Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND

NCT05395091 | Completed Phase 3 Results FDA Drug

• 1 other identifier: AVT03-GL-C01
• Study Type: interventional
• Target: 532
• Locations: 5 countries
• Sites: 34

Brief Summary

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.

Conditions

Osteoporosis, Postmenopausal

Keywords

Postmenopausal Osteoporosis, Denosumab, Alvotech

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Percent Change From Baseline in LS BMD

  Month 6, Month18

• Percent Change From Baseline in Hip and Femoral Neck BMD

  Month 6, Month 12, Month 18

• Incidence of New Morphometric Vertebral Fractures

  Month 12 and 18

• Percent Change From Baseline in sCTX-1

  Month 3, Month 6, Month 9, Month 12 and Month 18

• Incidence, Nature and Severity of Adverse Events Including Adverse Drug Reactions

  Month 18

Study Arms (2)

AVT03

EXPERIMENTAL

AVT03 is the proposed biosimilar for Prolia.

Biological: AVT03

Prolia

ACTIVE COMPARATOR

Biological: Denosumab

Interventions

AVT03 BIOLOGICAL

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.

AVT03

Denosumab BIOLOGICAL

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.

Also known as: Prolia

Prolia

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• Evidence of hypo/hypercalcemia at Screening
• Known vitamin D deficiency
• Known intolerance to calcium and vitamin D supplement.

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (34)

Investigational Site 3501

Plovdiv, Bulgaria

Location

Investigational Site 3503

Plovdiv, Bulgaria

Location

Investigational Site 3502

Stara Zagora, Bulgaria

Location

Investigational Site 4201

Prague, Czechia

Location

Investigational Site 4202

Uherské Hradiště, Czechia

Location

Investigational Site 9901

Tbilisi, Georgia

Location

Investigational Site 9902

Tbilisi, Georgia

Location

Investigational Site 9903

Tbilisi, Georgia

Location

Investigational Site 9904

Tbilisi, Georgia

Location

Investigational Site 9905

Tbilisi, Georgia

Location

Investigational Site 9906

Tbilisi, Georgia

Location

Investigational Site 4803

Bialystok, Poland

Location

Investigational Site 4804

Bialystok, Poland

Location

Investigational Site 4802

Krakow, Poland

Location

Investigational Site 4807

Krakow, Poland

Location

Investigational Site 4806

Lodz, Poland

Location

Investigational Site 4811

Lublin, Poland

Location

Investigational Site 4812

Poznan, Poland

Location

Investigational Site 4801

Skierniewice, Poland

Location

Investigational Site 4805

Świdnik, Poland

Location

Investigational Site 4809

Warsaw, Poland

Location

Investigational Site 4810

Zamość, Poland

Location

Investigational Site 2705

Bloemfontein, South Africa

Location

Investigational Site 2714

Cape Town, South Africa

Location

Investigational Site 2707

Centurion, South Africa

Location

Investigational Site 2708

Centurion, South Africa

Location

Investigational Site 2710

Groenkloof, South Africa

Location

Investigational Site 2712

Johannesburg, South Africa

Location

Investigational Site 2702

KwaDukuza, South Africa

Location

Investigational Site 2711

Parow, South Africa

Location

Investigational Site 2701

Port Elizabeth, South Africa

Location

Investigational Site 2706

Pretoria, South Africa

Location

Investigational Site 2713

Pretoria, South Africa

Location

Investigational Site 2703

Worcester, South Africa

Location

Related Publications (1)

• Lortkipanidze M, de Villiers T, Kania G, Bullo F, Jaskiewicz L, Stamatakos S, Rai M, Haliduola H, Otto H, Sattar A, Leutz S, Berti F. A randomized, double blind, parallel design, repeat dose, 2-arm, multicenter study comparing the efficacy, safety, immunogenicity, and pharmacokinetic profiles of a denosumab biosimilar, AVT03, in postmenopausal women with osteoporosis. Expert Opin Biol Ther. 2025 Aug;25(8):899-912. doi: 10.1080/14712598.2025.2538609. Epub 2025 Jul 28.

  PMID: 40698538 DERIVED

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Development and Medical Lead
• Organization: Alvotech Swiss AG

alvotech.clinical@alvotech.com

+41 78 659 89 89

Study Officials

• Felicitas Bullo

  Alvotech Swiss AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 27, 2022
• Study Start: August 23, 2022
• Primary Completion: May 7, 2024
• Study Completion: October 28, 2024
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Locations

BU (3); ZA (12); CZ (2); PL (11); GE (6)