First-in-human Trial With Single-dose C5a-neutralizing AON-D21 in Healthy Male Subjects

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

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• 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: Yes
• 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).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AON-D21; Single ascending doses by iv infusion.	Drug: Intravenous AON-D21; AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.; Other Names: AON-D21
PLACEBO_COMPARATOR: Placebo; Placebo medication identical in appearance to active.	Drug: Intravenous placebo; Isotonic glucose solution identical in appearance to AON-D21.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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).	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.

Other Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Aptarion Biotech AG

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2021
• Primary Completion (ACTUAL): January 5, 2022
• Study Completion (ACTUAL): January 5, 2022

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (ACTUAL): August 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: S-D21-C100; 2021-000935-30 (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