AVT03 With Prolia in Healthy Male Subjects

Healthy Male Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05126784
• Other study ID #: AVT03-GL-P01
• Status: Completed
• Phase: Phase 1
• Start date: June 29, 2022
• Est. completion date: October 16, 2023

Study information

• Verified date: May 2024
• Source: Alvotech Swiss AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: October 16, 2023
• Est. primary completion date: October 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 28 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Male Subjects

Intervention

Biological:
• AVT03
AVT03 (biosimilar to denosumab) will be given as single subcutaneous injection
• Prolia
Prolia (denosumab) will be given as single subcutaneous injection

Locations

Country	Name	City	State
Australia	Nucleus Network	Herston
New Zealand	NZCR Auckland	Auckland
New Zealand	NZCR Christchurch	Christchurch	Christchuch
South Africa	Farmovs	Bloemfontein

Sponsors (1)

Lead Sponsor	Collaborator
Alvotech Swiss AG

Countries where clinical trial is conducted

Australia,  New Zealand,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)]
Primary	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	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)
Secondary	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)]
Secondary	Safety incidence, nature and severity of adverse events		Screening to Day 252 (week 36)
Secondary	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)