Clinical trial NCT05018403: First-in-human Trial With Single-dose C5a-neutralizing AON-D21 in Healthy Male Subjects
Official title: A Randomized, Single-center, Double-blind, Placebo Controlled, First-in-human Trial With Single Ascending Intravenous Doses to Determine Safety, Tolerability and Pharmacokinetics of AON-D21 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Aptarion Biotech AG
Sponsor class: INDUSTRY
First posted: 2021-08-24
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Five groups of participants will be assigned to receive AON-D21 or placebo in ascending dose order. Doses will be escalated based on safety and pharmacokinetic data.
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic parameters after single ascending intravenous doses of AON-D21 in healthy male subjects.

Detailed description: This study will potentially include 5 sequential cohorts with 8 subjects per cohort, then 40 enrolled subjects in total. Within each dose group 6 subjects will be randomized to receive AON-D21 and 2 subjects will be randomly assigned to placebo.

Eligibility criteria: Inclusion Criteria:

* 18 to 55 years of age inclusive, at the time of signing the informed consent.
* Body mass index (BMI) within the range 18 - 30 kg/m2 with a body weight between 50 kg and 120 kg.
* Male subjects
* Subject is healthy as determined by medical evaluation
* Subject provided written informed consent
* Subject is willing to comply with all requirements and restrictions according to the study protocol.

Exclusion Criteria:

* Any concomitant disease, condition, or treatment that could interfere with the conduct of the study.
* Any acquired or congenital immune deficiency.
* Acute infection (including viral infections) in the preceding 6 weeks (8 weeks for respiratory infections).
* Any concomitant disease, condition, or treatment that could interfere with the conduct of the study.
* Any acquired or congenital immune deficiency.
* Acute infection (including viral infections) in the preceding 6 weeks (8 weeks for respiratory infections).
* Clinically relevant abnormality following the Investigator's review of the physical examination, vital signs, ECG and clinical study protocol-defined clinical laboratory tests that, in the opinion of the Investigator, would preclude inclusion in the trial at screening and admission.
* Evidence of COVID-19 signs or symptoms, exposure to infected person or confirmed COVID-19 infection within the last 2 weeks.
* Use of any concomitant medication or prescribed or non-prescribed drugs within 2 weeks or 5 times the half-life, whichever is longer, prior to the first study treatment administration.
* Administration of vaccine(s) within 2 weeks prior to screening or plans to receive such vaccines during the study.
* Use of any investigational drug or participation in any clinical study within 30 days or 5 half-life times, whichever is longer, prior to dosing.
* Positive drug or alcohol screen at screening and admission.
* Any significant blood loss, donated one unit (450 mL) of blood or more, or donated plasma, or received a transfusion of any blood or blood products within 30 days prior to dosing.
* Subjects who are unable to refrain from the consumption of Seville oranges, grapefruit or grapefruit juice and /or pomelos, exotic citrus fruits, grapefruit hybrids, starfruit or fruit juices from 72 hours prior to dosing on Day 1, until completion of the last pharmacokinetic (PK) blood sample time point.
* Legal incapacity or limited legal capacity, or incarceration.
* Inability to understand or communicate reliably with the Investigator.

Primary outcomes:
measure: Primary Safety Endpoint - Overall number of participants with treatment-emergent adverse events (TEAEs) per dosing cohort as assessed by CTCAE.
timeFrame: 14 days.
measure: Primary Safety Endpoint - Per Dosing Cohort number of participants with treatment-emergent adverse events as assessed by CTCAE.
timeFrame: 14 days
Secondary outcomes:
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
measure: Pharmacokinetics of AON-D21.
timeFrame: 14 days.
Other outcomes:
measure: Pharmacodynamics
timeFrame: 14 days
measure: Effects on the complement status
timeFrame: 14 days
measure: To assess potential for immunogenicity of AON-D21
timeFrame: 14 days
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Nuvisan GmbH
name: Manuela Koch, MD
role: PRINCIPAL_INVESTIGATOR
References: