The main purposes of this study are:
* to investigate the safety and tolerability of ACI-19764 when it is administered to healthy participants and participants with cardiovascular risk factors * to determine how quickly and to what extent ACI-19764 is absorbed, transported, metabolized, and excreted by the body (fasted and after a meal) * to determine the effect of ACI-19764 on specific markers in the blood that are part of the immune system
The effects of ACI-19764 will be compared with the effects of a placebo. ACI-19764 is a brain-penetrant NLRP3 inhibitor.
The study consists of 3 parts, Part A (SAD, single ascending dose) and Part B (MAD, multiple ascending doses) in healthy participants, and Part C (one multiple-dose level) in participants with cardiovascular risk factors. Participants in Part A will receive the study compound once, and participants in Part B and Part C will receive the study compound multiple times (daily over 14 and 28 days, respectively). Parts A and B will be divided into different groups of participants to test different doses of ACI-19764.
Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
Healthy male (Parts A and B) or female (Part B) aged between 18 and 65 years (inclusive) at screening or, male or female with cardiovascular risk factors between 18 and 75 years (inclusive) (Part C).
For Parts A and B: Body mass index of 18.0 to 29.9 kg/m2 (inclusive) at screening.
For Part C: Presence of either obesity (defined as a BMI of 30.0-42.0 kg/m2 inclusive) and/or existing diagnosis of well controlled type II diabetes (with HbA1c >6.5% or 48 mmol/mol and ≤8.5% or 69 mmol/mol) (for participants with diabetes the BMI can range between 18.0-42.0 kg/m2 inclusive).
Known hypersensitivity to any excipient of the ACI-19764 formulations.
Known clinically relevant hypersensitivity or allergy to any therapeutic treatment (including non-steroidal anti-inflammatory drugs [NSAIDs], or nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 [NLRP3] inhibitors), vaccines, cosmetics, natural rubber or latex and/or food.
Clinically relevant findings on the physical examination at screening or on Day -1.
Clinically relevant findings in clinical laboratory tests
Parallel
Placebo
DrugPlacebo capsules matching ACI-19764 capsules
ACI-19764 at dose A1
DrugACI-19764 capsules at dose A1
ACI-19764 at dose A2
DrugACI-19764 capsules at dose A2
ACI-19764 at dose A3
DrugACI-19764 capsules at dose A3
ACI-19764 at dose A4
DrugACI-19764 capsules at dose A4
ACI-19764 at dose A5
DrugACI-19764 capsules at dose A5
ACI-19764 at dose A6
DrugACI-19764 capsules at dose A6
ACI-19764 at dose B1
DrugACI-19764 capsules at dose B1
ACI-19764 at dose B2
DrugACI-19764 capsules at dose B2
ACI-19764 at dose B3
DrugACI-19764 capsules at dose B3
ACI-19764 at dose C1
DrugACI-19764 capsules at dose C1
13
Treatment groupsSee each treatment group below.
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely related, possibly related or probably related)
Vital signs: Change from baseline in blood pressure
Vital signs: Change from baseline in respiratory rate
Vital signs: Change from baseline in pulse rate
Pharmacokinetic (PK) in plasma: Maximum observed concentration (Cmax) in fed state
Applicable to study Part A Food Effect group only
Pharmacokinetic (PK) in plasma: Time to reach Cmax (tmax) in fed state
Applicable to study Part A Food Effect group only
Pharmacokinetic (PK) in plasma: Area under the curve (AUC) from time zero to the last measured concentration above the limit of quantification (AUC 0-last), in fed state
Applicable to study Part A Food Effect group only
Pharmacokinetic (PK) in plasma: AUC from time zero to infinity (AUC 0-infinity) in fed state
Applicable to study Part A Food Effect group only
Click on the lead sponsor to view all of their trials.
AC Immune SA
Lead sponsor
ICON Clinical Research
Collaborator
