ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements) following points to be considered for the washout periods prior to the screening visit:

a. Oral bisphosphonate i. Ineligible if used for 3 or more years cumulatively ii. If used for <3 years, a gap of at least 1 year since the last dose is required at the screening visit b. Dose received any time
Systemic glucocorticosteroids
Patients with ongoing serious infections
Evidence of any of the following per the patient's history, DXA, or X-ray review and/or current disease:
1. Patient in bed rest for 2 or more weeks during the last 3 months prior to screening
2. Current hyperthyroidism or hypothyroidism
3. History and/or current hyperparathyroidism or hypoparathyroidism
4. Current hypocalcemia or hypercalcemia based on albumin-adjusted serum calcium
5. Any bone disease including bone metastasis or metabolic disease (except for osteoporosis), eg, osteomalacia or osteogenesis imperfecta, rheumatoid arthritis, Paget's disease, ALP (alkaline phosphatase) elevation (at investigator's discretion), Cushing's disease, clinically significant hyperprolactinemia (at investigator's discretion), fibrous dysplasia, malabsorption syndrome which may interfere with the interpretation of the results
6. History and/or presence of one severe or 3 or more moderate vertebral fractures
7. History and/or presence of hip fracture or bilateral hip replacement
8. Presence of an active healing fracture according to assessment of investigator
9. History of severe skeletal pain with bisphosphonates which, as per the investigator, is a risk to her participation in the trial
10. Oral/dental or periodontal conditions:

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bmab 1000	Bmab 1000	-
Prolia®:	Prolia®	-

Primary Outcome Measures

Name	Time	Method
Percentage Change in Lumbar Spine BMD (Bone Mineral Density)	Baseline and Week 52	To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 52 in lumbar spine BMD

Secondary Outcome Measures

Name	Time	Method
AUEC (Area Under the Effect Curve) of the Bone Resorption Marker sCTX (Serum C-terminal Telopeptide of Type 1 Collagen)	Baseline to Week 26	To demonstrate pharmacodynamic equivalence between Bmab 1000 and Prolia® based on AUEC of the bone resorption marker sCTX from baseline to week 26
Percentage Change in Lumbar Spine BMD	Baseline and Week 26	To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 26 in lumbar spine BMD
Percentage Change in Total Hip BMD by DXA (Dual-energy X-ray Absorptiometry)	Week 52	To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline, at Week 26 and Week 52 in lumbar spine BMD
Serum Concentrations of P1NP (Procollagen Type 1 N-terminal Propeptide)	Baseline up to Week 52	To compare bone turnover between Bmab 1000 and Prolia® based on P1NP after the first dose
Incidence of TEAEs (Treatment-emergent Adverse Events) up to 6 Months After the Second Dose	Baseline up to Week 78	To compare safety and tolerability of 2 administrations of Bmab 1000 and Prolia® 6 months apart
Incidence of ADA (Anti-drug Antibody)	Baseline up to Week 52 (Double-blind Active-controlled Period)	To compare immunogenicity between Bmab 1000 and Prolia®
Incidence of NAb (Neutralizing Antibody) up to Week 52	Week 78 (Transition Period)	To compare immunogenicity between Bmab 1000 and Prolia®
Percentage Change From Baseline in Hip BMD	Week 78	To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 78 in Hip BMD
Percentage Change From Baseline in Femoral BMD	Week 52	To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 52 in Femoral BMD
Minimum Concentration (Cmin) of sCTX	baseline to Week 26	To compare minimum Concentration (Cmin) of sCTX between Bmab 1000 and Prolia®
Denosumab Concentrations at Weeks 26	Weeks 26	Serum Concentrations of Denosumab
Denosumab Concentrations at Weeks 52	Weeks 52	Serum Concentrations of Denosumab
Denosumab Concentrations at Weeks 78	Weeks 78	Serum Concentrations of Denosumab

Trial Locations

Locations (1): PPD Global Ltd, Granta Park, Great Abington,
🇬🇧
Cambridge, UK, United Kingdom
PPD Global Ltd, Granta Park, Great Abington,
🇬🇧Cambridge, UK, United Kingdom