AVT03 With Prolia in Healthy Male Subjects

Sponsor
Alvotech Swiss AG (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05126784
Collaborator
(none)
206
1
2
13.6
15.2

Study Details

Study Description

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, PD, safety and tolerability of AVT03 compared to Prolia when administered as a single 60 mg SC dose

Condition or Disease Intervention/Treatment Phase
  • Biological: Denosumab
N/A

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. 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 60mg AVT03 or 60mg Prolia as subcutaneous injection.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
206 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Arm 1: AVT03 Arm 2: ProliaArm 1: AVT03 Arm 2: Prolia
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind
Primary Purpose:
Basic Science
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
Actual Study Start Date :
Jun 29, 2022
Anticipated Primary Completion Date :
Aug 16, 2023
Anticipated Study Completion Date :
Aug 16, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: AVT03 Arm

AVT03 (denosumab) is the proposed biosimilar for Prolia (denosumab). Subjects in this arm will receive a single 60mg dose of AVT03 (denosumab) as a subcutaneous injection.

Biological: Denosumab
AVT03 (denosumab) or Prolia (denosumab) will be given as 1 time subcutaneous injection)
Other Names:
  • Prolia, AVT03, Biosimilar Denosumab
  • Active Comparator: Prolia Arm

    Prolia(denosumab) is the proposed comparator for AVT03 (denosumab). Subjects in this arm will receive a single 60mg dose of Prolia (denosumab) as a subcutaneous injection.

    Biological: Denosumab
    AVT03 (denosumab) or Prolia (denosumab) will be given as 1 time subcutaneous injection)
    Other Names:
  • Prolia, AVT03, Biosimilar Denosumab
  • Outcome Measures

    Primary Outcome Measures

    1. Area under the serum concentration-(AUC0-t) 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

    2. Maximum serum concentration Cmax [Day 1(week 1) to Day 252 (week 36)]

      Venous blood samples will be collected for measurement of maximum serum concentration of AVT03 and Prolia

    Secondary Outcome Measures

    1. PD_AUC0-last for CTX-1 (% inhibition)C terminal telopeptide of type 1 collagen) [Day 1(week 1) to Day 252 (week 36)]

      Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia

    2. Area under the concentration-time curve AUC0-24 [Day 1(week 1) to Day 162 (week 24)]]

      Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia

    3. Adverse Events [Screening to Day 252 (week 36)]

      Adverse events will be coded using MedDRA and grouped by system organ class and preferred term and summarised, by treatment group at the time of onset of the AE. The summary tables will present the number and percentage of total subjects and number of events, by system organ class and by preferred term. Injection related reactions will be listed and summarized by reaction using frequency counts and percentage, by treatment group.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    28 Years to 55 Years
    Sexes Eligible for Study:
    Male
    Accepts 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 [defined as glomerular filtration rate <45 mL/min], 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 (25[OH]D levels <15 ng/mL [37.5 nmol/L]) after supplementation at Screening

    • Known intolerance to calcium or vitamin D supplements

    • Any current active infections, including localized infections, or any recent history (within 1 week prior to IP administration) of active infections, cough or fever, or a history of recurrent or chronic infections

    • Known or suspected clinically relevant drug hypersensitivity to denosumab or any of its constituents, which in the opinion of the Investigator, contraindicates the subject's participation

    • History or presence of malignancy (except for successfully treated basal or squamous cell carcinoma)

    • Recent history of major surgery within 3 months prior to Day -1 and/or plan to have an operation (including invasive dental procedures) during the study period

    • Receipt of any investigational agent or drug within 8 weeks or 5 half-lives of that drug, whichever is longer, prior to IP administration in the current study

    • Previous treatment with denosumab (Prolia/Xgeva or its biosimilars)

    • Other criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 NZCR: New Zealand Clinical Research Christchurch Christchuch New Zealand 8011

    Sponsors and Collaborators

    • Alvotech Swiss AG

    Investigators

    • Study Director: Roshan Dias, Alvotech Swiss AG

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alvotech Swiss AG
    ClinicalTrials.gov Identifier:
    NCT05126784
    Other Study ID Numbers:
    • AVT03-GL-P01
    First Posted:
    Nov 19, 2021
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Alvotech Swiss AG
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 23, 2022