Randomized, Double-Blind, Parallel Design, 2-arm,Multicenter Study Assessing the Biosimilarity of AVT03 and US-Prolia® in Postmenopausal Women With Osteoporosis

• Status: Not yet recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: Female

Summary

This is a randomized, double-blind, parallel design, repeat dose, 2 arm, multicenter study comparing the efficacy, safety, immunogenicity, and PK profiles of AVT03 and Prolia in postmenopausal women with osteoporosis.

After the screening activities, eligible subjects will be randomized in a 1:1 ratio to receive either AVT03 60 mg or Prolia® 60 mg, administered as a subcutaneous (s.c.) injection on Day 1 and Day 180 (Month 6). At Month 12, subjects in AVT03 treatment group will receive a third dose of AVT03 60 mg administered s.c. while subjects in Prolia® treatment group will be re-randomized in a 1:1 ratio to receive either Prolia 60 mg or AVT03 60 mg on Day 365 (Month 12), administered as a subcutaneous injection.

Afterwards, the subjects will be followed until the End of Study (EoS) Visit at Month 18 (ie, 6 months after the last dose at Month 12).

Approximately 30 clinical sites will participate in this study. The planned number of randomized patients is approximately 476.

Expected countries : Bulgaria, Czech Republic, Georgia, Poland, South Africa.

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

Details

• Lead Sponsor: Alvotech Swiss AG
• Treatments: Denosumab

Criteria

Inclusion Criteria

1. Postmenopausal women with osteoporosis willing to sign an informed consent form(ICF)and able to undergo protocol related procedures.

2. Age: ≥50 years.

3. Female subject is postmenopausal according to 1 of the following criteria:

1. Spontaneous amenorrhea for ≥12 consecutive months

2. Biochemical criteria of menopause, follicle-stimulating hormone, >40 IU/L except surgically sterile

3. Having had bilateral oophorectomy ≥6 weeks prior to Screening

4. Body Mass Index (BMI): 18.5.0-32.0 kg/m2

5. A baseline dual-energy x-ray absorptiometry scan with a T score less than or equal to -2.5 and greater than or equal to -4.0 at the LS (L1 to L4), total hip,and/or femoral neck.

6. At least 2 consecutive evaluable lumbar vertebrae and at least 1 evaluable hip

7. Willing to receive calcium plus vitamin D supplements.

8. No history or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the Investigator, would pose a risk to subject safety.

9. Resting supine systolic blood pressure of ≤150mmHg and diastolic blood pressure of ≤90mmHg.

10.12-leadECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Investigator.

11. Subject smokes <10 cigarettes per day within 3 months of Screening. Note: It is strongly recommended that subjects do not smoke during their participation in the study.

12. Recommended to abstain from alcohol from 48 hours prior to study drug administration, and 24 hours prior to study visits.

Exclusion Criteria

1. Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism

2. History and/or presence of 1 severe or more than 1 moderate vertebral fractures confirmed by x-ray.

3. History of hip fracture

4. Presence of active healing fractures

5. Previous treatment with denosumab and previous use of the following medications:

1. Intravenous bisphosphonates, fluoride or strontium ranelate within 5 years prior to Screening

2. Oral bisphosphonatesused >3 years cumulative use, and any dose within 12 months of Screening

3. Parathyroid hormone (PTH) or PTH derivatives, eg, teriparatide and selective estrogen receptor modulators (SERMs), eg, raloxifene within 1 year of Screening

4. Calcitonin within 6 months of Screening

5. Other bone metabolism drugs administration within the last 3 months

6. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures

7. Evidence of hypo/hypercalcemia at Screening.

8. Known vitamin D deficiency

9. Known intolerance to calcium or vitamin D supplement.

10. Any current active infections, including localized infections, or any recent history of active infections or a history of recurrent or chronic infections.

11. Presence of known current infection with hepatitis B or presence of positive serology-ie, hepatitis B surface antigen (HBsAg)and or core antigen (HBcAg),hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) at Screening.

12. Haematology and chemistry laboratory results outside the reference ranges, which are clinically significant, and, in the opinion of the Investigator or designee, could cause this study to be detrimental to the subject.

13. Donation of more than 500mL of blood within the 8 weeks prior to study drug administration.

14. Hypersensitivity to denosumab or its constituents.

15. A recent history of major surgery including spine surgery within 3 months prior to randomization.

16. History or presence of malignancy within5 years(with the exception of successfully treated basal cell carcinoma).

17. Inability to communicate or cooperate with the Investigator because of language difficulties or poor mental development or incapacitation.

18. A history (within the previous 3 years) or evidence of alcohol or drug abuse (including soft drugs like cannabis products).

19. Vaccination with a live vaccine with the exception of flu vaccine within the previous month. Coronavirus disease 2019 vaccination is not considered an exclusion criterion.

20. Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk.

21. Current participation or history of participation in an investigational trial in the last 30 days or 5 half-lives - whichever is longer.