Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND

Study Overview
=================
Brief 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 were 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). 32 clinical sites are now participating in this study and total of 532 patients have been randomized. Ccountries : Bulgaria, Czech Republic, Georgia, Poland, South Africa.

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

Conditions
-----------------
Osteoporosis, Postmenopausal

Intervention / Treatment
-----------------
* Biological: denosumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Postmenopausal women with osteoporosis willing to sign an informed consent form (ICF)and able to undergo protocol related procedures. A baseline dual-energy x-ray absorptiometry (DXA) scan with a T score ≤-2.5 and 4.0 at the LS (L1 to L4), total hip, and/or femoral neck. Age: ≥50 years. Female subject is postmenopausal according to 1 of the following criteria: Spontaneous amenorrhea for ≥12 consecutive months Biochemical criteria of menopause, follicle-stimulating hormone, >40 IU/L except surgically sterile Having had bilateral oophorectomy ≥6 weeks prior to Screening Willing to receive calcium plus vitamin D supplements. 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 Exclusion Criteria Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism History and/or presence of 1 severe or more than 1 moderate vertebral fractures confirmed by x-ray. History of hip fracture Presence of active healing fractures Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures Any current active infections, including localized infections, or any recent history of active infections or a history of recurrent or

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVT03<br>AVT03 is the proposed biosimilar for Prolia. Subjects in this arm will receive AVT03 60mg administered s.c. on Day 1 and Day 180/Month 6. At Month 12, subjects in the AVT03 arm will receive a third dose of AVT03 60 mg | Biological: denosumab<br>* AVT03 (denosumab) is a recombinant fully human IgG2 monoclonal antibody to RANKL developed as a subcutaneous injection.<br>* Other names: Prolia;|
| Active Comparator: Prolia<br>Subjects will receive 60mg of commercially available Prolia, administered s.c. on Day 1 and Day 180/Month 6. At Month 12, subjects in the Prolia treatment group will be re-randomized in a 1:1 ratio to receive either: Group 2a:Subjects will receive AVT03 60 mg administered s.c. on Day365. Group 2b:Subjects will receive Prolia 60 mg administered s.c. on Day365. | Biological: denosumab<br>* AVT03 (denosumab) is a recombinant fully human IgG2 monoclonal antibody to RANKL developed as a subcutaneous injection.<br>* Other names: Prolia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate clinical similarity of AVT03 and Prolia® in terms percent change from Baseline in Bone Mineral Density (BMD) at 12 months. | Percent change from Baseline in lumbar spine (LS) BMD at 12 months | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in LS BMD | Percent change from Baseline in LS BMD at 6 and 18 months | Month 18 | 
| Percent change from Baseline in hip and femoral neck BMD | Percent change from Baseline in hip and femoral neck BMD at Month 6, 12 and 18 | Month 6, Month 12, Month 18 | 
| Incidence of new morphometric vertebral fractures | Incidence of new morphometric vertebral fractures at 12 and 18 months | Month 12 and 18 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postmenopausal Osteoporosis, Denosumab, Alvotech