Healthy Male Subjects
Conditions
Keywords
Denosumab, Healthy Volunteers
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.
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.
Interventions
Sponsors
Alvotech Swiss AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Intervention model description
Arm 1: AVT03 Arm 2: US-Prolia
Eligibility
Sex/Gender
MALE
Age
28 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve (AUC0-last) from day 0 to day 252 | Day 1(week 1) to Day 252 (week 36) | Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) AVT03 and Prolia |
| Area under the serum concentration-time curve (AUC0-inf) from day 0 to day 252 | Time Frame: Day 1(week 1) to Day 252 (week 36)] | Venous blood samples will be collected for measurement of CTX-1 serum biomarker for AVT03 and Prolia. |
| Maximum serum concentration Cmax from day 0 to day 252 | Day 1(week 1) to Day 252 (week 36) | Venous blood samples will be collected for measurement of maximum serum concentration (Cmax) of AVT03 and Prolia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD_AUCE0 for CTX-1 (% inhibition) | Day 1(week 1) to Day 252 (week 36) | Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia |
| 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) | Venous blood samples will be collected for measurement of antidrug-antibodies against of AVT03 and Prolia |
| PK area under the concentration-time curve (AUC0-24) from Day 0 to Day 252 | Day 1(week 1) to Day 162 (week 24)] | Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia |
| Safety incidence, nature and severity of adverse events | Screening to Day 252 (week 36) | — |
Countries
Australia, New Zealand, South Africa
Outcome results
None listed