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
Overview
- Phase
- Phase 3
- Intervention
- Bmab 1000
- Conditions
- Postmenopausal Women With Osteoporosis
- Sponsor
- Biocon Biologics UK Ltd
- Enrollment
- 479
- Locations
- 1
- Primary Endpoint
- Percentage Change in Lumbar Spine BMD (Bone Mineral Density)
- Status
- Completed
- Last Updated
- 7 months ago
Overview
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).
Investigators
Eligibility Criteria
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.
- •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:
- •Patient in bed rest for 2 or more weeks during the last 3 months prior to screening
- •Current hyperthyroidism or hypothyroidism
- •History and/or current hyperparathyroidism or hypoparathyroidism
Arms & Interventions
Bmab 1000
Intervention: Bmab 1000
Prolia®:
Intervention: Prolia®
Outcomes
Primary Outcomes
Percentage Change in Lumbar Spine BMD (Bone Mineral Density)
Time Frame: 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 Outcomes
- AUEC (Area Under the Effect Curve) of the Bone Resorption Marker sCTX (Serum C-terminal Telopeptide of Type 1 Collagen)(Baseline to Week 26)
- Percentage Change in Lumbar Spine BMD(Baseline and Week 26)
- Percentage Change in Total Hip BMD by DXA (Dual-energy X-ray Absorptiometry)(Week 52)
- Serum Concentrations of P1NP (Procollagen Type 1 N-terminal Propeptide)(Baseline up to Week 52)
- Incidence of TEAEs (Treatment-emergent Adverse Events) up to 6 Months After the Second Dose(Baseline up to Week 78)
- Incidence of ADA (Anti-drug Antibody)(Baseline up to Week 52 (Double-blind Active-controlled Period))
- Incidence of NAb (Neutralizing Antibody) up to Week 52(Week 78 (Transition Period))
- Percentage Change From Baseline in Hip BMD(Week 78)
- Percentage Change From Baseline in Femoral BMD(Week 52)
- Minimum Concentration (Cmin) of sCTX(baseline to Week 26)
- Denosumab Concentrations at Weeks 26(Weeks 26)
- Denosumab Concentrations at Weeks 52(Weeks 52)
- Denosumab Concentrations at Weeks 78(Weeks 78)