Ascending Multiple Intravenous Doses of AON-D21 in Healthy Male Subjects.

A Randomized, Single-center, Double-blind, Placebo Controlled Trial With Ascending Multiple Intravenous Doses to Determine Safety, Tolerability and Pharmacokinetics of AON-D21 in Healthy Male Subjects.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AON-D21; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany, 89231
    • Nuvisan GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).
• 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 PK blood sample time point.
• Legal incapacity or limited legal capacity, or incarceration.
• Inability to understand or communicate reliably with the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AON-D21; Multiple ascending doses by iv infusion	Drug: AON-D21; AON-D21 is a PEGylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.
Placebo Comparator: Placebo; Placebo medication identical in appearance to active	Drug: Placebo; Isotonic glucose solution identical in appearance to AON-D21.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Aptarion Biotech AG

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Actual): November 29, 2022
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: S-D21-C200; 2021-006551-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No