AVT03 With Prolia in Healthy Male Subjects

NCT05126784 | Completed Phase 1

• 1 other identifier: AVT03-GL-P01
• Study Type: interventional
• Target: 209
• Locations: 3 countries
• Sites: 4

Brief Summary

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

Conditions

Healthy Male Subjects

Keywords

Denosumab; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Area under the serum concentration-time curve (AUC0-last) from day 0 to day 252

  Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) AVT03 and Prolia

  Day 1(week 1) to Day 252 (week 36)

• Area under the serum concentration-time curve (AUC0-inf) from day 0 to day 252

  Venous blood samples will be collected for measurement of CTX-1 serum biomarker for AVT03 and Prolia.

  Time Frame: Day 1(week 1) to Day 252 (week 36)]

• Maximum serum concentration Cmax from day 0 to day 252

  Venous blood samples will be collected for measurement of maximum serum concentration (Cmax) of AVT03 and Prolia.

  Day 1(week 1) to Day 252 (week 36)

Secondary Outcomes (4)

• PD_AUCE0 for CTX-1 (% inhibition)

  Day 1(week 1) to Day 252 (week 36)

• PK area under the concentration-time curve (AUC0-24) from Day 0 to Day 252

  Day 1(week 1) to Day 162 (week 24)]

• Safety incidence, nature and severity of adverse events

  Screening to Day 252 (week 36)

• Immunogenicity presence and titers of ADAs and presence of nAbs against AVT03 and Prolia

  Time Frame: Day 1(week 1) to Day 252 (week 36)

Study Arms (2)

AVT03 Arm

EXPERIMENTAL

AVT03 (denosumab) is the proposed biosimilar for Prolia (denosumab). Subjects in this arm will receive a single 60mg dose of AVT03 (denosumab) as a subcutaneous injection.

Biological: AVT03

Prolia Arm

ACTIVE COMPARATOR

Prolia(denosumab) is the proposed comparator for AVT03 (denosumab). Subjects in this arm will receive a single 60mg dose of Prolia (denosumab) as a subcutaneous injection.

Biological: Prolia

Interventions

AVT03 BIOLOGICAL

AVT03 (biosimilar to denosumab) will be given as single subcutaneous injection

Also known as: AVT03, Biosimilar Denosumab

AVT03 Arm

Prolia BIOLOGICAL

Prolia (denosumab) will be given as single subcutaneous injection

Also known as: Denosumab

Prolia Arm

Eligibility Criteria

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

You may qualify if:

• Male subjects who are 28 to 55 years old, inclusive
• Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index (BMI) of 17.0 to 32.0 kg/m2 (inclusive)at Screening and Day -1
• Medical history without evidence of a clinically significant disorder, condition, or disease that, in the opinion of the Investigator, would pose a risk to subject safety

You may not qualify if:

• Any 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, hyperthyroidism, hypothyroidism, 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, recent bone fracture \[within 6 months\], and malabsorption syndrome)
• Have osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery) within 6 months prior to Day 1 or intend to undergo such procedures during the study period, poor oral hygiene, periodontal, and/or pre existing dental disease
• Have bone fractures within 6 months prior to Day -1.
• Have a history of immunodeficiency
• Those with skin allergies, or are susceptible to autoinflammatory skin disorders, or prone to the development of allergic skin inflammation
• Abnormal serum calcium: current hypocalcemia or hypercalcemia at Screening. Serum calcium levels must be within reference ranges.
• Known vitamin D deficiency

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (4)

Nucleus Network

Herston, Australia

Location

NZCR Christchurch

Christchurch, Christchuch, New Zealand

Location

NZCR Auckland

Auckland, New Zealand

Location

Farmovs

Bloemfontein, South Africa

Location

Related Publications (1)

• Pretorius A, Bullo F, Jaskiewicz L, Stamatakos S, Otto H, Rai M, Ruffieux R, Sattar A, Leutz S, Berti F. A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults. Expert Opin Investig Drugs. 2025 Jun;34(6):527-537. doi: 10.1080/13543784.2025.2505466. Epub 2025 May 16.

  PMID: 40357744 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

Study Officials

• Felicitas Bullo

  Alvotech

  STUDY DIRECTOR

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

Model Details: Arm 1: AVT03 Arm 2: US-Prolia

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 19, 2021
• Study Start: June 29, 2022
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

AU (1); ZA (1); NZ (2)