AVT03 With Xgeva in Healthy Male Subjects

NCT05876949 | Completed Phase 1 Results

• 1 other identifier: AVT03-GL-P03
• Study Type: interventional
• Target: 208
• Locations: 3 countries
• Sites: 3

Brief Summary

This study has been designed as a randomized, double-blind, parallel-group study and in healthy adult male subjects of age 28 years to 55 years old. The study will assess the PK, safety and tolerability of AVT03 compared to US-Xgeva when administered as a single 120 mg SC dose

Conditions

This is a Phase I Study Conducted in Healthy Volunteers

Keywords

Denosumab; Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Co-primary PK Endpoint Cmax: Maximum Serum Concentration

  Samples will be collected for measurement

  Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study

• Co-primary PK endpoint_AUC0-t: Area Under the Serum Concentration-time Curve up to Time t, Where t is the Last Time Point With a Concentration Above the Lower Limit of Quantitation

  Samples will be collected for measurement

  Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study

Secondary Outcomes (3)

• PK_ AUC0-inf: Comprised of AUC0-t and AUC Extrapolated From Time t to Time Infinity.

  Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study

• Safety Incidence, Nature and Severity of Adverse Events.

  Day 1(week 1) to Day 196 (week 28)]

• Immunogenicity Presence of ADAs and Presence of nAbs Against AVT03 and Xgeva

  Day 1, Day 8, Day 15, Day 29, Day 57, Day 71, Day 112, Day 141, Day 196/EoS

Study Arms (2)

Experimental Arm AVT03 120mg

EXPERIMENTAL

AVT03 is the proposed biosimilar for Xgeva (denosumab). Subjects in this arm will receive a single 120mg dose of AVT03 as a subcutaneous injection

Biological: AVT03

Active Comparator Xgeva 120mg

ACTIVE COMPARATOR

Xgeva (denosumab) is the proposed active comparator for AVT03. Subjects in this arm will receive a single 120mg dose of Xgeva (denosumab) as a subcutaneous injection

Biological: Denosumab

Interventions

AVT03 BIOLOGICAL

AVT03 will be given as 1 time subcutaneous injection

Also known as: AVT03 proposed Biosimilar to Denosumab

Experimental Arm AVT03 120mg

Denosumab BIOLOGICAL

Xgeva (denosumab) will be given as 1 time subcutaneous injection

Also known as: Xgeva

Active Comparator Xgeva 120mg

Eligibility Criteria

• Age: 28 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Male subjects who are 28 to 55 years old, inclusive, at the time of signing the ICF.
• Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index of 17.0 to 32 kg/m2 at Screening and Day -1.

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 such as, but not limited to: osteoporosis, osteogenesis imperfecta, hyperparathyroidism,, non-controlled hyperthyroidism osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease, Paget's disease of the bone, malabsorption syndrome.
• Have osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery) or intend to undergo such procedures during the study period, poor oral hygiene, periodontal, and/or pre-existing dental disease.
• Have bone fractures, presence of active healing fractures, or recent bone fracture
• Abnormal serum calcium.
• Known vitamin D deficiency.

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (3)

Biokinetica

Józefów, Poland

Location

Farmovs

Bloemfontein, South Africa

Location

Richmond Pharmacology

London, United Kingdom

Location

Related Publications (1)

• Tomaszewska-Kiecana M, Bullo F, Jaskiewicz L, Stamatakos S, Otto H, Rai M, Sattar A, Leutz S, Berti F. A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults. Expert Opin Investig Drugs. 2025 Jun;34(6):539-546. doi: 10.1080/13543784.2025.2505469. Epub 2025 May 16.

  PMID: 40357869 DERIVED

MeSH Terms

Interventions

Denosumab

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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 26, 2023
• Study Start: July 21, 2023
• Primary Completion: April 15, 2024
• Study Completion: April 15, 2024
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); PL (1); ZA (1)