Safety, Tolerability and Immunogenicity of ACI-24 Vaccine in Adults With Down Syndrome

NCT02738450 | Completed Phase 1 Results DMC

• 2 other identifiers: ACI-24-13011R01AG047922-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to test in adults with Down Syndrome the safety, tolerability and immunogenicity of a vaccine, ACI-24.

Conditions

Down Syndrome

Keywords

cognitive decline

Outcome Measures

Primary Outcomes (1)

• Antibody Titer (Serum Anti-Aβ1-42 Free IgG) - Mean Absolute Value

  All subjects who received at least 1 dose of the study treatment of either ACI-24 300 μg, ACI-24 1000 μg or placebo are considered. The measure is expressed in Arbitrary Units per mL (AU/mL). AU/mL in a sample is obtained by back-calculation towards the standard curve.

  Values at baseline (week 0) and week 50 are reported

Secondary Outcomes (9)

• Amyloid Beta 1-40 in Blood - Mean Absolute Value

  Values at baseline (week 0) and week 50 are reported

• CANTAB - MOT Latency Score

  Values at baseline (week 0) and week 50 are reported

• CANTAB - PAL First Attempt Memory Score

  Values at baseline (week 0) and week 50 are reported

• Brief Praxis Test (BPT) - Total Score

  Values at baseline (week 0) and week 50 are reported

• Vineland II - Communication Domain Standard Score

  Values at baseline (week 0) and week 50 are reported

Study Arms (3)

ACI-24 low dose

ACTIVE COMPARATOR

Vaccine formulation will be administrated s.c. 7 times.

Biological: ACI-24 low dose

ACI-24 high dose

ACTIVE COMPARATOR

Vaccine formulation will be administrated s.c. 7 times.

Biological: ACI-24 high dose

Placebo

PLACEBO COMPARATOR

The placebo is ready-to-use solution for injection, administrated s.c. 7 times.

Biological: Placebo

Interventions

ACI-24 low dose BIOLOGICAL

ACI-24 administered as a sterile suspension in PBS via s.c. injection.

ACI-24 low dose

ACI-24 high dose BIOLOGICAL

ACI-24 administered as a sterile suspension in PBS via s.c. injection.

ACI-24 high dose

Placebo BIOLOGICAL

Placebo is a standard PBS sterile solution administrated via s.c. injection.

Also known as: PBS

Placebo

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females with Down Syndrome aged ≥25 to ≤45 years, with a cytogenetic diagnosis being either Trisomy 21 or Complete Unbalanced Translocation of the Chromosome 21.
• Subjects and their study partner/legal representative in the opinion of the investigator able to understand and to provide written informed consent.
• Written informed consent obtained from subjects and their study partner/legal representative before any trial-related activities.
• In the opinion of the investigator able to fully participate in the trial and sufficiently proficient in English to be capable of reliably completing study assessments.
• Subjects have a study partner/legal representative who have direct contact with the subjects at least 10 hours per week and who can be asked questions about the subjects.

You may not qualify if:

• Subjects weighing less than 40 kg.
• IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
• In the investigators opinion, any clinically significant current psychiatric or neurologic illness, including a past illness with a risk of recurrence, other than Down syndrome.
• Any medical condition likely to significantly hamper the evaluation of safety of the study drug.
• DSM-IV criteria for drug or alcohol abuse or dependence currently met within the past five years.
• History or presence of uncontrolled seizures. If history of seizures, they must be well controlled with no occurrence of seizures in the past 2 years prior to study screening. The use of anti-epileptic medications is permitted.
• History of meningitis or meningoencephalitis.
• History of malignant neoplasms within 3 years prior to study screening or where there is current evidence of recurrent or metastatic disease.
• History of persistent cognitive deficits immediately following head trauma.
• History of inflammatory neurology disorders.
• History of autoimmune disease with potential for CNS involvement.
• MRI scan at screening showing a single area of cerebral vasogenic edema, superficial siderosis, or evidence of a prior macrohemorrhage, or showing more than four cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite").
• MRI examination cannot be done for any reason, including metal implants contraindicated for MRI studies and/or severe claustrophobia.
• Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures.
• Severe infections or a major surgical operation within 3 months prior to screening.

Sponsors & Collaborators

• AC Immune SA: lead
• National Institute on Aging (NIA): collaborator
• Alzheimer's Disease Cooperative Study (ADCS): collaborator
• LuMind IDSC Foundation: collaborator

Study Sites (4)

St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics

Phoenix, Arizona, 85013, United States

Location

UCSD Adult Down Syndrome Program

La Jolla, California, 92037-1712, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Rafii MS, Sol O, Mobley WC, Delpretti S, Skotko BG, Burke AD, Sabbagh MN, Yuan SH, Rissman RA, Pulsifer M, Evans C, Evans AC, Beth G, Fournier N, Gray JA, Dos Santos AM, Hliva V, Vukicevic M, Kosco-Vilbois M, Streffer J, Pfeifer A, Feldman HH. Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial. JAMA Neurol. 2022 Jun 1;79(6):565-574. doi: 10.1001/jamaneurol.2022.0983.

  PMID: 35532913 DERIVED

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

Limitations and Caveats

The study included a limited number of subjects, and, as a consequence, was not powered on cognition and clinical efficacy outcomes.

Results Point of Contact

• Title: Olivier Sol
• Organization: AC Immune

clinicaltrials@acimmune.com

+41 21 345 91 21

Study Officials

• Michael S. Rafii, MD, PhD

  USC Keck School of Medicine of the University of Southern California, San Diego

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: April 14, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: October 15, 2021
• Results First Posted: September 21, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Access Criteria: These clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research and will be provided after review and approval of their research proposal, their Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). Data sharing shall be in accordance with ADCS' data sharing plan in its grant application and applicable NIH policy in effect at the time of the NIH award.

Locations

US (4)