A Study of ACI-24 in Adults With Down Syndrome

NCT04373616 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: ACI-24-DS-19022020-000634-18
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a prospective multicenter, placebo-controlled, double-blind, randomized study to assess the effect of one dose ACI-24 versus placebo over a 74-week treatment period and 26-week safety follow-up period.

Conditions

Down Syndrome

Keywords

Alzheimer related disease; Cognitive decline

Outcome Measures

Primary Outcomes (6)

• Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related).

  from screening up to week 100

• Mean change from baseline in systolic and diastolic blood pressure (mmHg)

  from baseline up to week 100

• Mean change from baseline in heart rate (bpm)

  from baseline up to week 100

• Mean change from baseline in body temperature (degree Celsius)

  from baseline up to week 100

• Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS)

  from baseline up to week 100

• Number of participants with abnormal MRI results

  Occurrence of Amyloid-related imaging abnormalities (ARIA)

  from baseline up to week 100

Secondary Outcomes (8)

• Change from baseline of composite standardized uptake value ratio (SUVR) assessed by amyloid PET imaging using florbetaben

  from baseline up to week 76

• Change from baseline in anti-Aβ antibody titers in blood

  from baseline up to week 100

• Change from baseline of amyloid-related biomarkers (Aβ1-40, Aβ1-42), total tau, phosphorylated tau and NfL in blood/CSF (in pg/ml) (CSF is optional)

  from baseline up to week 100

• Change from baseline of brain tau load assessed by tau PET imaging

  from screening up to week 74

• Change from baseline of cognitive performance using Cambridge Neuropsychological Test Automated Battery - Paired Associates Learning [CANTAB-PAL]

  from baseline up to week 100

Study Arms (2)

ACI-24

EXPERIMENTAL

Biological: ACI-24

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

ACI-24 BIOLOGICAL

injections

ACI-24

Placebo BIOLOGICAL

injections

Placebo

Eligibility Criteria

• Age: 40 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21.
• Age ≥ 40 and ≤ 50 years at screening.
• Elevated brain Aβ as evidenced by composite SUVR ≥ 1.25 on florbetaben PET scan assessed by central reading.
• Subjects, their legal representatives (if applicable) and/or their study partners in the opinion of the investigator, are able to understand and to provide written informed consent before starting any study-related activities.
• In the opinion of the investigator, subjects, their legal representatives (if applicable) and/or their study partners are able to fully participate in the study, be sufficiently proficient in the official languages(s) of the country they are living in, and be capable of reliably completing study assessments.
• Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.
• Subjects must have a study partner who has direct and regular contact with the subject and who is able to provide reliable answers to questions related to the subject, according to the study investigator.
• Subjects in preclinical stage of AD or with mild cognitive impairment due to AD.

You may not qualify if:

• Clinical diagnosis of AD dementia in DS as per International Classification of Diseases 10 (ICD-10).
• DSQIID \> 20.
• Intelligence quotient score ≤ 40 (KBIT-2).
• Diagnosis of autism spectrum disorder or any other unstable/uncontrolled psychiatric or neurologic illness other than DS.
• Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study vaccine (eg, severe and untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke or other cerebrovascular conditions), as per investigator's judgement.
• Subjects considered to be unable to complete any study exams and assessments (eg, because of significant hearing or visual impairments or other disabilities), according to the investigator, and potentially affecting study compliance.
• DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years.
• History or presence of uncontrolled seizures. If history of seizures, they must be well controlled with no occurrence of seizures in the 2 years before study screening. The use of antiepileptic medications is permitted.
• History of meningitis or meningoencephalitis.
• History of moderate or severe traumatic brain injury.
• History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in-situ, in-situ prostate cancer, or in-situ breast cancer which have been fully removed and are considered cured.
• History of inflammatory neurological disorders.
• History of autoimmune disease with potential for central nervous system involvement.
• Severe infections or a major surgical operation within 3 months before screening.
• History of chronic or recurrent infections judged to be clinically significant by the investigator and would potentially hamper the evaluation of efficacy and safety assessments.

Sponsors & Collaborators

• AC Immune SA: lead

MeSH Terms

Conditions

Down Syndrome; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Michael S. Rafii, MD, PhD

  Alzheimer's Therapeutic Research Institute USC Keck School of Medicine of the University of Southern California, San Diego, CA, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: May 4, 2020
• Study Start: October 1, 2021
• Primary Completion: April 1, 2024
• Study Completion: October 1, 2024
• Last Updated: October 22, 2021

Record last verified: 2021-10