Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis (DEVOTE)
Primary Purpose
Postmenopausal Women With Osteoporosis
Status
Active
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Bmab 1000
Prolia®
Sponsored by
About this trial
This is an interventional treatment trial for Postmenopausal Women With Osteoporosis
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 ≥-4.0.
- 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:
- 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
- Current hypocalcemia or hypercalcemia based on albumin-adjusted serum calcium
- 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
- History and/or presence of one severe or 3 or more moderate vertebral fractures
- History and/or presence of hip fracture or bilateral hip replacement
- Presence of an active healing fracture according to assessment of investigator
- History of severe skeletal pain with bisphosphonates which, as per the investigator, is a risk to her participation in the trial
- Oral/dental or periodontal conditions:
Sites / Locations
- PPD Global Ltd, Granta Park, Great Abington,
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Bmab 1000
Prolia®:
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Percentage change in total hip BMD by DXA (Dual-energy X-ray absorptiometry)
o 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)
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
To compare safety and tolerability of 2 administrations of Bmab 1000 and Prolia® 6 months apart
Titer of ADA (Anti-drug antibody)
To compare immunogenicity between Bmab 1000 and Prolia®
Incidence of ADA (Anti-drug antibody)
To compare immunogenicity between Bmab 1000 and Prolia®
Incidence of NAb (Neutralizing antibody) up to Week 52
To compare immunogenicity between Bmab 1000 and Prolia®
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05345691
Brief Title
Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis
Acronym
DEVOTE
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 24, 2022 (Actual)
Primary Completion Date
June 20, 2024 (Anticipated)
Study Completion Date
June 20, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocon Biologics UK Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Women With Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blind (Patient, Investigator)
Allocation
Randomized
Enrollment
480 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bmab 1000
Arm Type
Experimental
Arm Title
Prolia®:
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Bmab 1000
Intervention Description
60 mg administered as a single SC (subcutaneous) injection once every 6 months.
Intervention Type
Biological
Intervention Name(s)
Prolia®
Intervention Description
60 mg administered as a single SC injection once every 6 months
Primary Outcome Measure Information:
Title
Percentage change in lumbar spine BMD (Bone mineral density)
Description
To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 52 in lumbar spine BMD
Time Frame
Baseline and Week 52
Secondary Outcome Measure Information:
Title
AUEC (Area under the effect curve) of the bone resorption marker sCTX (serum C-terminal telopeptide of Type 1 collagen)
Description
To demonstrate pharmacodynamic equivalence between Bmab 1000 and Prolia® based on AUEC of the bone resorption marker sCTX from baseline to week 26
Time Frame
Baseline to Week 26
Title
Percentage change in lumbar spine BMD
Description
To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 26 in lumbar spine BMD
Time Frame
Baseline and Week 26
Title
Percentage change in total hip BMD by DXA (Dual-energy X-ray absorptiometry)
Description
o demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline, at Week 26 and Week 52 in lumbar spine BMD
Time Frame
Baseline, at Week 26 and Week 52
Title
Serum concentrations of P1NP (Procollagen Type 1 N-terminal propeptide)
Description
To compare bone turnover between Bmab 1000 and Prolia® based on P1NP after the first dose
Time Frame
Baseline up to Week 52
Title
Incidence of TEAEs (Treatment-emergent adverse events) up to 6 months after the second dose
Description
To compare safety and tolerability of 2 administrations of Bmab 1000 and Prolia® 6 months apart
Time Frame
Baseline up to Week 52
Title
Titer of ADA (Anti-drug antibody)
Description
To compare immunogenicity between Bmab 1000 and Prolia®
Time Frame
Baseline up to Week 52
Title
Incidence of ADA (Anti-drug antibody)
Description
To compare immunogenicity between Bmab 1000 and Prolia®
Time Frame
Baseline up to Week 52
Title
Incidence of NAb (Neutralizing antibody) up to Week 52
Description
To compare immunogenicity between Bmab 1000 and Prolia®
Time Frame
Baseline up to Week 52
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Postmenopausal women
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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 ≥-4.0.
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:
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
Current hypocalcemia or hypercalcemia based on albumin-adjusted serum calcium
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
History and/or presence of one severe or 3 or more moderate vertebral fractures
History and/or presence of hip fracture or bilateral hip replacement
Presence of an active healing fracture according to assessment of investigator
History of severe skeletal pain with bisphosphonates which, as per the investigator, is a risk to her participation in the trial
Oral/dental or periodontal conditions:
Facility Information:
Facility Name
PPD Global Ltd, Granta Park, Great Abington,
City
Cambridge
State/Province
UK
ZIP/Postal Code
CB21 6GQ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis
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