This is a Phase I Study Conducted in Healthy VolunteersPhase 1NCT05876949
AVT03 With Xgeva in Healthy Male Subjects
A Phase 1 study testing AVT03 and Denosumab in people with This is a Phase I Study Conducted in Healthy Volunteers, run by Alvotech Swiss AG at 3 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 28 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- This is a Phase I Study Conducted in Healthy Volunteers
- What is being tested?
- AVT03 and Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 21 Jul 2023to 15 Apr 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- Male subjects who are 28 to 55 years old, inclusive, at the time of signing the ICF.
- 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.
Who cannot join
- 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.
- 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.
- Have bone fractures, presence of active healing fractures, or recent bone fracture
- Abnormal serum calcium.
- Known vitamin D deficiency.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
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
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
Read the 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.
- Being tested
- AVT03, Denosumab
- Keywords
- Denosumab, Healthy Volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVT03Biological
Also called AVT03 proposed Biosimilar to Denosumab
AVT03 will be given as 1 time subcutaneous injection
DenosumabBiological
Also called Xgeva
Xgeva (denosumab) will be given as 1 time subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm AVT03 120mg | Experimental | AVT03 is the proposed biosimilar for Xgeva (denosumab). Subjects in this arm will receive a single 120mg dose of AVT03 as a subcutaneous injection Receives: Biological: AVT03 |
| Active Comparator Xgeva 120mg | Active comparator | Xgeva (denosumab) is the proposed active comparator for AVT03. Subjects in this arm will receive a single 120mg dose of Xgeva (denosumab) as a subcutaneous injection Receives: Biological: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Co-primary PK Endpoint Cmax: Maximum Serum Concentration
Samples will be collected for measurement
Measured: 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
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
Samples will be collected for measurement
Measured: 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 (3)
PK_ AUC0-inf: Comprised of AUC0-t and AUC Extrapolated From Time t to Time Infinity.
Samples will be collected for measurement
Measured: 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
Safety Incidence, Nature and Severity of Adverse Events.
Measured: Day 1(week 1) to Day 196 (week 28)]
Immunogenicity Presence of ADAs and Presence of nAbs Against AVT03 and Xgeva
Samples will be collected for measurement
Measured: Day 1, Day 8, Day 15, Day 29, Day 57, Day 71, Day 112, Day 141, Day 196/EoS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start21 Jul 2023
- Primary completion15 Apr 2024
- Study completion15 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for This is a Phase I Study Conducted in Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alvotech Swiss AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Felicitas Bullo, Study director, Alvotech Swiss AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05876949
- Sponsor's protocol ID
- AVT03-GL-P03
- Status last verified
- Apr 2025
- First submitted
- 17 May 2023
- Last updated
- 15 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tomaszewska-Kiecana M, Bullo F, Jaskiewicz L, Stamatakos S, Otto H, Rai M, Sattar A, Leutz S, Berti F. A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults. Expert Opin Investig Drugs. 2025 Jun;34(6):539-546. doi: 10.1080/13543784.2025.2505469. Epub 2025 May 16.
PubMed 40357869
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05876949
- Acronym / sponsor ID
- AVT03-GL-P03
- Keywords
- Denosumab, Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- Alvotech Swiss AGIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2023 (actual)
- Primary completion
- 15 Apr 2024 (actual)
- Study completion
- 15 Apr 2024 (actual)
- First posted
- 26 May 2023 (actual)
- Results
- Posted 15 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm AVT03 120mg | Experimental | Biological: AVT03AVT03 is the proposed biosimilar for Xgeva (denosumab). Subjects in this arm will receive a single 120mg dose of AVT03 as a subcutaneous injection |
| Active Comparator Xgeva 120mg | Active comparator | Biological: DenosumabXgeva (denosumab) is the proposed active comparator for AVT03. Subjects in this arm will receive a single 120mg dose of Xgeva (denosumab) as a subcutaneous injection |
Who may qualify
- Ages
- 28 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
- Male subjects who are 28 to 55 years old, inclusive, at the time of signing the ICF.
- 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.
Key exclusion criteria (5 listed)
- 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.
- 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.
- Have bone fractures, presence of active healing fractures, or recent bone fracture
- Abnormal serum calcium.
- Known vitamin D deficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVT03Also: AVT03 proposed Biosimilar to DenosumabAVT03 will be given as 1 time subcutaneous injection | Biological | Experimental Arm AVT03 120mg |
| DenosumabAlso: XgevaXgeva (denosumab) will be given as 1 time subcutaneous injection | Biological | Active Comparator Xgeva 120mg |
Primary outcome
Co-primary PK Endpoint Cmax: Maximum Serum Concentration
Time frame: 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
Samples will be collected for measurement
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
Time frame: 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
Samples will be collected for measurement
3 secondary outcomes
PK_ AUC0-inf: Comprised of AUC0-t and AUC Extrapolated From Time t to Time Infinity.
Time frame: 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
Safety Incidence, Nature and Severity of Adverse Events.
Time frame: Day 1(week 1) to Day 196 (week 28)]
Immunogenicity Presence of ADAs and Presence of nAbs Against AVT03 and Xgeva
Time frame: Day 1, Day 8, Day 15, Day 29, Day 57, Day 71, Day 112, Day 141, Day 196/EoS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40357869Tomaszewska-Kiecana M, Bullo F, Jaskiewicz L, Stamatakos S, Otto H, Rai M, Sattar A, Leutz S, Berti F. A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults. Expert Opin Investig Drugs. 2025 Jun;34(6):539-546. doi: 10.1080/13543784.2025.2505469. Epub 2025 May 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Felicitas Bullo study director
Alvotech Swiss AG
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AVT03 and Denosumab in people with This is a Phase I Study Conducted in Healthy Volunteers, run by Alvotech Swiss AG at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Poland, South Africa, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Co-primary PK Endpoint Cmax: Maximum Serum Concentration (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05876949, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.