Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000935-30 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AON-D21 | Experimental | Single ascending doses by iv infusion. |
|
| Placebo | Placebo Comparator | Placebo medication identical in appearance to active. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous AON-D21 | Drug | AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary Safety Endpoint - Overall number of participants with treatment-emergent adverse events (TEAEs) per dosing cohort as assessed by CTCAE. | 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. | 14 days. |
| Primary Safety Endpoint - Per Dosing Cohort number of participants with treatment-emergent adverse events as assessed by CTCAE. | Overall number of participants with treatment related treatment-emergent adverse events (TEAEs) as assessed by CTCAE per dosing cohort. | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of AON-D21. | To determine the area under the concentration (AUC)-time curve from 0 to 48 h (AUC0-48). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the area under the concentration (AUC)-time curve from 0 to 72 h (AUC0-72). |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics | To determine the C5a inhibition capacity of AON-D21 by measuring active C5a in blood using a cell-based assay. | 14 days |
| Effects on the complement status | Determining the effect of AON-D21 on levels of C5, C5a, C5b-9 in blood and on the capacity of terminal complement complex formation. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Manuela Koch, MD | Nuvisan GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nuvisan GmbH | Neu-Ulm | 89231 | Germany |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Quadruple: Participant, Investigator, Outcomes Assessor and Care provider.
|
| Intravenous placebo | Drug | Isotonic glucose solution identical in appearance to AON-D21. |
|
|
| 14 days. |
| Pharmacokinetics of AON-D21. | To determine the area under the concentration (AUC)-time curve from 0 to infinity (AUC0-inf). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the maximum concentration (Cmax). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the time of maximum concentration (Tmax). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the half-life (t1/2). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the plasma clearance (CL) calculated as Dose/AUC0-inf. | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the volume of distribution (Vz). | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the amount of AON-D21 excreted (Ae) in urine. | 14 days. |
| Pharmacokinetics of AON-D21. | To determine the renal clearance (CLR) of AON-D21. | 14 days. |
| 14 days |
| To assess potential for immunogenicity of AON-D21 | Determining the presence of anti-drug antibodies (ADA) and anti-peg antibodies in serum. | 14 days |