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

• Status: Recruiting
• Trial end date: 2023-03-20
• Target enrollment: 0
• Participant gender: Female

Summary

The primary objective of this study is to demonstrate equivalent efficacy of FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO).

Participants will be randomized at the beginning of the Double-blind Core Treatment Period (Baseline to Week 52) to receive either FKS518 or US-licensed Prolia on Day 1, and then every 26 weeks for up to 52 weeks.

At the beginning of the Double-blind Transition Period (Week 52 to Week 78), participants who received US-licensed Prolia will be re-randomized to either continue receiving US-licensed Prolia every 26 weeks for up to 78 weeks, or switch to receive FKS518 every 26 weeks for up to 78 weeks.

Participants who were randomized to receive FKS518 at the beginning of the Double-blind Core Treatment Period will continue to receive this treatment during the Double-blind Transition Period.

For Marketing Authorization Application (MAA) in the EU and European Economic Area (EEA) only: The primary objective is to demonstrate equivalent efficacy and pharmacodynamics of the proposed biosimilar denosumab FKS518 to US-Prolia in women with PMO.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fresenius Kabi SwissBioSim GmbH
• Treatments: Denosumab

Criteria

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.