AVT03 With Prolia in Healthy Male Subjects

A Randomized, Double-blind, Single-dose, Parallel-group Design, 2 Arm Study Comparing the Pharmacokinetic, Pharmacodynamic, Safety, Tolerability, and Immunogenicity Profiles of AVT03 and Prolia® in Healthy Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects
• Intervention / Treatment: Biological: AVT03; Biological: Prolia

Detailed Description

The study will consist of a 4 week screening period, a 252 day (36 weeks) treatment and assessment period, and an End of Study (EOS) visit on week 36 on Day 252. Subjects will undertake a screening visit between Day -28 and Day -1 to determine their eligibility for the study. On Day 1, eligible subjects will be randomized and will receive a single dose of AVT03 or Prolia as subcutaneous injection.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia
    • Nucleus Network
• New Zealand
  • Auckland, New Zealand
    • NZCR Auckland
  • Christchuch
    • Christchurch, Christchuch, New Zealand
      • Nzcr Christchurch
• South Africa
  • Bloemfontein, South Africa
    • FARMOVS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVT03 Arm; 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; AVT03 (biosimilar to denosumab) will be given as single subcutaneous injection; Other Names: AVT03, Biosimilar Denosumab
Active Comparator: Prolia Arm; 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; Prolia (denosumab) will be given as single subcutaneous injection; Other Names: Denosumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD_AUCE0 for CTX-1 (% inhibition)	Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia	Day 1(week 1) to Day 252 (week 36)
PK area under the concentration-time curve (AUC0-24) from Day 0 to Day 252	Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia	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	Venous blood samples will be collected for measurement of antidrug-antibodies against of AVT03 and Prolia	Time Frame: Day 1(week 1) to Day 252 (week 36)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Actual): October 16, 2023
• Study Completion (Actual): October 16, 2023

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Denosumab
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: AVT03-GL-P01

Drug and device information, study documents

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