Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND (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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Biological: AVT03; Biological: Denosumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Investigational Site 3501
  • Plovdiv, Bulgaria
    • Investigational Site 3503
  • Stara Zagora, Bulgaria
    • Investigational Site 3502
• Czechia
  • Praha, Czechia
    • Investigational Site 4201
  • Uherské Hradiště, Czechia
    • Investigational Site 4202
• Georgia
  • Tbilisi, Georgia
    • Investigational Site 9901
  • Tbilisi, Georgia
    • Investigational Site 9902
  • Tbilisi, Georgia
    • Investigational Site 9903
  • Tbilisi, Georgia
    • Investigational Site 9904
  • Tbilisi, Georgia
    • Investigational Site 9905
  • Tbilisi, Georgia
    • Investigational Site 9906
• Poland
  • Białystok, Poland
    • Investigational Site 4803
  • Białystok, Poland
    • Investigational Site 4804
  • Kraków, Poland
    • Investigational Site 4802
  • Kraków, Poland
    • Investigational Site 4807
  • Lublin, Poland
    • Investigational Site 4811
  • Poznań, Poland
    • Investigational Site 4812
  • Skierniewice, Poland
    • Investigational Site 4801
  • Warsaw, Poland
    • Investigational Site 4809
  • Zamość, Poland
    • Investigational Site 4810
  • Łódź, Poland
    • Investigational Site 4806
  • Świdnik, Poland
    • Investigational Site 4805
• South Africa
  • Bloemfontein, South Africa
    • Investigational Site 2705
  • Cape Town, South Africa
    • Investigational Site 2714
  • Centurion, South Africa
    • Investigational Site 2707
  • Centurion, South Africa
    • Investigational Site 2708
  • Groenkloof, South Africa
    • Investigational Site 2710
  • Johannesburg, South Africa
    • Investigational Site 2712
  • Kwadukuza, South Africa
    • Investigational Site 2702
  • Parow, South Africa
    • Investigational Site 2711
  • Port Elizabeth, South Africa
    • Investigational Site 2701
  • Pretoria, South Africa
    • Investigational Site 2706
  • Pretoria, South Africa
    • Investigational Site 2713
  • Worcester, South Africa
    • Investigational Site 2703

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in LS BMD at Month 12 to Demonstrate Comparable Efficacy of AVT03 and Prolia®.	Percent Change From Baseline in LS BMD at Month 12 to demonstrate comparable efficacy of AVT03 and Prolia®.	Baseline to Month 12
To Demonstrate Comparable Profile of AVT03 and Prolia in Terms of Area Under the Percent Change From Baseline in Serum C-telopeptide of Type 1 Collagen (AUEC of %Cfb sCTX-1)		Baseline to Month 6

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 6, Month18
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 months	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
Percent Change From Baseline in sCTX-1	Percent change from Baseline in sCTX-1 at 3, 6, 9, 12 and 18 months	Month 3, Month 6, Month 9, Month 12 and Month 18
Incidence, Nature and Severity of Adverse Events Including Adverse Drug Reactions		Month 18
Frequency and Severity of Injection Site Reactions		Month 12
Frequency and Severity of Findings in Routine Safety Parameters		Month 18
Frequency and Titer of Anti-drug Antibodies and Frequency of Neutralizing Antibodies Against AVT03 and Prolia		Month 18
Serum Trough Concentration of AVT03 and Prolia		Month 18

Collaborators and Investigators

• Sponsor: Alvotech Swiss AG
• Investigators: Study Director: Felicitas Bullo, Alvotech Swiss AG

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): October 28, 2024

Study Registration Dates

• First Submitted: May 24, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Postmenopausal Osteoporosis, Denosumab, Alvotech
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: AVT03-GL-C01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes