Clinical trial NCT05876949: AVT03 With Xgeva in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: This is a Phase I Study Conducted in Healthy Volunteers
Keywords: Denosumab
Healthy Volunteers
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 208
Sex: MALE
Minimum age (years): 28
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Co-primary PK Endpoint Cmax: Maximum Serum Concentration
timeFrame: Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study
measure: 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
timeFrame: Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study
Secondary outcomes:
measure: PK_ AUC0-inf: Comprised of AUC0-t and AUC Extrapolated From Time t to Time Infinity.
timeFrame: Day 1 (pre-dose, 8h and 12h post-dose), Day 2 to Day 13 (daily), Day 15, Day 18, Day 22, Day 25, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 112, Day 126, Day 141, Day 162 and Day 196 (week 28) / End of study
measure: Safety Incidence, Nature and Severity of Adverse Events.
timeFrame: Day 1(week 1) to Day 196 (week 28)]
measure: Immunogenicity Presence of ADAs and Presence of nAbs Against AVT03 and Xgeva
timeFrame: Day 1, Day 8, Day 15, Day 29, Day 57, Day 71, Day 112, Day 141, Day 196/EoS
Other outcomes:
Locations:
city: Józefów
country: Poland
facility: Biokinetica
city: Bloemfontein
country: South Africa
facility: Farmovs
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
affiliation: Alvotech Swiss AG
name: Felicitas Bullo
role: STUDY_DIRECTOR
References: