Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND

A Randomized, Double-Blind, Parallel Design, Repeat Dose, 2-arm, Multicenter Study Comparing the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profiles of AVT03 and US-Prolia® in Postmenopausal Women With Osteoporosis, ALVOBOND

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

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

Afterwards, the subjects will be followed until the End of Study (EoS) Visit.

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

2. A baseline dual-energy x-ray absorptiometry (DXA) scan with a T score ≤-2.5 and

   • 4.0 at the LS (L1 to L4)and/or, total hip, and/or femoral neck.

3. Age: ≥50 years.

4. 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

5. Willing to receive calcium plus vitamin D supplements.

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

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. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures
6. Evidence of hypo/hypercalcemia at Screening
7. Known vitamin D deficiency
8. Known intolerance to calcium and vitamin D supplement.