A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ANX1502 in Normal Healthy Volunteers

• Conditions: antibody-mediated autoimmune indications; 10003816

• Registration Number: NL-OMON53926
• Lead Sponsor: Annexon Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 141

Inclusion Criteria

- Participants who are healthy as determined by medical evaluation including
medical history, physical examination, vital signs assessments (including
supine blood pressure, supine pulse rate, respiration rate, and temporal body
temperature), single 12-lead ECG and laboratory tests.
- [MAD cohorts only] Must be willing to receive vaccinations for encapsulated
bacteria.

Exclusion Criteria

- Clinically significant infection (e.g., viral, bacterial, fungal, or
mycobacterial) within 30*days prior to study intervention that required medical
intervention (not including antibiotic prophylaxis)
- Clinically significant Screening values measured after 5 minutes of rest in a
seated or semi-supine position include:
* Abnormal systolic blood pressure (< 90 or > 140 mmHg).
* Abnormal diastolic blood pressure (< 50 or > 90 mmHg).
* Body temperature (> 38°C).
* Respiration rate at rest (> 20 per minute).
* Clinically significant multiple or severe drug allergies, or severe
post-treatment hypersensitivity reactions
- Has clinically significant laboratory abnormalities (at Screening) including:
* Serum creatinine > upper limit of normal (ULN).
* Estimated creatinine clearance of <80 mL/min as determined by estimated
glomerular ratio [eGFR] (Cockroft Gault).
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory
values > 1.5 x ULN.
* Total bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if
total bilirubin is fractionated and direct bilirubin <35%)
- Known hepatic or biliary abnormalities (except for participants with
Gilbert*s Syndrome who have serum bilirubin < 3 x ULN National Cancer Institute
[NCI] Common Terminology Criteria for Adverse Events [CTCAE v5.0] Grade 2, or
asymptomatic gallstones).
- Has a clinically significant history or presence of ECG findings as judged by
the Principal Investigator (PI) or designee at Screening, including:
* QT interval corrected for heart rate (QTc) >450 msec for male participants or
>470 msec for female participants.
* Abnormal sinus rhythm (heart rate <40 bpm or > 100 bpm).
* Average QRS interval > 120 msec after being confirmed by manual over-read.
* Average PR interval > 220 msec.
* Resting bradycardia (ventricular rate [VR] < 45 beats per minute [bpm]) or
tachycardia (VR > 90 bpm) on Screening ECG.
- An antinuclear antibodies (ANA) titer >= 1:160 at Screening.
- Has donated blood or plasma within 30 days prior to Screening or had a loss
of whole blood of more than 500 mL within the 30 days prior to Screening, or
receipt of a blood transfusion within one year prior to Screening
- Unable to consume a high-fat diet, if selected for the FE part of the study.
- Has experienced symptoms of acute illness or chronic disease within 14 days
prior to Screening, or any disease or condition (medical or surgical) that, by
the determination of the Investigator, might compromise interpretation of
safety or PK data, or would place the participant at risk because of
participation in the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>SAD part: Incidence and severity of treatment emergent adverse events (TEAEs)<br /><br>and clinically significant abnormalities in vital signs, clinical laboratory<br /><br>tests, and electrocardiogram (ECG) after single oral doses.<br /><br><br /><br>MAD part: Incidence and severity of TEAEs and clinically significant<br /><br>abnormalities in vital signs, clinical laboratory tests, and ECGs after<br /><br>multiple doses (over 14 days). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>SAD part:<br /><br>- Plasma ANX1502 and ANX1439 concentrations over time.<br /><br>- ANX1502 and ANX1439 Day 1 plasma PK parameters (e.g., maximum observed plasma<br /><br>concentration [Cmax], observed time to Cmax [Tmax], area under the<br /><br>concentration-time curve [AUCs], terminal half-life [t1/2].<br /><br><br /><br>MAD part:<br /><br>- Plasma ANX1502 and ANX1439 concentrations over time.<br /><br>- ANX1502 and ANX1439 Day 1 and Day 14 plasma PK parameters (e.g., Cmax and<br /><br>Tmax, AUCs and t1/2 minimum observed plasma concentration [Cmin], average<br /><br>observed plasma concentration during multiple-dose administration [Cave],<br /><br>%fluctuation, and accumulation ratio).</p><br>