A Randomized, Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of MAB-22 Versus Prolia® Sourced From the European Union in Postmenopausal Women With Osteoporosis
Overview
- Phase
- Phase 3
- Intervention
- MAB-22
- Conditions
- Osteoporosis
- Sponsor
- Xentria, Inc.
- Enrollment
- 440
- Primary Endpoint
- To compare MAB-22 and Prolia® (EU-authorized) in postmenopausal women with osteoporosis to demonstrate biosimilarity and non-inferiority with respect to Pharmacodynamic (PD) profile in terms of serum cross-linked C telopeptide of type I collagen (sCTX).
- Status
- Withdrawn
- Last Updated
- 11 months ago
Overview
Brief Summary
Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of MAB-22 Versus Prolia®
Detailed Description
A Randomized, Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of MAB-22 Versus Prolia® Sourced from the European Union in Postmenopausal Women with Osteoporosis
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent must be obtained before participation in the study.
- •Postmenopausal women diagnosed with osteoporosis (consistent with a lumbar spine bone mineral density (LS-BMD) \[L1-L4\] or TH-BMD T-score of ≤ -2.5 and ≥ -4.0 as measured by dual x-ray absorptiometry (DXA) at screening). Postmenopausal status is defined as at least 12 consecutive months of amenorrhea before date of screening, for which there is no other obvious pathological or physiological cause.
- •Between ≥55 and ≤80 years of age at screening.
- •Body weight ≥50 kg and ≤90 kg at screening.
- •At least 3 vertebrae in the L1-L4 region (vertebrae to be assessed by local reading of lateral spine x-ray at screening) and at least one hip joint are evaluable by DXA.
- •Adequate organ function as defined by the following criteria:
- •Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN).
- •Total serum bilirubin ≤1.5 × ULN.
- •Absolute neutrophil count ≥1500 cells/μL (SI units: ≥1.5 × 109/L).
- •Platelet count ≥100,000 cells/μL (SI units: ≥100 × 109/L) and ≤ULN.
Exclusion Criteria
- •Previous exposure to denosumab (Prolia®, Xgeva®, or biosimilar denosumab).
- •History of hypersensitivity to any recombinant protein drugs or any of the excipients used in MAB-22 or Prolia®.
- •History and/or presence of 1 severe or more than 2 moderate vertebral fractures or hip fractures (as determined by local reading of lateral spine x-ray at screening). Osteoporotic-related fracture (i.e., crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 6 months of randomization.
- •Recent long bone fracture (within 6 months) before screening. Presence of active healing fracture according to assessment of investigators.
- •History and/or presence of bone metastases, bone disease, or metabolic disease, other than osteoporosis, which could interfere with the interpretation of the findings (e.g., osteogenesis imperfecta, osteopetrosis, osteomalacia, rheumatoid arthritis, Paget's disease, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, malabsorption syndrome, hypoparathyroidism or hyperparathyroidism \[irrespective of current controlled or uncontrolled status\], hypocalcemia or hypercalcemia \[based on albumin-adjusted serum calcium\]).
- •Malignancy within the 5 years before screening (except cervical carcinoma in situ or basal cell carcinoma, which are acceptable).
- •Ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). The following rules for washout periods for osteoporosis treatments must be adhered to:
- •Drugs being investigated for osteoporosis (e.g., romosozumab): dose received at any time.
- •Strontium or fluoride (for osteoporosis): dose received at any time.
- •Tibolone, oral or transdermal estrogen, selective estrogen receptor modulators, systemic hormone replacement therapy: dose received within 12 months before screening.
Arms & Interventions
Prolia® and MAB-22
Single subcutaneous dose of Prolia® at Day 1 (baseline), 6 months (Week 26) and single subcutaneous dose of MAB-22 (switching) or Prolia ® (non-switching) at Visit 12 (Week 52)
Intervention: MAB-22
MAB-22
Single subcutaneous dose at Day 1 (baseline), 6 months (Week 26) and Visit 12 (Week 52)
Intervention: MAB-22
Prolia® and MAB-22
Single subcutaneous dose of Prolia® at Day 1 (baseline), 6 months (Week 26) and single subcutaneous dose of MAB-22 (switching) or Prolia ® (non-switching) at Visit 12 (Week 52)
Intervention: Prolia®
Outcomes
Primary Outcomes
To compare MAB-22 and Prolia® (EU-authorized) in postmenopausal women with osteoporosis to demonstrate biosimilarity and non-inferiority with respect to Pharmacodynamic (PD) profile in terms of serum cross-linked C telopeptide of type I collagen (sCTX).
Time Frame: Day 1 to Week 26 [Predose]
PD coprimary endpoint: area under the effect curve (AUEC) of C telopeptide of type I collagen (sCTX) over the initial 6-month period
To compare MAB-22 and Prolia® (EU-authorized) in postmenopausal women with osteoporosis to demonstrate biosimilarity and non-inferiority with respect to efficacy profile in terms of bone mineral density (BMD).
Time Frame: Day 1 to Week 52
Efficacy coprimary endpoint: percentage change from baseline (%CfB) in lumbar spine bone mineral density (BMD) (LS-BMD)