HealthyPhase 1NCT04850339
First in Human Study of ANXV (Recombinant Human Annexin A5) in Healthy Volunteers
A Phase 1 study testing ANXV in people with Healthy, run by Annexin Pharmaceuticals AB at 1 site in Netherlands.
Trial summary
This is an adaptive, randomised, double-blind, single-centre, placebo-controlled phase I, First in Human study designed to evaluate the safety, tolerability and pharmacokinetics of single and multiple intravenous dosing of ANXV in healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- ANXV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Dec 2020to 27 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to give written informed consent for participation in the study.
- Healthy male subject aged 18-50 years inclusive at screening.
- BMI ≥ 18.0 and ≤ 30.0 kg/m2 and weight at least 50 kg and no more than 100 kg at screening.
- Overtly healthy based on medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm from the date of dosing until 3 months after (last) dosing with the IMP. Their female partner of child-bearing potential are expected to use contraceptive methods with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]).
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
- Any planned major surgery within the duration of the study.
- Any positive result on screening for serum hepatitis B surface antigen (HbsAg), hepatitis C antibody and Human Immunodeficiency Virus (HIV).
- History of thromboembolic events.
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- History of significant bleeding (gross haematuria, haemoptysis, gastrointestinal tract bleeding).
- Evidence or history of a hypercoagulable state (e.g. shortened APTT).
- Prior exposure to recombinant Annexin A5 (for diagnostic purposes).
- Any history of coronary artery disease or cerebrovascular accident.
- Known cardiac disease, cardiac anomaly or cardiac deformity.
- Known heredity for autoimmune disease with described presence of potentially pathogenic Annexin A5 antibodies, e.g. antiphospholipid syndrome, systemic lupus erythematosus or systemic sclerosis, as judged by the Investigator.
- Any history of or active peptic ulcer disease.
- Any clinically significant disease affecting the respiratory tract (e.g. obstructive and restrictive respiratory disease, chronic respiratory disease such as alveolitis, inflammatory respiratory disease, autoimmune respiratory disease, present respiratory infections, pulmonary vascular disease) that would influence the results of the study or the subject's ability to participate in the study, as judged by the Investigator.
- eGFR (based on plasma-creatinine) outside of normal range at screening or known renal impairment (≤70 mL/min).
- Vaccination with live-attenuated vaccines within 4 weeks of the screening visit.
- After 5 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
- Systolic blood pressure <90 or >140 mmHg, or
- Diastolic blood pressure <40 or >90 mmHg, or
- Pulse <40 or >100 bpm
- Current evidence or history of bacterial, viral or fungal infections within 7 days before (first) IMP administration as judged by the Investigator.
- Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to ANXV.
- Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within two weeks prior to the (first) administration of IMP, except occasional intake of paracetamol (maximum 2,000 mg/day; and not exceeding 3,000 mg/week), at the discretion of the Investigator and nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
- Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Subjects consented and screened but not dosed in previous phase I studies are not excluded.
- Current smokers or users of nicotine products. Smokers that stopped smoking <3 months prior to screening.
- Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.
- History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- Presence or history of drug abuse, as judged by the Investigator.
- History of, or current use of, anabolic steroids.
- Excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages.
- Intake of xanthine and/or taurine containing energy drinks within 2 days prior to screening.
- Plasma donation within one month of screening or blood donation (or corresponding blood loss) of >450 ml during the three months prior to screening.
- Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements, or unfit for participation for any other reason.
- Previous confirmed COVID-19 disease requiring hospital care or positive COVID-19 test on admission to the clinic.
- Insufficient venous access for study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple Dose First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ANXV Administered as an Intravenous Infusion to Healthy Male Subjects
This is an adaptive, randomised, double-blind, single-centre, placebo-controlled phase I, First in Human study designed to evaluate the safety, tolerability and pharmacokinetics of single and multiple intravenous dosing of ANXV in healthy male subjects.
Read the detailed description
This First in Human study is divided in two parts. Part I, Single Ascending Dose (SAD), will explore safety, tolerability and PK of single intravenous doses of ANXV. Part II, Multiple Ascending Dose (MAD), will explore safety, tolerability and PK of multiple doses (five consecutive daily doses) of intravenous ANXV.
The objectives of this study are:
Primary objective:
- To evaluate the safety and tolerability of single/multiple ascending doses of ANXV in healthy male subjects.
Secondary objective:
- To determine the PK profile of single/multiple ascending doses of ANXV in healthy male subjects.
Exploratory objectives:
- To evaluate ADA to ANXV and other relevant parameters.
- Conditions
- Healthy
- Being tested
- ANXV, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANXVBiological
Intravenous infusion
PlaceboOther
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| ANXV single dose | Active comparator | ANXV in a single ascending dose pattern in four dose levels. Receives: Biological: ANXV |
| Placebo single dose | Placebo comparator | Placebo in a single ascending dose pattern in four dose levels. Receives: Other: Placebo |
| ANXV multiple dose | Active comparator | ANXV in a multiple ascending dose pattern in three dose levels. Receives: Biological: ANXV |
| Placebo multiple dose | Placebo comparator | Placebo in a multiple ascending dose pattern in four dose levels. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of adverse events.
Frequency of adverse events at single and multiple ascending doses of ANXV.
Measured: From day 1 (inclusion) until day 35
Seriousness of adverse events.
Seriousness of adverse events at single and multiple ascending doses of ANXV.
Measured: From day 1 (inclusion) until day 35
Intensity of adverse events.
Intensity of adverse events at single and multiple ascending doses of ANXV.
Measured: From day 1 (inclusion) until day 35
Secondary outcomes (8)
PK profile of single and multiple ascending doses of ANXV: AUClast
AUC from time zero to time of last quantifiable analyte concentration (AUClast)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Cmax
Observed maximum concentration (Cmax)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Tmax
Time to Cmax (Tmax)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: λz
Terminal slope of a semi-logarithmic concentration-time curve (λz)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: T½
Terminal half life (T½)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: CL
Clearance (CL)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Vz
Volume of distribution (Vz)
Measured: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Fraction excreted in urine (fe)
Fraction excreted in urine (fe)
Measured: 0-24hours after IMP administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2021
- Study start21 Dec 2020
- Primary completion27 Oct 2021
- Study completion27 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annexin Pharmaceuticals AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anna Frostegård, MD, PhD, Study director, Annexin Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04850339
- Sponsor's protocol ID
- ANN-001
- Status last verified
- May 2022
- First submitted
- 4 Mar 2021
- Last updated
- 16 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple Dose First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ANXV Administered as an Intravenous Infusion to Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT04850339
- Acronym / sponsor ID
- ANN-001
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Annexin Pharmaceuticals ABIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 27 Oct 2021 (actual)
- Study completion
- 27 Oct 2021 (actual)
- First posted
- 20 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an adaptive, randomised, double-blind, single-centre, placebo-controlled phase I, First in Human study designed to evaluate the safety, tolerability and pharmacokinetics of single and multiple intravenous dosing of ANXV in healthy male subjects.
Detailed description
This First in Human study is divided in two parts. Part I, Single Ascending Dose (SAD), will explore safety, tolerability and PK of single intravenous doses of ANXV. Part II, Multiple Ascending Dose (MAD), will explore safety, tolerability and PK of multiple doses (five consecutive daily doses) of intravenous ANXV.
The objectives of this study are:
Primary objective:
- To evaluate the safety and tolerability of single/multiple ascending doses of ANXV in healthy male subjects.
Secondary objective:
- To determine the PK profile of single/multiple ascending doses of ANXV in healthy male subjects.
Exploratory objectives:
- To evaluate ADA to ANXV and other relevant parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ANXV single dose | Active comparator | Biological: ANXVANXV in a single ascending dose pattern in four dose levels. |
| Placebo single dose | Placebo comparator | Other: PlaceboPlacebo in a single ascending dose pattern in four dose levels. |
| ANXV multiple dose | Active comparator | Biological: ANXVANXV in a multiple ascending dose pattern in three dose levels. |
| Placebo multiple dose | Placebo comparator | Other: PlaceboPlacebo in a multiple ascending dose pattern in four dose levels. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Willing and able to give written informed consent for participation in the study.
- Healthy male subject aged 18-50 years inclusive at screening.
- BMI ≥ 18.0 and ≤ 30.0 kg/m2 and weight at least 50 kg and no more than 100 kg at screening.
- Overtly healthy based on medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm from the date of dosing until 3 months after (last) dosing with the IMP. Their female partner of child-bearing potential are expected to use contraceptive methods with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]).
Key exclusion criteria (36 listed)
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
- Any planned major surgery within the duration of the study.
- Any positive result on screening for serum hepatitis B surface antigen (HbsAg), hepatitis C antibody and Human Immunodeficiency Virus (HIV).
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 |
|---|---|---|
| ANXVIntravenous infusion | Biological | ANXV multiple dose, ANXV single dose |
| PlaceboIntravenous infusion | Other | Placebo multiple dose, Placebo single dose |
Primary outcome
Frequency of adverse events.
Time frame: From day 1 (inclusion) until day 35
Frequency of adverse events at single and multiple ascending doses of ANXV.
Seriousness of adverse events.
Time frame: From day 1 (inclusion) until day 35
Seriousness of adverse events at single and multiple ascending doses of ANXV.
Intensity of adverse events.
Time frame: From day 1 (inclusion) until day 35
Intensity of adverse events at single and multiple ascending doses of ANXV.
8 secondary outcomes
PK profile of single and multiple ascending doses of ANXV: AUClast
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Cmax
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Tmax
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: λz
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: T½
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: CL
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Vz
Time frame: 0-24hours after IMP administration
PK profile of single and multiple ascending doses of ANXV: Fraction excreted in urine (fe)
Time frame: 0-24hours after IMP administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2022.
- 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.
Anna Frostegård, MD, PhD study director
Annexin Pharmaceuticals
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 ANXV in people with Healthy, run by Annexin Pharmaceuticals AB at 1 site in Netherlands.
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 36 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 16 May 2022. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Frequency of adverse events. (time frame: From day 1 (inclusion) until day 35). The study lists 3 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 16 May 2022.