The primary objective of this study is to demonstrate equivalent efficacy of the proposed biosimilar denosumab FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
553
subcutaneously by single-use prefilled syringe (PFS)
subcutaneously by single-use PFS
Percentage Change From Baseline in LS-BMD by DXA
Bone density was measured at the lumbar spine from L1 through L4. Per FDA request for this study, data were analyzed by non-inferiority and non-superiority analyses. Decreased BMD is associated with risk of fracture.
Time frame: Baseline and Week 52
Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
Area under the effect curve for the (untransformed) biomarker concentrations from baseline up to Week 26. Any possible rebound effect where biomarker concentrations rose above baseline was not taken into account, and only the area below baseline was considered in this parameter.
Time frame: Baseline to Week 26
Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA
The proximal femur (inclusive of femoral neck and total hip) DXA scans were obtained from the left side when possible. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it had to be used consistently throughout the study. Data reported are for one half of the body only.
Time frame: Baseline and Week 52
Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
P1NP is a bone biomarker. Serum samples were collected for analysis of P1NP to evaluate bone formation (P1NP) in response to treatment with FKS518 and US-Prolia. A decrease in the serum levels of P1NP is expected following treatment with denosumab and is suggestive of improvement.
Time frame: Baseline and Week 52 pre dose
Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
Serum CTX is a bone biomarker. Serum samples were collected for analysis of CTX to evaluate bone resorption in response to treatment with FKS518 or US-Prolia. A decrease in the serum levels of CTX is expected following treatment with US-Prolia and is suggestive of improvement.
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Diagnostic Consultative Center Aleksandrovska
Sofia, Sofia-Grad, Bulgaria
Diagnostic Consultative Center (DCC) 17 - Sofia
Sofia, Sofia-Grad, Bulgaria
Medical Center N. I. Pirogov
Sofia, Sofia-Grad, Bulgaria
Medical Center Hipokrat 2000 OOD
Haskovo, Bulgaria
Medical Center Medconsult Pleven
Pleven, Bulgaria
Palmed University Multidisciplinary Hospital for Active Treatment
Plovdiv, Bulgaria
University Multi-profile Hospital for Active Treatment - Plovdiv
Plovdiv, Bulgaria
Medical Center - Teodora EOOD
Rousse, Bulgaria
Multiprofile Hospital for Active Treatment Hadzhi Dimitar
Sliven, Bulgaria
Lyulin Hospital
Sofia, Bulgaria
...and 66 more locations
Time frame: Baseline and Week 52 pre dose
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Treatment-emergence was defined as AEs that began or increased in severity or frequency on or after the date of first administration of IP in a given treatment Period (Core or Transition) up to the Early Termination/End of Study Visit.
Time frame: Day 1 to Week 78
Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE)
Treatment-emergence was defined as SAEs that began or increased in severity or frequency on or after the date of first administration of IP up to the Early Termination/End of Study Visit.
Time frame: Day 1 to Week 78
Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI)
A Treatment-emergent AESI is defined as drug-related hypersensitivity/allergic reactions (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≥3 or reported as serious adverse events \[SAEs\]) and AEs leading to IP discontinuation or study withdrawal.
Time frame: Day 1 to Week 78
Number of Participants Who Experienced an Injection Site Reaction (ISR)
Local tolerability in terms of ISRs was assessed by inspection of the skin and appendages in proximity to the site of administration. The injection site was the abdomen, and the IP was injected slowly. This local tolerability assessment was performed by the Investigator or designee to determine the presence of e.g., erythema, rash, tenderness, swelling, itching, bruising, pain, extravasation, phlebitis, or other types of reaction. The Investigator was also requested to ask participants during assessment about any such reactions that may have occurred since last assessment.
Time frame: Day 1 to Week 78