Healthy
Conditions
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.
Interventions
DRUGIntravenous AON-D21
AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.
DRUGIntravenous placebo
Isotonic glucose solution identical in appearance to AON-D21.
Sponsors
Aptarion Biotech AG
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple: Participant, Investigator, Outcomes Assessor and Care provider.
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint - Overall number of participants with treatment-emergent adverse events (TEAEs) per dosing cohort as assessed by CTCAE. | 14 days. | To determine the overall safety and tolerability of AON-D21 by analyzing number of participants with treatment-related adverse events as assessed by CTCAE. Nature, occurrence, and severity of treatment-emergent adverse events. |
| Primary Safety Endpoint - Per Dosing Cohort number of participants with treatment-emergent adverse events as assessed by CTCAE. | 14 days | Overall number of participants with treatment related treatment-emergent adverse events (TEAEs) as assessed by CTCAE per dosing cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of AON-D21. | 14 days. | To determine the area under the concentration (AUC)-time curve from 0 to 48 h (AUC0-48). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics | 14 days | To determine the C5a inhibition capacity of AON-D21 by measuring active C5a in blood using a cell-based assay. |
| Effects on the complement status | 14 days | Determining the effect of AON-D21 on levels of C5, C5a, C5b-9 in blood and on the capacity of terminal complement complex formation. |
| To assess potential for immunogenicity of AON-D21 | 14 days | Determining the presence of anti-drug antibodies (ADA) and anti-peg antibodies in serum. |
Countries
Germany
Outcome results
None listed