First in Human Study of ANXV (Recombinant Human Annexin A5) in Healthy Volunteers

NCT04850339 | Completed Phase 1 DMC

• 1 other identifier: ANN-001
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Frequency of adverse events.

  Frequency of adverse events at single and multiple ascending doses of ANXV.

  From day 1 (inclusion) until day 35

• Seriousness of adverse events.

  Seriousness of adverse events at single and multiple ascending doses of ANXV.

  From day 1 (inclusion) until day 35

• Intensity of adverse events.

  Intensity of adverse events at single and multiple ascending doses of ANXV.

  From day 1 (inclusion) until day 35

Secondary Outcomes (8)

• PK profile of single and multiple ascending doses of ANXV: AUClast

  0-24hours after IMP administration

• PK profile of single and multiple ascending doses of ANXV: Cmax

  0-24hours after IMP administration

• PK profile of single and multiple ascending doses of ANXV: Tmax

  0-24hours after IMP administration

• PK profile of single and multiple ascending doses of ANXV: λz

  0-24hours after IMP administration

• PK profile of single and multiple ascending doses of ANXV: T½

  0-24hours after IMP administration

Study Arms (4)

ANXV single dose

ACTIVE COMPARATOR

ANXV in a single ascending dose pattern in four dose levels.

Biological: ANXV

Placebo single dose

PLACEBO COMPARATOR

Placebo in a single ascending dose pattern in four dose levels.

Other: Placebo

ANXV multiple dose

ACTIVE COMPARATOR

ANXV in a multiple ascending dose pattern in three dose levels.

Biological: ANXV

Placebo multiple dose

PLACEBO COMPARATOR

Placebo in a multiple ascending dose pattern in four dose levels.

Other: Placebo

Interventions

ANXV BIOLOGICAL

Intravenous infusion

ANXV multiple dose; ANXV single dose

Placebo OTHER

Intravenous infusion

Placebo multiple dose; Placebo single dose

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 \[IUS\]).

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Annexin Pharmaceuticals AB: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713, Netherlands

Location

Study Officials

• Anna Frostegård, MD, PhD

  Annexin Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: April 20, 2021
• Study Start: December 21, 2020
• Primary Completion: October 27, 2021
• Study Completion: October 27, 2021
• Last Updated: May 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)