AVT03 With Prolia in Healthy Male Subjects

Sponsor
Alvotech Swiss AG (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05126784
Collaborator
(none)
206
Enrollment
2
Arms
13
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study has been designed as a multicentre, randomised, double-blind study of AVT03 in healthy adult Male subjects. 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 DiseaseIntervention/TreatmentPhase
  • Biological: Denosumab
Phase 1

Detailed Description

This study is a (First In Human)FIH, multicenter, randomized, double-blinded, 2-arm, parallel-group study of AVT03 compared with Prolia when administered as a single 60 mg SC injection in healthy adult male subjects.

The study will consist of a 4 week Screening period, a 28-week treatment and assessment period, and an End of Study (EOS) visit on Day 196. Subjects will undertake a Screening visit between Day -28 and Day -1 to determine their eligibility in 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 AVT03 or Prolia. Subjects will receive adequate calcium and vitamin D supplements during the study as required (based on the Investigator's discretion), starting from Screening to ensure subjects have appropriate levels of these parameters at the time of IP administration.

A staggered sentinel dosing strategy will be implemented as a safety measure, with equal numbers of subjects randomized to each treatment in a 1:1 ratio: Sentinel Group 1 (n = 2 subjects [1 per group]), Sentinel Group 2 (n = 4 subjects [2 per group]), and Sentinel Group 3 (n = 6 subjects [3 per group]). Following investigational product (IP) administration, there will be at least 72 hours of close observation and safety monitoring by the Investigator for each subject and between sentinel groups (ie, at least 72 hours should have elapsed following IP administration for the last subject in each sentinel group). Provided no significant safety or tolerability concerns (or events that meet the study stopping criteria) have been identified in the previous sentinel group following a safety review and discussion between the Investigator, Medical Monitor, and Sponsor Medical Lead, the next sentinel group of subjects will be randomized and dosed. Once the IP dose is deemed to be safe and well tolerated in all 3 sentinel groups, the remaining subjects (n = 194 [94 per group]) will be randomized and dosed.

Sentinel subjects will remain confined to the study site from Day -1 to Day 4 (72 hours postdose); all remaining subjects will be confined to the study site from Day -1 up to Day 3 (48 hours postdose). Following dosing, PK, PD, safety, tolerability, and other assessments will be performed according to the Schedule of Assessments (Table 1). Subjects will return to the study site on an outpatient basis daily up to Day 12, then once a week from Day 15 to Day 29, followed by once approximately every 2 weeks up to Day 141, and finally on Day 196 for the EOS visit.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
206 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomization to AVT03 or Prolia will be performed in a 1:1 ratio on Day 1. The randomization will be stratified by ethnicity and body weight at Day 1 as follows: Japanese, non-Japanese ≤80 kg, and non-Japanese >80 kg. A copy of the randomization schedule will be provided to the unblinded study site pharmacist.Randomization to AVT03 or Prolia will be performed in a 1:1 ratio on Day 1. The randomization will be stratified by ethnicity and body weight at Day 1 as follows: Japanese, non-Japanese ≤80 kg, and non-Japanese >80 kg. A copy of the randomization schedule will be provided to the unblinded study site pharmacist.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind
Primary Purpose:
Basic Science
Official Title:
A First-in-human, 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
Anticipated Study Start Date :
May 30, 2022
Anticipated Primary Completion Date :
Jun 30, 2023
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: AVT03 Arm

AVT03 is the proposed biosimilar for Prolia. Subjects in this arm will receive a single 60mg dose of Alvotech's AVT03

Biological: Denosumab
Both the AVT03, and Prolia will be supplied as 60mg Pre-Filled Syringes and used to treat osteoporosis
Other Names:
  • AVT03, Prolia
  • Active Comparator: Prolia Arm

    Subjects in this arm will get 60mg of Commercially available Prolia

    Biological: Denosumab
    Both the AVT03, and Prolia will be supplied as 60mg Pre-Filled Syringes and used to treat osteoporosis
    Other Names:
  • AVT03, Prolia
  • Outcome Measures

    Primary Outcome Measures

    1. PK_Area under the serum concentration-time curve AUC0-t [Day 1 to Day 196]

      Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) of AVT03 and Prolia

    2. PK_Maximum serum concentration Cmax [Day 1 to Day 196]

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

    Secondary Outcome Measures

    1. PD Parameters_AUEC0 Wk16 for CTX-1 (% inhibition), [Day 1 to Day 196]

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

    2. PD Parameters_ AUEC0-Wk16 for P1NP [Day 1 to Day 196]

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

    3. PD Parameters _Percent change in levels of BSAP [Day 1 to Day 196]

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

    4. PD Parameters _Percent change in levels of OC [Day 1 to Day 196]

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

    5. PD Parameters _Percent change in levels of uNTx/Cr [Day 1 to Day 196]

      Urine samples will be collected for measurement of Urine of AVT03 and Prolia

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
      1. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.
    1. Male subjects who are 18 to 55 years old, inclusive, at the time of signing the ICF.

    2. Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive) at Screening and Day -1.

    Exclusion Criteria:
      1. 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).
    1. Have 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, poor oral hygiene, periodontal, and/or pre-existing dental disease.

    2. Have bone fractures within 6 months prior to Day -1. 4. Have a history of immunodeficiency. 5. Abnormal serum calcium: current hypocalcemia or hypercalcemia at

    Screening or Day -1. Serum calcium levels must be within reference ranges. NOTE:

    Subjects who meet this exclusion at Screening will be allowed to receive supplementation and undergo 1 repeat evaluation, at the discretion of the Investigator.

    1. Known vitamin D deficiency (25[OH]D levels <10 ng/mL [25 nmol/L]) at Screening or Day -1. NOTE: Subjects who meet this exclusion at Screening will be allowed to receive supplementation and undergo 1 repeat evaluation, at the discretion of the Investigator.

    2. Known intolerance to calcium or vitamin D supplements.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Alvotech Swiss AG

    Investigators

    None specified.

    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:
    Nov 19, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 19, 2021