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

A Randomized, Double-Blind, Multicenter, Parallel-Arm Phase 3 Study to Compare the Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis

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

Study Overview

• Status: Completed
• Conditions: Postmenopausal Women With Osteoporosis
• Intervention / Treatment: Biological: Bmab 1000; Biological: Prolia®

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).

• Study Type: Interventional
• Enrollment (Actual): 479
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • Cambridge, UK, United Kingdom, CB21 6GQ
      • PPD Global Ltd, Granta Park, Great Abington,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Evidence of osteoporosis as assessed by lumbar spine (L1-L4) absolute BMD corresponding to a T-score classification ≤-2.5 and ≥-4.0.
3. At least 3 vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA at screening.
4. Patients with body weight ≥50 to <90 kg at screening.

Exclusion Criteria:

1. Patients with T-score of <-4.0 at the lumbar spine, total hip, or femoral neck.
2. Known history of previous exposure to denosumab (Prolia®, Xgeva®, or any biosimilar denosumab).

3. 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

4. Systemic glucocorticosteroids
5. Patients with ongoing serious infections

6. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bmab 1000	Biological: Bmab 1000; 60 mg administered as a single SC (subcutaneous) injection once every 6 months.
Active Comparator: Prolia®:	Biological: Prolia®; 60 mg administered as a single SC injection once every 6 months

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Biocon Biologics UK Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2022
• Primary Completion (Actual): June 12, 2024
• Study Completion (Actual): June 12, 2024

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Denosumab
• Other Study ID Numbers: B1000-PMO-03-G-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No