A study to assess the safety and tolerability of ACI-3024 and how the drug affects and interacts with the body

ISRCTN	ISRCTN18150742
DOI	https://doi.org/10.1186/ISRCTN18150742
EudraCT/CTIS number	2019-001567-73
Secondary identifying numbers	ACI-3024-1901

Submission date: 01/03/2021
Registration date: 30/03/2021
Last edited: 01/04/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Alzheimer’s disease is the most common cause of dementia. Dementia includes symptoms of memory loss and difficulties with thinking speed, understanding, judgement, or language. People with Alzheimer’s disease may also experience changes in mood and difficulties doing daily activities.

ACI-3024 is an investigational drug developed against Alzheimer’s disease. There are currently no effective treatments for this condition. It is hoped that the study drug will be more effective than the treatments currently available and have a positive impact for patients with Alzheimer’s disease.

This study is the first time the study drug is being given to humans. The study aims to collect information the safety of the study drug and any side effects that may be associated with it; how much of the study drug and its breakdown products get into the bloodstream, urine, and the fluid of the brain and spinal cord; how food, sex, age, and ethnicity affect how the body breaks down and removes the study drug from the body; and how the study drug affects biomarkers of Alzheimer’s disease in blood (a biomarker is something found in the blood, other body fluids, or body tissues that can be used to measure the progress of a disease or the effects of a treatment).

Who can participate?
Healthy volunteers aged between 20 and 80 years.

What does the study involve?
Up to 80 participants will be taking part in this study, which consists of 2 main parts. In part one, several cohorts of healthy volunteers will receive increasing doses of ACI-3024 on one single occasion. In part two, several cohorts of healthy volunteers will receive increasing doses of ACI-3024 for several days.

What are the possible benefits and risks of participating?
No benefits are expected from participation in the study.

The study drug may have side effects that are currently unknown. There is a remote chance that the study drug (and indeed any drug product) may cause an allergic reaction, which in some cases may be adverse. This is known as an anaphylactic reaction. Symptoms of an anaphylactic reaction include sudden shortness of breath, decreased consciousness, and rash. An anaphylactic reaction may require emergency treatment. In order to monitor participants’ health during the study, regular checks of blood pressure, body temperature, and heart (by ECG) will be performed. Blood samples will be regularly taken to check the liver, kidney and other organs are functioning normally.

Where is the study run from?
Covance Clinical Research Unit Ltd (UK)

When is the study starting and how long is it expected to run for?
From February 2019 to August 2020

Who is funding the study?
AC Immune (Switzerland

Who is the main contact?
clinicaltrials@acimmune.com

Contact information

Dr Hliva Valérie
Scientific

AC Immune SA
EPFL Innovation Park
Lausanne
1015
Switzerland

ORCID ID	0000-0002-1252-0033
Phone	+41 21 345 93 34
Email	valerie.hliva@acimmune.com

Dr Hliva Valérie
Public

AC Immune SA
EPFL Innovation Park
Lausanne
1015
Switzerland

Phone	+41 21 345 91 21
Email	clinicaltrials@acimmune.com

Study information

Study design	Double-blind randomized placebo-controlled sequential single dose and multiple ascending dose (SAD/MAD) study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	No participant information sheet available
Scientific title	A first-in-human, randomized, placebo-controlled, double-blind, sequential single and multiple ascending dose (SAD/MAD) study with open-label food effect and pharmacodynamic assessment arms to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACI-3024
Study acronym	ACI-3024-1901
Study objectives	To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACI-3024
Ethics approval(s)	Approved 31/05/2019, London - Brent Research Ethics Committee (80 London Road, Skipton House, London, SE1 6LH; +44 (0)20 7104 8222; nrescommittee.london-brent@nhs.net), ref: 19/LO/0617
Health condition(s) or problem(s) studied	Alzheimer Disease
Intervention	Participants will be randomly allocated to one of the 4 arms of the study: 1. Single ascending doses oral intake with ACI-3024 2. Single dose oral intake with placebo 3. Multiple ascending doses oral intake with ACI-3024 4. Multiple doses oral intake with placebo The study is made of 2 subsequent parts. In part 1, the single ascending dose part, 5 cohorts of 8 subjects will participate. In each cohort, subjects will be randomly assigned to the active (ACI-3024, 6 subjects) or placebo arm (2 subjects). Doses of ACI-3024 will be increasing doses. Participants will swallow a suspension of ACI-3024 or placebo (liquid used for suspension) once during their participation. In part 2, the multiple ascending dose part, 4 cohorts of 10 subjects will participate. In each cohort, subjects will be randomly assigned to the active (ACI-3024, 8 subjects) or placebo arm (2 subjects). Doses of ACI-3024 will be using doses already tested in part 1. Participants will swallow a suspension of ACI-3024 or placebo (liquid used for suspension) once or twice a day during 14 days
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	ACI-3024
Primary outcome measure	Safety/tolerability measured using Adverse events (AEs), physical and neurological examinations, vital signs measurements, 12 lead electrocardiogram parameters, incidence of laboratory abnormalities, and MRI in multiple ascending dose cohorts over 37 days (SAD part) or 70 Days (MAD part)
Secondary outcome measures	Pharmacokinetics (PK) measured using levels of ACI-3024 in plasma, urine, and cerebrospinal fluid (CSF) by liquid chromatography over 7 days (SAD part) or 28 Days (MAD part)
Overall study start date	04/02/2019
Completion date	24/08/2020

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	80
Total final enrolment	80
Key inclusion criteria	1. Aged 20 to 59 years inclusive (non-elderly participants), or 60 to 80 years inclusive (elderly participants) Non-Japanese participants: 1. Body mass index between 18.0 and 30.0 kg/m² 2. Body weight between 50 and 100 kg (males) or between 45 and 80 kg (females) Japanese participants: 1. First-generation Japanese subjects (biological parents and all biological grandparents are of exclusively Japanese descent and were born in Japan) 2. Body mass index between 17.0 and 30.0 kg/m² 3. Body weight between 45 and 100 kg (males) or between 40 and 80 kg (females)
Key exclusion criteria	1. History of, or current: liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, psychiatric or metabolic disturbances; any inflammatory illness; or any other illness that the investigator considers should exclude the subject and which may interfere with the study assessments 2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator MAD cohorts only: 1. Lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months according to the Columbia Suicide Severity Rating Scale (C-SSRS) at screening 2. Screening brain MRI scan that shows evidence of significant abnormality that would suggest a clinically significant finding that may impact the subject’s ability to safely participate in the study, in the opinion of the investigator 3. History of alcoholism or drug/chemical abuse within 2 years prior to screening. 4. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check in 5. History of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV at screening 6. History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus) positive, or positive hepatitis panel at screening 7. Positive pregnancy test result at screening or check in 8. Clinically significant impaired hepatic function at screening or check in , defined as either of the following (confirmed by repeat): 8.1. Serum ALT or AST >1.25 × upper limit of normal 8.2. Total bilirubin >1.5 × upper limit of normal 9. Serum albumin or total plasma protein outside of the clinical reference range for the testing laboratory at screening or check in 10. Creatinine clearance <60 ml/min as assessed by the Cockcroft-Gault equation Participants undergoing MRI (MAD part): 1. Have any contraindications for MRI studies, including claustrophobia, or the presence of metal (ferromagnetic) implants, or a cardiac pacemaker
Date of first enrolment	20/06/2019
Date of final enrolment	04/03/2020

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Covance Clinical Research Unit Ltd

Springfield House
Hyde Street
Leeds
LS2 9LH
United Kingdom

Sponsor information

AC Immune (Switzerland)
Industry

EPFL Innocation Park
Building B
Lausanne
1015
Switzerland

Phone	+41 21 345 91 21
Email	info@acimmune.com
Website	https://www.acimmune.com/
"ROR"	https://ror.org/00e8cky09

Funders

Funder type

Industry

AC Immune

No information available

Results and Publications

Intention to publish date	01/01/1900
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	This is a phase 1 study in healthy volunteers with no publication intended.
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available as the study is an early phase study and results are not planned to be disseminated.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			26/07/2023	No	No

Editorial Notes

01/04/2021: Internal review.
16/03/2021: Trial’s existence confirmed by London - Brent Research Ethics Committee.