Postmenopausal Osteoporosis
Conditions
Keywords
Postmenopausal Osteoporosis, FKS518, Denosumab, US-licensed Prolia
Brief summary
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).
Interventions
DRUGFKS518
subcutaneously by single-use prefilled syringe (PFS)
DRUGUS-licensed Prolia (Amgen)
subcutaneously by single-use PFS
Sponsors
Fresenius Kabi SwissBioSim GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Female ≥55 to ≤85 years of age, inclusive, at screening. 2. Have a body mass index (BMI) ≥18 to ≤32 kg/m\^2. 3. Participant should have confirmed postmenopausal status, defined as age-related or early/premature amenorrhea ≥12 consecutive months and increased follicle-stimulating hormone (FSH) \>40 mIU/mL at screening; or surgical menopause (bilateral oophorectomy with or without hysterectomy) ≥12 months prior to screening. 4. Absolute bone mineral density (BMD) consistent with T-score ≤-2.5 and ≥-4.0 at the lumbar spine as measured by dual energy x-ray absorptiometry (DXA) as per central assessment. 5. At least 2 vertebrae in the lumbar vertebrae 1 to lumbar vertebrae 4 (L1-L4) region and at least 1 hip joint are evaluable by DXA. 6. Clinically acceptable physical examinations and laboratory tests and no history or evidence of any clinically significant concomitant medical disorder that, in the opinion of the Investigator, would pose a risk to participant safety or interfere with study evaluations or procedures. 7. Written informed consent including accepting a separate Information Sheet containing important information about COVID-19 and its general risks for participants participating in the clinical trial.
Exclusion criteria
Disease-related 1. History and/or presence of 1 severe or \>2 moderate vertebral fractures or hip fracture confirmed by x-ray. 2. Presence of active healing fracture at screening. 3. History and/or presence of bone-related disorders, such as but not limited to Paget's disease, osteomalacia, hyperparathyroidism (or parathyroid disorders), or renal osteodystrophy. 4. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, or oral surgery in the past 6 months), poor oral hygiene, periodontal, and/or pre-existing dental disease as assessed by the Investigator. 5. Evidence of hypocalcemia (albumin-adjusted serum calcium \<2.13 mmol/L or \<8.5 mg/dL) or hypercalcemia (albumin-adjusted serum calcium \>2.6 mmol/L or \>10.5 mg/dL) as assessed by the central laboratory at screening. 6. Vitamin D deficiency (25-hydroxy vitamin D levels \<12 ng/mL) as assessed by central laboratory at screening (retest is allowed once). 7. Known intolerance to calcium or vitamin D supplements. Other Medical Conditions 8. Known or suspected clinically relevant drug hypersensitivity to any components of the study drug, comparable drugs, or to latex. 9. Renal impairment: creatinine clearance \<30 mL/min at screening or receiving dialysis. 10. Medical evidence of current or history of primary or secondary immunodeficiency. 11. Infection-related exclusions as further defined in the protocol. 12. Major surgical procedure within 8 weeks prior to the screening or scheduled during the study. 13. Current or history of any malignancy, or myeloproliferative, or lymphoproliferative disease within 5 years before screening. 14. History of clinically significant drug or alcohol abuse within the last year prior to randomization. 15. Prior denosumab (Prolia, Xgeva, or proposed denosumab biosimilar) exposure. 16. Prior use of fluoride within the 5 years before inclusion in the study. 17. Any current or prior use of strontium ranelate. 18. Any current or prior use of intravenous bisphosphonates. 19. Current or prior use of teriparatide and other parathormone (PTH) analogues within 12 months before screening. 20. Current or prior use of systemic oral or transdermal estrogen or selective estrogen receptor modulators or tibolone within 6 months before screening. 21. Current or prior use of calcitonin or cinacalcet within 3 months before screening or any cathepsin K inhibitor (eg, odanacatib) within 18 months before screening. 22. Current or prior use of romosozumab or antisclerostin antibody. 23. Current or prior use of other osteoporotic agents used for the prevention or treatment of osteoporosis. 24. Current use within 3 months before screening of any medication with known influence on the skeletal system (eg, systemic corticosteroids, heparin, lithium, etc) with exceptions described in the protocol. 25. Concomitant treatment with another biologic drug. 26. Have received a COVID-19 vaccine within 4 weeks before randomization or COVID-19 vaccination is ongoing at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in LS-BMD by DXA | Baseline and Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA | Baseline and Week 52 | 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. |
| Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Baseline and Week 52 pre dose | 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. |
| Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | Baseline and Week 52 pre dose | 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. |
| Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | Baseline to Week 26 | 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. |
| Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | Day 1 to Week 78 | 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. |
| Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 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. |
| Number of Participants Who Experienced an Injection Site Reaction (ISR) | Day 1 to Week 78 | 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. |
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to Week 78 | 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. |
Countries
Bulgaria, Czechia, Estonia, Georgia, Hungary, Poland
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| FKS518 FKS518: Participants received FKS518 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52). | 277 |
| US-Prolia US-Prolia: Participants received US-Prolia 60 mg subcutaneously on Day 1 and Week 26 during the Core Treatment Period (Baseline to Week 52). | 276 |
| Total | 553 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Day 0 to Week 52 | Adverse Event | 1 | 3 | 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 | Withdrawal by Subject | 17 | 22 | 0 | 0 | 0 |
| Week 52 to Week 78 | Adverse Event | 0 | 0 | 0 | 1 | 1 |
| Week 52 to Week 78 | Other | 0 | 0 | 1 | 0 | 0 |
| Week 52 to Week 78 | Withdrawal by Subject | 0 | 0 | 6 | 1 | 2 |
Baseline characteristics
| Characteristic | FKS518 | US-Prolia | Total |
|---|---|---|---|
| Age, Continuous | 65.2 Years STANDARD_DEVIATION 6.44 | 65.8 Years STANDARD_DEVIATION 6.47 | 65.5 Years STANDARD_DEVIATION 6.46 |
| Lumbar spine bone mineral density (LS-BMD) by dual energy X-ray absorptiometry (DXA) | 0.7872 g/cm^2 STANDARD_DEVIATION 0.06381 | 0.7929 g/cm^2 STANDARD_DEVIATION 0.05962 | 0.7901 g/cm^2 STANDARD_DEVIATION 0.06176 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 277 Participants | 276 Participants | 553 Participants |
| Sex: Female, Male Female | 277 Participants | 276 Participants | 553 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 277 | 0 / 276 | 0 / 252 | 0 / 125 | 0 / 124 |
| other Total, other adverse events | 69 / 277 | 78 / 276 | 22 / 252 | 15 / 125 | 24 / 124 |
| serious Total, serious adverse events | 43 / 277 | 50 / 276 | 8 / 252 | 6 / 125 | 6 / 124 |
Outcome results
Primary
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
Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Core Treatment Period FKS518 | Percentage Change From Baseline in LS-BMD by DXA | Non-Inferiority Analysis | 5.52 Percentage change | Standard Error 0.292 |
| Core Treatment Period FKS518 | Percentage Change From Baseline in LS-BMD by DXA | Non-Superiority Analysis | 5.73 Percentage change | Standard Error 0.292 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in LS-BMD by DXA | Non-Inferiority Analysis | 5.07 Percentage change | Standard Error 0.297 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in LS-BMD by DXA | Non-Superiority Analysis | 5.03 Percentage change | Standard Error 0.297 |
90% CI: [-0.05, 0.96]
90% CI: [0.19, 1.2]
Secondary
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
Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Core Treatment Period FKS518 | Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | 1884 (ng*h/L) |
| Core Treatment Period US-Prolia | Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | 1862 (ng*h/L) |
Secondary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period FKS518 | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 1 Participants |
| Core Treatment Period US-Prolia | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 2 Participants |
| Core Treatment Period: FKS518; Transition Period: FKS518 | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 1 Participants |
| Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 0 Participants |
| Core Treatment Period: US-Prolia; Transition Period: US-Prolia | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 1 Participants |
| Overall Period: FKS518 | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 2 Participants |
| Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 1 Participants |
| Overall Period: US-Prolia | Number of Participants Who Experienced an Injection Site Reaction (ISR) | 2 Participants |
Secondary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 0 Participants |
| Core Treatment Period US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 7 Participants |
| Core Treatment Period: FKS518; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 0 Participants |
| Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 1 Participants |
| Core Treatment Period: US-Prolia; Transition Period: US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 0 Participants |
| Overall Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 0 Participants |
| Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 1 Participants |
| Overall Period: US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI) | 7 Participants |
Secondary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 185 Participants |
| Core Treatment Period US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 189 Participants |
| Core Treatment Period: FKS518; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 106 Participants |
| Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 58 Participants |
| Core Treatment Period: US-Prolia; Transition Period: US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 47 Participants |
| Overall Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 202 Participants |
| Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 102 Participants |
| Overall Period: US-Prolia | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 103 Participants |
Secondary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period FKS518 | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 43 Participants |
| Core Treatment Period US-Prolia | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 50 Participants |
| Core Treatment Period: FKS518; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 8 Participants |
| Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 6 Participants |
| Core Treatment Period: US-Prolia; Transition Period: US-Prolia | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 6 Participants |
| Overall Period: FKS518 | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 50 Participants |
| Overall Period: Core Treatment Period: US-Prolia; Transition Period: FKS518 | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 27 Participants |
| Overall Period: US-Prolia | Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE) | 33 Participants |
Secondary
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
Population: ITT Analysis Set: The ITT Analysis Set included all randomized participants. Participants were analyzed according to their randomized treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Core Treatment Period FKS518 | 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 |
| Core Treatment Period FKS518 | 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 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA | BMD at Femoral Neck at Week 52 | 1.85 Percentage change | Standard Error 0.291 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA | BMD at Total Hip at Week 52 | 2.88 Percentage change | Standard Error 0.223 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Core Treatment Period FKS518 | Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | -68.16 Percentage Change | Standard Error 4.241 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) | -64.47 Percentage Change | Standard Error 4.33 |
Secondary
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
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Core Treatment Period FKS518 | Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | -65.27 Percentage change | Standard Error 2.491 |
| Core Treatment Period US-Prolia | Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | -63.25 Percentage change | Standard Error 2.536 |