PrimarySAD: - To evaluate the safety and tolerability of single ascending doses of ANX1502 in healthy participants.MAD: - To evaluate the safety and tolerability of multiple ascending doses of ANX1502 in healthy participants.SecondarySAD: - To…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
SAD part: Incidence and severity of treatment emergent adverse events (TEAEs)
and clinically significant abnormalities in vital signs, clinical laboratory
tests, and electrocardiogram (ECG) after single oral doses.
MAD part: Incidence and severity of TEAEs and clinically significant
abnormalities in vital signs, clinical laboratory tests, and ECGs after
multiple doses (over 14 days).
Secondary outcome
SAD part:
- Plasma ANX1502 and ANX1439 concentrations over time.
- ANX1502 and ANX1439 Day 1 plasma PK parameters (e.g., maximum observed plasma
concentration [Cmax], observed time to Cmax [Tmax], area under the
concentration-time curve [AUCs], terminal half-life [t1/2].
MAD part:
- Plasma ANX1502 and ANX1439 concentrations over time.
- ANX1502 and ANX1439 Day 1 and Day 14 plasma PK parameters (e.g., Cmax and
Tmax, AUCs and t1/2 minimum observed plasma concentration [Cmin], average
observed plasma concentration during multiple-dose administration [Cave],
%fluctuation, and accumulation ratio).
Background summary
Annexon is developing drugs that target complement component 1 complex
(specifically, components C1q and C1s) in order to inhibit the activity of the
classical complement pathway. The classical complement cascade is a part of the
innate immune system that plays a significant role in the clearance of invading
pathogens. The initiating molecule of the classical cascade is C1q which
undergoes conformational change upon binding its target, resulting in
activation of C1s protease and initiation of the rest of the classical
complement cascade.
ANX1502 is a small molecule prodrug of ANX1439 which targets activated C1s
serine protease. In vivo, and ANX1502 is rapidly converted to the
pharmacologically active agent ANX1439, which as mentioned targets activated
C1s thus inhibiting classical complement activation. ANX1439 does not affect
complement activation through the lectin and alternate pathways, leaving the
broader complement response intact.
The overall clinical development objective is to demonstrate the safety,
tolerability, and efficacy of ANX1502 as a potential oral treatment of for
antibody-mediated autoimmune diseases where complement activation is implicated
in disease pathology.
Study objective
Primary
SAD:
- To evaluate the safety and tolerability of single ascending doses of ANX1502
in healthy participants.
MAD:
- To evaluate the safety and tolerability of multiple ascending doses of
ANX1502 in healthy participants.
Secondary
SAD:
- To determine the single-dose pharmacokinetic (PK) profiles of ANX1502
(prodrug) and ANX1439 (active) in healthy participants
- To determine the effect of a high-fat meal (fed) on the PK profiles of
ANX1502 and ANX1439 following a single dose of ANX1502 in healthy participants
MAD:
- To determine the steady-state PK profiles of ANX1502 (prodrug) and ANX1439
(active) in healthy participants
Study design
A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending
Dose Study
Intervention
ANX1502 or matching placebo
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the overall benefit risk in the CSP
for further information.
Sierra point Pkwy, Building C, 2nd Floor 1400
Brisbane CA 94005
US
Sierra point Pkwy, Building C, 2nd Floor 1400
Brisbane CA 94005
US
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-000594-21-NL |
| ClinicalTrials.gov | NCT05521269 |
| CCMO | NL80646.056.22 |