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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-006551-33 | EudraCT Number |
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The main purpose of this study is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic parameters after multiple ascending intravenous doses of AON-D21 in healthy male subjects.
This study will potentially include 2 two sequential cohorts with 8 healthy male subjects per cohort, then 16 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AON-D21 | Experimental | Multiple ascending doses by iv infusion |
|
| Placebo | Placebo Comparator | Placebo medication identical in appearance to active |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Nature, occurrence, and severity of treatment-emergent adverse events. | 27 days |
| Per dosing cohort number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0. | Overall number of participants with treatment related treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 per dosing cohort. | 27 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics assessment | Area under the concentration-time curve (AUC) over the dosing interval at steady state (AUC0-tau) of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Maximum concentration at steady state (Cmax) of AON-D21 in plasma. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Manuela Koch, MD | Nuvisan GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nuvisan GmbH | Neu-Ulm | 89231 | Germany |
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Sequential: Two groups of participants will be assigned to receive AON-D21 or placebo in ascending dose order. Dose will be escalated based on safety and pharmacokinetic data.
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Quadruple: Participant, Investigator, Outcomes Assessor and Care provider.
| Placebo | Drug | Isotonic glucose solution identical in appearance to AON-D21. |
|
| 27 days |
| Pharmacokinetics assessment | Average drug concentration at steady state (Cav) of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Trough concentrations (Ctrough) of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Time of maximum concentration at steady state (Tmax) of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Terminal half-life at steady state (t1/2) of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Accumulation ratios for Cmax and AUC of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Clearance (CL) of AON-D21 in plasma at steady state. | 27 days |
| Pharmacokinetics assessment | Volume of distribution (Vz) of AON-D21 in plasma at steady state. | 27 days |
| Pharmacokinetics assessment | AUC from 0 to 48 hours (AUC0-48) after the first dose of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | AUC from 0 extrapolated to infinity (AUC0-inf) after the first dose of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Maximum concentration (Cmax) after the first dose of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Time to maximum concentration (Tmax) after the first dose of AON-D21 in plasma. | 27 days |
| Pharmacokinetics assessment | Terminal half life (t1/2) after the first dose of AON-D21 in plasma. | 27 days |
| Pharmacodynamics assessment | Measurement of concentration of C5 in plasma. | 27 days |
| Pharmacodynamics assessment | Measurement of concentration of C5a in plasma. | 27 days |
| Pharmacodynamics assessment | Measurement of concentration of C5b-9 in plasma. | 27 days |
| Pharmacodynamics assessment | Qualitative assessment of terminal complement complex (TCC) formation in plasma. | 27 days |
| To assess potential for immunogenicity | Measurement of anti-drug antibodies (ADA) in plasma. | 27 days |
| To assess potential for immunogenicity | Measurement of anti-polyethylene glycol (PEG) antibodies in plasma. | 27 days |