AVT03 With Xgeva in Healthy Male Subjects

A Randomized, Double-blind, Parallel Design, Single Dose, 2-arm Study Comparing the Pharmacokinetic, Safety and Immunogenicity Profiles of AVT03 and US-Xgeva® in Healthy Male Subjects

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

Study Overview

• Status: Active, not recruiting
• Conditions: This is a Phase Study Conducted in Healthy Volunteers
• Intervention / Treatment: Biological: AVT03; Biological: Denosumab

Detailed Description

The study will consist of screening period, a 196 day (28 weeks) treatment and assessment period, and an End of Study (EOS) visit on week 32 on Day 196. Subjects will undertake a screening visit between Day -28 and Day -1 to determine their eligibility for the study. Subjects who meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1), during which their continued eligibility will be assessed up to Day 1 prior to dosing. On Day 1, eligible subjects will be randomized and will receive a single dose of 120mg AVT03 or 120mg Xgeva as subcutaneous injection.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Bloemfontein, South Africa
    • Investigational Site 2701

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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.
2. Male subjects who are 28 to 55 years old, inclusive, at the time of signing the ICF.
3. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Have bone fractures, presence of active healing fractures, or recent bone fracture
4. Abnormal serum calcium.
5. 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: Experimental Arm AVT03 120mg; 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; AVT03 will be given as 1 time subcutaneous injection; Other Names: AVT03 proposed Biosimilar to Denosumab
Active Comparator: Active Comparator Xgeva 120mg; 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; Xgeva (denosumab) will be given as 1 time subcutaneous injection; Other Names: Xgeva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-primary PK endpoint_Cmax: maximum serum concentration	Samples will be collected for measurement	Day 1(week 1) to Day 196 (week 28)
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(week 1) to Day 196 (week 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK_ AUC0-inf: comprised of AUC0-t and AUC extrapolated from time t to time infinity.	Samples will be collected for measurement	Day 1(week 1) to Day 196 (week 28)]
Safety Incidence, nature and severity of adverse events.		Day 1(week 1) to Day 196 (week 28)]
Immunogenicity_Presence and titer of ADAs and presence of nAbs against AVT03 and Xgeva	Samples will be collected for measurement	Day 1(week 1) to Day 196 (week 28)

Collaborators and Investigators

• Sponsor: Alvotech Swiss AG
• Investigators: Study Director: Lukasz Jaskiewicz, Alvotech

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Estimated): April 13, 2024
• Study Completion (Estimated): April 13, 2024

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Denosumab
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: AVT03-GL-P03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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