Healthy VolunteersPhase 1NCT05299073
A Study Comparing the Pharmacokinetic Similarity of MB09 and EU/US-Sourced Xgeva
A Phase 1 study testing MB09, US-sourced Xgeva and EU-sourced Xgeva in people with Healthy Volunteers, run by mAbxience Research S.L. at 1 site in Poland.
Trial summary
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, PD, safety and immunogenicity profile of MB09 with EU/US-Xgeva® in healthy male subjects. 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
- Healthy Volunteers
- What is being tested?
- MB09, US-sourced Xgeva and EU-sourced Xgeva
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 257 participants
- Where
- 1 sitePoland
- Study dates
- 1 Mar 2022to 18 Mar 2023
- 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
- The subject is a male of any race, between 28 and 55 years of age, inclusive, at screening.
- The subject has a BMI between 18.5 and 29.9 kg/m2, inclusive, (total body weight between 60 and 95 kg, inclusive) at screening and check-in.
- The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results (congenital nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable), vital sign measurements (systolic BP ≥90 mm Hg and ≤140 mm Hg, diastolic BP ≥50 mm Hg and ≤90 mm Hg), 12 lead ECG results, and physical examination findings at screening and check in.
- The subject must use an adequate method of contraception (eg, condom) or be willing to practice sexual abstinence during the study starting from the day of dosing and for 140 days after dosing. The subject must agree to not donating sperm during the study and for at least 140 days after dosing. Participating subject's female partner of childbearing potential should use an additional form of contraception such as an intra uterine device, barrier method with spermicide, oral contraceptive, injectable progesterone, or sub-dermal implant starting from the male partner's day of dosing until at least 140 days after dosing. The female partner of the participating subject should be familiar with the use of the respective contraceptive methods. Intra-uterine devices and hormonal methods for contraception should be used for at least 1 menstruation cycle prior to the administration of study drug.
- The subject must be able to comprehend and willing to sign an ICF and to abide by the study restrictions. Subjects must have signed an ICF before any study-related procedure or evaluation is performed.
Who cannot join
- The subject has had previous exposure to denosumab.
- The subject has a significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
- The subject has a history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator.
- The subject has any current or recent history of infections, including localised infections (within 2 months prior to screening for any serious infection that requires hospitalisation or IV anti-infective or within 14 days prior to screening for any active infection which requires oral treatment).
- The subject has a dental or jaw disease requiring oral surgery or dental surgery within 6 months prior to study product administration or plans to have dental surgery within 6 months after dosing.
- The subject has a history of osteomyelitis or osteonecrosis of the jaw requiring suturing within 30 days before dosing, or within 30 days after the last study visit.
Show all 18Show fewer
- The subject has a medically significant dental disease or dental neglect, with signs and/or symptoms of local or systemic infection that would likely require a dental procedure during the course of the study. Standard dentistry treatments (eg, dental filling or prophylaxis/cleaning) are allowed.
- The subject has clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to check in, and/or positive urinary test for alcohol or drugs of abuse at screening or check in.
- The subject has positive hepatitis panel (HBV and HCV) or positive HIV test. Subjects whose results are compatible with prior immunisation and not infection may be included at the discretion of the investigator.
- The subject has participated in a clinical study involving administration of an investigational drug (new chemical entity), with dosing in the past 90 days prior to Day 1, or within 5 half-lives of the investigational drug used in the study, whichever is longer.
- The subject has used or intends to use slow-release medications/products considered to still be active within 30 days prior to check in, unless deemed acceptable by the investigator.
- The subject has used or intends to use any nonprescription medications/products (except paracetamol [up to 2 g/day] and ibuprofen [800 mg/day]), including vitamins, minerals, supplements (eg, Biotin), and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check in, unless deemed acceptable by the investigator. Vitamin C, vitamin D, and calcium in daily recommended doses (≤1000 mg elemental calcium and 1000 IU vitamin D based on screening levels of vitamin D) are allowed.
- The subject has received the COVID-19 vaccine within 14 days before Day 1 or plans to receive a COVID-19 vaccine within 12 weeks after study drug dosing or has positive test for COVID 19 during screening or presence of COVID 19 symptoms within 4 weeks prior to Day -1.
- The subject has received a live or attenuated vaccine within 3 months prior to screening or has the intention to receive a vaccine during the study. The subject intends to travel to a region where a vaccination will be required due to endemic disease during the study.
- The subject has used tobacco- or nicotine-containing products within 1 year prior to check-in or anytime during the study, or has a positive cotinine test upon screening or check-in.
- The subject has donated blood within 60 days prior to dosing, plasma from 14 days prior to screening, or platelets from 42 days prior to dosing.
- The subject has poor peripheral venous access.
- Subjects who, in the opinion of the investigator, should not participate in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind, Three-arm, Single-dose, Parallel Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity Profile of MB09 (Denosumab Biosimilar) and EU/US-sourced Xgeva® in Healthy Male Volunteers
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, PD, safety and immunogenicity profile of MB09 with EU/US-Xgeva® in healthy male subjects.
During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Pharmacodynamics, safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.
Read the detailed description
The primary PK parameter endpoints are AUC0-last and Cmax for denosumab. The secondary PK endpoints will include all other PK parameters for denosumab, including AUC0-∞, Tmax, CL and t1/2.
For the primary PK Analysis, an analysis of variance (ANOVA) model with treatment and stratification factors as fixed effects will be performed on the natural log transformed values of Cmax, AUC0 last, and AUC0-∞.
Estimates of geometric mean ratios together with the corresponding 90% confidence intervals (CI) will be derived for the comparisons of the PK parameters as follows:
- MB09 versus EU-Xgeva®
- MB09 versus US-Xgeva®
- EU-Xgeva® versus US-Xgeva®
Bioequivalence will be concluded if the 90% CIs for the test to reference ratios of the geometric least square means for AUC0-last and Cmax are entirely contained within the [80%, 125%] interval.
For the PD Analysis, an analysis of covariance (ANCOVA) model with treatment and stratification factors as fixed effects and logged pre-dose sCTX concentrations fitted as a covariate will be performed on the natural log-transformed values of AUEC0 253 and AUIC0 253.
Adverse events will be coded using MedDRA Version 24. All AE data will be presented in a data listing. Treatment-emergent AEs will be summarised by treatment and overall, as well as by severity and relationship to study drug. Serious AEs and AEs leading to discontinuation of study drug will also be presented in the data listings and summarised by treatment and overall.
The incidence of ADA to denosumab and the neutralizing potential and titre of positive ADAs will be reported. All immunogenicity data will be presented in the data listings.
- Conditions
- Healthy Volunteers
- Being tested
- MB09, US-sourced Xgeva, EU-sourced Xgeva
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB09Drug
Also called denosumab biosimilar
Single dose of 35mg SC administered
US-sourced XgevaDrug
Also called US-licensed Xgeva
Single dose of 35mg SC administered
EU-sourced XgevaDrug
Also called EU-licensed Xgeva
Single dose of 35mg SC administered
| Study group | Role | What they receive |
|---|---|---|
| MB09 (denosumab biosimilar) | Experimental | Sterile vial 120mg/1.7mL, Single dose, 35mg SC Receives: Drug: MB09 |
| US-sourced Xgeva | Active comparator | Sterile vial 120mg/1.7mL, Single dose, 35mg SC Receives: Drug: US-sourced Xgeva |
| EU-sourced Xgeva | Active comparator | Sterile vial 120mg/1.7mL, Single dose, 35mg SC Receives: Drug: EU-sourced Xgeva |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC0-last
Area under the plasma concentration versus time curve from time zero to the last quantifiable concentration
Measured: Day 1 to Day 253
Cmax
Maximum observed plasma concentration
Measured: Day 1 to Day 253
Secondary outcomes (8)
AUC0-∞
Area under the plasma concentration versus time curve from time zero extrapolated to infinity
Measured: Day 1 to Day 253
Tmax
Time to reach Cmax
Measured: Day 1 to Day 253
CL
Clearance
Measured: Day 1 to Day 253
t1/2
Terminal half-life
Measured: Day 1 to Day 253
Pharmacodynamics (sCTX) AUEC0-253
Observed concentration of serum C-terminal telopeptide of Type 1 collagen (sCTX) parameter will be calculated as PD endpoint. AUC0-253: area under the plasma concentration versus time curve from time 0 to day 253
Measured: Day 1 to Day 253
Incidence of Treatment Emergent Adverse Events (TEAEs)
A treatment-emergent adverse event is defined as any event not present before exposure to study drug or any event already present that worsens in intensity or frequency after exposure.
Measured: Day 1 to Day 253
Incidence of Anti-denosumab Antibodies (ADA)
The incidence of ADA to denosumab and the neutralizing potential and titre of positive ADA.
The immunogenicity endpoint included denosumab anti-drug antibodies (ADA).
Measured: Day 1 to Day 253
Incidence of Neutralizing Antibodies (NAb)
The incidence the neutralizing potential and titre of positive ADA.
Measured: Day 1 to Day 253
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2022
- Study start1 Mar 2022
- Primary completion18 Mar 2023
- Study completion18 Mar 2023
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.
- Other trials for 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 257 participants (actual)
Sponsor and investigators
- Lead sponsor
- mAbxience Research S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Monika Tomaszewska-Kiecana, MD, Principal investigator, Biokinetica S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05299073
- Sponsor's protocol ID
- MB09-A-01-19
- Status last verified
- Dec 2024
- First submitted
- 8 Mar 2022
- Last updated
- 3 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Three-arm, Single-dose, Parallel Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity Profile of MB09 (Denosumab Biosimilar) and EU/US-sourced Xgeva® in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT05299073
- Acronym / sponsor ID
- MB09-A-01-19
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 257 participants (actual)
- Lead sponsor
- mAbxience Research S.L.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 18 Mar 2023 (actual)
- Study completion
- 18 Mar 2023 (actual)
- First posted
- 28 Mar 2022 (actual)
- Results
- Posted 3 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, PD, safety and immunogenicity profile of MB09 with EU/US-Xgeva® in healthy male subjects.
During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Pharmacodynamics, safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.
Detailed description
The primary PK parameter endpoints are AUC0-last and Cmax for denosumab. The secondary PK endpoints will include all other PK parameters for denosumab, including AUC0-∞, Tmax, CL and t1/2.
For the primary PK Analysis, an analysis of variance (ANOVA) model with treatment and stratification factors as fixed effects will be performed on the natural log transformed values of Cmax, AUC0 last, and AUC0-∞.
Estimates of geometric mean ratios together with the corresponding 90% confidence intervals (CI) will be derived for the comparisons of the PK parameters as follows:
- MB09 versus EU-Xgeva®
- MB09 versus US-Xgeva®
- EU-Xgeva® versus US-Xgeva®
Bioequivalence will be concluded if the 90% CIs for the test to reference ratios of the geometric least square means for AUC0-last and Cmax are entirely contained within the [80%, 125%] interval.
For the PD Analysis, an analysis of covariance (ANCOVA) model with treatment and stratification factors as fixed effects and logged pre-dose sCTX concentrations fitted as a covariate will be performed on the natural log-transformed values of AUEC0 253 and AUIC0 253.
Adverse events will be coded using MedDRA Version 24. All AE data will be presented in a data listing. Treatment-emergent AEs will be summarised by treatment and overall, as well as by severity and relationship to study drug. Serious AEs and AEs leading to discontinuation of study drug will also be presented in the data listings and summarised by treatment and overall.
The incidence of ADA to denosumab and the neutralizing potential and titre of positive ADAs will be reported. All immunogenicity data will be presented in the data listings.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MB09 (denosumab biosimilar) | Experimental | Drug: MB09Sterile vial 120mg/1.7mL, Single dose, 35mg SC |
| US-sourced Xgeva | Active comparator | Drug: US-sourced XgevaSterile vial 120mg/1.7mL, Single dose, 35mg SC |
| EU-sourced Xgeva | Active comparator | Drug: EU-sourced XgevaSterile vial 120mg/1.7mL, Single dose, 35mg SC |
Who may qualify
- Ages
- 28 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- The subject is a male of any race, between 28 and 55 years of age, inclusive, at screening.
- The subject has a BMI between 18.5 and 29.9 kg/m2, inclusive, (total body weight between 60 and 95 kg, inclusive) at screening and check-in.
- The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results (congenital nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable), vital sign measurements (systolic BP ≥90 mm Hg and ≤140 mm Hg, diastolic BP ≥50 mm Hg and ≤90 mm Hg), 12 lead ECG results, and physical examination findings at screening and check in.
- The subject must use an adequate method of contraception (eg, condom) or be willing to practice sexual abstinence during the study starting from the day of dosing and for 140 days after dosing. The subject must agree to not donating sperm during the study and for at least 140 days after dosing. Participating subject's female partner of childbearing potential should use an additional form of contraception such as an intra uterine device, barrier method with spermicide, oral contraceptive, injectable progesterone, or sub-dermal implant starting from the male partner's day of dosing until at least 140 days after dosing. The female partner of the participating subject should be familiar with the use of the respective contraceptive methods. Intra-uterine devices and hormonal methods for contraception should be used for at least 1 menstruation cycle prior to the administration of study drug.
- The subject must be able to comprehend and willing to sign an ICF and to abide by the study restrictions. Subjects must have signed an ICF before any study-related procedure or evaluation is performed.
Key exclusion criteria (18 listed)
- The subject has had previous exposure to denosumab.
- The subject has a significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
- The subject has a history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator.
- The subject has any current or recent history of infections, including localised infections (within 2 months prior to screening for any serious infection that requires hospitalisation or IV anti-infective or within 14 days prior to screening for any active infection which requires oral treatment).
- The subject has a dental or jaw disease requiring oral surgery or dental surgery within 6 months prior to study product administration or plans to have dental surgery within 6 months after dosing.
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 |
|---|---|---|
| MB09Also: denosumab biosimilarSingle dose of 35mg SC administered | Drug | MB09 (denosumab biosimilar) |
| US-sourced XgevaAlso: US-licensed XgevaSingle dose of 35mg SC administered | Drug | US-sourced Xgeva |
| EU-sourced XgevaAlso: EU-licensed XgevaSingle dose of 35mg SC administered | Drug | EU-sourced Xgeva |
Primary outcome
AUC0-last
Time frame: Day 1 to Day 253
Area under the plasma concentration versus time curve from time zero to the last quantifiable concentration
Cmax
Time frame: Day 1 to Day 253
Maximum observed plasma concentration
8 secondary outcomes
AUC0-∞
Time frame: Day 1 to Day 253
Tmax
Time frame: Day 1 to Day 253
CL
Time frame: Day 1 to Day 253
t1/2
Time frame: Day 1 to Day 253
Pharmacodynamics (sCTX) AUEC0-253
Time frame: Day 1 to Day 253
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: Day 1 to Day 253
Incidence of Anti-denosumab Antibodies (ADA)
Time frame: Day 1 to Day 253
Incidence of Neutralizing Antibodies (NAb)
Time frame: Day 1 to Day 253
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Monika Tomaszewska-Kiecana, MD principal investigator
Biokinetica S.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MB09, US-sourced Xgeva and EU-sourced Xgeva in people with Healthy Volunteers, run by mAbxience Research S.L. at 1 site in Poland.
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 5 inclusion and 18 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 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. 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 3 Jan 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?
AUC0-last (time frame: Day 1 to Day 253). 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?
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 3 Jan 2025.