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

NCT05018403 | Completed Phase 1 DMC

• 2 other identifiers: S-D21-C1002021-000935-30
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Pharmacokinetics of AON-D21.

  14 days.

• Pharmacokinetics of AON-D21.

  14 days.

• Pharmacokinetics of AON-D21.

  14 days.

• Pharmacokinetics of AON-D21.

  14 days.

• Pharmacokinetics of AON-D21.

  14 days.

Other Outcomes (3)

• Pharmacodynamics

  14 days

• Effects on the complement status

  14 days

• To assess potential for immunogenicity of AON-D21

  14 days

Study Arms (2)

AON-D21

EXPERIMENTAL

Single ascending doses by iv infusion.

Drug: Intravenous AON-D21

Placebo

PLACEBO COMPARATOR

Placebo medication identical in appearance to active.

Drug: Intravenous placebo

Interventions

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.

Also known as: AON-D21

AON-D21

Intravenous placebo DRUG

Isotonic glucose solution identical in appearance to AON-D21.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Aptarion Biotech AG: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Study Officials

• Manuela Koch, MD

  Nuvisan GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple: Participant, Investigator, Outcomes Assessor and Care provider.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 24, 2021
• Study Start: August 3, 2021
• Primary Completion: January 5, 2022
• Study Completion: January 5, 2022
• Last Updated: January 12, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)