Clinical trial NCT05126784: AVT03 With Prolia in Healthy Male Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male Subjects
Keywords: Denosumab
Healthy Volunteers
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 209
Sex: MALE
Minimum age (years): 28
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: AVT03 Arm 2: US-Prolia
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under the serum concentration-time curve (AUC0-last) from day 0 to day 252
timeFrame: Day 1(week 1) to Day 252 (week 36)
measure: Area under the serum concentration-time curve (AUC0-inf) from day 0 to day 252
timeFrame: Time Frame: Day 1(week 1) to Day 252 (week 36)]
measure: Maximum serum concentration Cmax from day 0 to day 252
timeFrame: Day 1(week 1) to Day 252 (week 36)
Secondary outcomes:
measure: PD_AUCE0 for CTX-1 (% inhibition)
timeFrame: Day 1(week 1) to Day 252 (week 36)
measure: PK area under the concentration-time curve (AUC0-24) from Day 0 to Day 252
timeFrame: Day 1(week 1) to Day 162 (week 24)]
measure: Safety incidence, nature and severity of adverse events
timeFrame: Screening to Day 252 (week 36)
measure: Immunogenicity presence and titers of ADAs and presence of nAbs against AVT03 and Prolia
timeFrame: Time Frame: Day 1(week 1) to Day 252 (week 36)
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Nucleus Network
city: Christchurch
country: New Zealand
facility: NZCR Christchurch
state: Christchuch
city: Auckland
country: New Zealand
facility: NZCR Auckland
city: Bloemfontein
country: South Africa
facility: Farmovs
Study officials:
affiliation: Alvotech
name: Felicitas Bullo
role: STUDY_DIRECTOR
References: