Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis (NCT NCT04934072)

Last Updated: 2025-02-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

553 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2025-02-27

Participant Flow

A total of 553 participants were randomized in the study at 64 centers across 6 countries (Bulgaria, Czech Republic, Estonia, Georgia, Hungary, and Poland) between June 2021 and January 2022.

The study included a Screening Period of maximum 28 days prior to first drug (FKS518 and US-Prolia) administration, a double-blind Core Treatment Period up to Week 52, and a double-blind single Transition Period from Week 52 up to Week 78, with administration of the study drug on Day 1, Week 26, and Week 52.

Participant milestones

Participant milestones
Measure	Core Treatment Period FKS518 Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Transition Period: FKS518 (Was on FKS518 in CTP) Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Period: FKS518 (Switched From US-Prolia in CTP) Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Period: US-Prolia (Was on US-Prolia in CTP) Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Day 0 to Week 52 STARTED	277	276	0	0	0
Day 0 to Week 52 COMPLETED	252	249	0	0	0
Day 0 to Week 52 NOT COMPLETED	25	27	0	0	0
Week 52 to Week 78 STARTED	0	0	252	124	125
Week 52 to Week 78 COMPLETED	0	0	245	122	122
Week 52 to Week 78 NOT COMPLETED	0	0	7	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Core Treatment Period FKS518 Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Transition Period: FKS518 (Was on FKS518 in CTP) Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Period: FKS518 (Switched From US-Prolia in CTP) Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Period: US-Prolia (Was on US-Prolia in CTP) Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Day 0 to Week 52 Withdrawal by Subject	17	22	0	0	0
Day 0 to Week 52 Discontinued Treatment Prior to Week 52	4	1	0	0	0
Day 0 to Week 52 Other	3	1	0	0	0
Day 0 to Week 52 Adverse Event	1	3	0	0	0
Week 52 to Week 78 Adverse Event	0	0	0	1	1
Week 52 to Week 78 Withdrawal by Subject	0	0	6	1	2
Week 52 to Week 78 Other	0	0	1	0	0

Baseline Characteristics

A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FKS518 n=277 Participants FKS518: Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	US-Prolia n=276 Participants US-Prolia: Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Total n=553 Participants Total of all reporting groups
Age, Continuous	65.2 Years STANDARD_DEVIATION 6.44 • n=5 Participants	65.8 Years STANDARD_DEVIATION 6.47 • n=7 Participants	65.5 Years STANDARD_DEVIATION 6.46 • n=5 Participants
Sex: Female, Male Female	277 Participants n=5 Participants	276 Participants n=7 Participants	553 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	277 Participants n=5 Participants	276 Participants n=7 Participants	553 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Lumbar spine bone mineral density (LS-BMD) by dual energy X-ray absorptiometry (DXA)	0.7872 g/cm^2 STANDARD_DEVIATION 0.06381 • n=5 Participants	0.7929 g/cm^2 STANDARD_DEVIATION 0.05962 • n=7 Participants	0.7901 g/cm^2 STANDARD_DEVIATION 0.06176 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Percentage Change From Baseline in LS-BMD by DXA Non-Inferiority Analysis	—	—	—	5.52 Percentage change Standard Error 0.292	5.07 Percentage change Standard Error 0.297	—	—	—
Percentage Change From Baseline in LS-BMD by DXA Non-Superiority Analysis	—	—	—	5.73 Percentage change Standard Error 0.292	5.03 Percentage change Standard Error 0.297	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	—	—	—	1884 (ng*h/L) Interval 1840.0 to 1928.0	1862 (ng*h/L) Interval 1818.0 to 1908.0	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA BMD at Femoral Neck at Week 52	—	—	—	2.07 Percentage change Standard Error 0.284	1.85 Percentage change Standard Error 0.291	—	—	—
Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA BMD at Total Hip at Week 52	—	—	—	2.97 Percentage change Standard Error 0.217	2.88 Percentage change Standard Error 0.223	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 52 pre dose

Population: Pharmacodynamic (PD) Analysis Set: All participants who received at least 1 dose of investigational product, had a quantifiable baseline PD marker concentration, and enough samples not impacted by protocol deviations to calculate the PD parameter. Only participants with available data are included.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=236 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=237 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)	—	—	—	-65.27 Percentage change Standard Error 2.491	-63.25 Percentage change Standard Error 2.536	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 52 pre dose

Population: PD Analysis Set: All participants who received at least 1 dose of investigational product, had a quantifiable baseline PD marker concentration, and enough samples not impacted by protocol deviations to calculate the PD parameter. Only participants with available data are included.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=236 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=235 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	—	—	—	-68.16 Percentage Change Standard Error 4.241	-64.47 Percentage Change Standard Error 4.330	—	—	—

SECONDARY outcome

Timeframe: Day 1 to Week 78

Population: Safety Analysis Set (SAF): The SAF included all participants who received at least 1 dose of IP. The Transition Period Safety Analysis (TP-SAF) Set included all participants who received at least 1 dose of IP during the course of the TP. Participants were analyzed according to the actual treatment they received.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia n=152 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 n=252 Participants Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia n=125 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	202 Participants	102 Participants	103 Participants	185 Participants	189 Participants	106 Participants	58 Participants	47 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 78

Population: SAF: SAF included all participants who received at least 1 dose of IP. The TP-SAF Set included all participants who received at least 1 dose of IP during the course of the TP. Participants were analyzed according to the actual treatment they received.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia n=152 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 n=252 Participants Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia n=125 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE)	50 Participants	27 Participants	33 Participants	43 Participants	50 Participants	8 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 78

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia n=152 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 n=252 Participants Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia n=125 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI)	0 Participants	1 Participants	7 Participants	0 Participants	7 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 78

Population: SAF: The SAF included all participants who received at least 1 dose of IP. The TP-SAF Set included all participants who received at least 1 dose of IP during the course of the TP. Participants were analyzed according to the actual treatment they received.

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.

Outcome measures

Outcome measures
Measure	Overall Period: FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously, every 26 weeks during the Core Treatment Period (Baseline to Week 52) and then continued to receive FKS518 treatment 60 mg subcutaneously, every 26 weeks during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants who were originally randomized to receive US-Prolia during core treatment period (Baseline to Week 52) were re-randomized to receive FKS518 subcutaneously; 60 mg every 26 weeks during transition treatment period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Overall Period: US-Prolia n=152 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78). This Reporting Group is used to report the results of the Overall period (Baseline to Week 78).	Core Treatment Period FKS518 n=277 Participants Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period US-Prolia n=276 Participants Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: FKS518; Transition Period: FKS518 n=252 Participants Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: FKS518 n=124 Participants Participants treated with US-Prolia during Core period were re-randomised to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Core Treatment Period: US-Prolia; Transition Period: US-Prolia n=125 Participants Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Number of Participants Who Experienced an Injection Site Reaction (ISR)	2 Participants	1 Participants	2 Participants	1 Participants	2 Participants	1 Participants	0 Participants	1 Participants

Adverse Events

Core Treatment Period: FKS518

Serious events: 43 serious events

Other events: 69 other events

Deaths: 0 deaths

Core Treatment Period: US-Prolia

Serious events: 50 serious events

Other events: 78 other events

Deaths: 0 deaths

Transition Treatment Period: FKS518 (Was on FKS518 in CTP)

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Transition Treatment Period: US-Prolia (Was on US-Prolia in CTP)

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Transition Treatment Period: FKS518 (Switched From US-Prolia in CTP)

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Core Treatment Period: FKS518 n=277 participants at risk Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: US-Prolia n=276 participants at risk Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Transition Treatment Period: FKS518 (Was on FKS518 in CTP) n=252 participants at risk Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Treatment Period: US-Prolia (Was on US-Prolia in CTP) n=125 participants at risk Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Treatment Period: FKS518 (Switched From US-Prolia in CTP) n=124 participants at risk Participants treated with US-Prolia during Core period were re-randomized to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Infections and infestations COVID-19	11.6% 32/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	14.9% 41/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	2.4% 6/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	2.4% 3/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	3.2% 4/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Infections and infestations Asymptomatic COVID-19	1.1% 3/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Infections and infestations COVID-19 pneumonia	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer recurrent	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.81% 1/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasopharyngeal cancer	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour of the lung metastatic	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral papilloma	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Balance disorder	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Chronic inflammatory demyelinating polyradiculoneuropathy	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.80% 1/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Dizziness	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.80% 1/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Loss of consciousness	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Musculoskeletal and connective tissue disorders Foot deformity	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.80% 1/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Reproductive system and breast disorders Hydrometra	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Reproductive system and breast disorders Rectocele	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.40% 1/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Cardiac disorders Angina pectoris	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.40% 1/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Ear and labyrinth disorders Vestibular disorder	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.81% 1/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Product Issues Device dislocation	0.00% 0/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.36% 1/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Asthma	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Vascular disorders Hypertension	0.36% 1/277 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/276 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.

Other adverse events

Other adverse events
Measure	Core Treatment Period: FKS518 n=277 participants at risk Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Core Treatment Period: US-Prolia n=276 participants at risk Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52).	Transition Treatment Period: FKS518 (Was on FKS518 in CTP) n=252 participants at risk Participants treated with FKS518 during Core Treatment Period received FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Treatment Period: US-Prolia (Was on US-Prolia in CTP) n=125 participants at risk Participants treated with US-Prolia during Core period were continued to receive US-Prolia 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).	Transition Treatment Period: FKS518 (Switched From US-Prolia in CTP) n=124 participants at risk Participants treated with US-Prolia during Core period were re-randomized to receive FKS518 60 mg subcutaneously on Week 52 during the Transition Period (Week 52 to Week 78).
Infections and infestations Nasopharyngitis	9.4% 26/277 • Number of events 33 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	12.0% 33/276 • Number of events 41 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	4.4% 11/252 • Number of events 12 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	6.4% 8/125 • Number of events 8 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	13.7% 17/124 • Number of events 18 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Infections and infestations Upper respiratory tract infection	8.3% 23/277 • Number of events 29 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	10.9% 30/276 • Number of events 36 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	4.8% 12/252 • Number of events 14 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	5.6% 7/125 • Number of events 7 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	6.5% 8/124 • Number of events 8 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Infections and infestations Urinary tract infection	6.5% 18/277 • Number of events 22 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	8.3% 23/276 • Number of events 28 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Headache	4.7% 13/277 • Number of events 14 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	5.1% 14/276 • Number of events 15 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/252 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/125 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.	0.00% 0/124 • Day 1 up to Week 78 The SAF included all participants who received at least 1 dose of IP. All adverse events occurring in the Core Period and Transition Period are presented. Participants were analyzed according to the actual treatment they received.

Additional Information

Clinical Development

Fresenius Kabi SwissBioSim GmbH

Phone: +41 793075735

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place