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Safety, Tolerability and Immunogenicity of ACI-24 Vaccine in Adults With Down Syndrome (3 Star)

This study is currently recruiting participants.
Verified May 2017 by AC Immune SA
Sponsor:
ClinicalTrials.gov Identifier:
NCT02738450
First Posted: April 14, 2016
Last Update Posted: May 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Institute on Aging (NIA)
Alzheimer's Disease Cooperative Study (ADCS)
LuMind Research Down Syndrome Foundation
Information provided by (Responsible Party):
AC Immune SA
  Purpose
The purpose of this study is to test in adults with Down Syndrome the safety, tolerability and immunogenicity of a vaccine, ACI-24.

Condition Intervention Phase
Down Syndrome Biological: ACI-24 low dose Biological: ACI-24 high dose Biological: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ib Multi-Center, Double-Blind, Randomized, Placebo-Controlled Dose Escalation Study of the Safety, Tolerability and Immunogenicity of ACI-24 in Adults With Down Syndrome

Resource links provided by NLM:


Further study details as provided by AC Immune SA:

Primary Outcome Measures:
  • Percentage of patients with treatment emergent adverse events and serious adverse events [ Time Frame: through study completion, an average of 25 months ]
  • Antibody titer (serum anti-Aβ Ig) [ Time Frame: through study completion, an average of 25 months ]

Secondary Outcome Measures:
  • Change from baseline over 25 months on CANTAB battery [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months on RBANS [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months on Vineland [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months on NPI scale [ Time Frame: through study completion, an average of 25 months ]
  • Global Impression of Change over 25 months [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months in plasma/CSF amyloid [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months in plasma/CSF tau [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline in whole brain and hippocampal volume measured by MRI [ Time Frame: through study completion, an average of 25 months ]
  • Incidence of ARIA on MRI scans over 25 months [ Time Frame: through study completion, an average of 25 months ]
  • Change from baseline over 25 months in Brief Praxis Test (BPT) [ Time Frame: through study completion, an average of 25 months ]

Estimated Enrollment: 24
Study Start Date: March 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ACI-24 low dose
Vaccine formulation will be administrated s.c. 7 times.
Biological: ACI-24 low dose
ACI-24 administered as a sterile suspension in PBS via s.c. injection.
Active Comparator: ACI-24 high dose
Vaccine formulation will be administrated s.c. 7 times.
Biological: ACI-24 high dose
ACI-24 administered as a sterile suspension in PBS via s.c. injection.
Placebo Comparator: Placebo
The placebo is ready-to-use solution for injection, administrated s.c. 7 times.
Biological: Placebo
Placebo is a standard PBS sterile solution administrated via s.c. injection.
Other Name: PBS

Detailed Description:

This is a prospective multi-center, placebo controlled, double-blind and randomized dose escalation study of 2 doses of ACI-24 versus Placebo over 24 months with a total of 21 visits.

All subjects will receive the study medication (ACI-24 or Placebo) 7 times via s.c. injection (12 months) and will be followed up for 12 months after the last dose with a final safety and efficacy assessment.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   25 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Subjects weighing less than 40 kg.
  • IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
  • Any current psychiatric or neurologic diagnosis other than Down Syndrome. (History of minor (but not major) depression according to DSM-IV criteria is permitted, but must be on stable treatment for 3 months prior to screening.)
  • 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 seizure disorder or encephalitis. (History of seizures that are well controlled (no seizures in past 3 years) on anti-epileptic medications is permitted).
  • History of malignant neoplasms within 3 years prior to study entry 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 including meningoencephalitis.
  • 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.
  • History of chronic or recurrent infections or immunological or inflammatory conditions which could hamper interpretation of safety. (Celiac disease on a gluten free diet for at least 3 months prior to baseline will be allowed).
  • Any vaccine received within the past 2 months before baseline, except influenza vaccine which if indicated must be given at least 2 weeks prior to baseline.
  • Clinically significant arrhythmias or other abnormalities on ECG at screening. (Minor abnormalities documented as clinically insignificant by the investigator will be allowed.)
  • Clinically significant abnormal vital signs including sustained sitting blood pressure greater than 160/90 mmHg.
  • Clinically significant abnormal hematology and biochemistry values including, but not limited to, elevations greater than 1.5 times the upper limit of normal value of AST, ALT, or creatinine.
  • Subjects with treated hypothyroidism not on a stable dose of medication for at least 3 months prior to screening and having clinically significant abnormal serum T-4 and TSH at screening.
  • Subjects with diabetes mellitus controlled by diet, oral medication or insulin with an HbA1c of ≥ 8.0% and random serum glucose value of > 170 mg/dl.
  • Subjects who have been receiving any experimental drug for Down Syndrome with a washout less than 30 days or less than five halflives of the drug, whichever is longer.
  • Female subjects being pregnant as confirmed by serum testing at screening or planning to be pregnant or lactating.
  • Female subjects not using a reliable method of contraception (unless abstaining).
  • Patient receiving any anticoagulant drug, or aspirin at doses greater than 100 mg daily in the 7 days prior to lumbar puncture (in order to avoid risk of bleeding during scheduled or unscheduled lumbar puncture)
  • Use of antidepressants other than SSRI/SNRIs, antipsychotics (typical or atypical), GABA agonists (e.g. gabapentin), stimulants (e.g. methylphenidate, modafinil), oral steroids, immunosuppressant or immunomodulating drugs, regular use of Benzodiazepines (e.g. lorazepam).
  • Use of Cholinesterase Inhibitor or use of Glutamatergic drugs (Topiramate, Memantine, Lamotrigine) if not on stable dose for at least 3 months prior to screening.
  • Subjects who have donated blood or blood products during the 30 days prior to screening who plan to donate blood while participating in the study or within four weeks after completion of the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02738450


Contacts
Contact: Gautam Maitra +41(021) 345 9115 gautam.maitra@acimmune.com
Contact: Genevieve Matthews +1(858) 246 1318 gfmatthews@ucsd.edu

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics Recruiting
Phoenix, Arizona, United States, 85013
Contact: Sandy Quintanilla    602-406-7054    Sandy.Quintanilla@DignityHealth.org   
Principal Investigator: Marwan N. Sabbagh, MD, FAAN, CCRI         
United States, California
UCSD Adult Down Syndrome Program Recruiting
La Jolla, California, United States, 92037-1712
Contact: Asmaa Al-hamdani, M.B.Ch.B, MAS    +1(858) 249 2526    aalhamda@ucsd.edu   
Contact: Holly Bowron Hainley, MSN, MA,NP-C    +1(858) 249 2527    hbhainley@ucsd.edu   
Principal Investigator: William Mobley, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Amy Torres, BS    617-726-7927    aetorres@partners.org   
Principal Investigator: Brian Skotko, MD, MPP         
Sponsors and Collaborators
AC Immune SA
National Institute on Aging (NIA)
Alzheimer's Disease Cooperative Study (ADCS)
LuMind Research Down Syndrome Foundation
Investigators
Study Chair: Wolfgang Barth AC Immune SA
Study Director: Michael S. Rafii, MD, PhD University of California, San Diego
  More Information

Responsible Party: AC Immune SA
ClinicalTrials.gov Identifier: NCT02738450     History of Changes
Other Study ID Numbers: ACI-24-1301
1R01AG047922-01 ( U.S. NIH Grant/Contract )
First Submitted: April 1, 2016
First Posted: April 14, 2016
Last Update Posted: May 10, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by AC Immune SA:
cognitive decline

Additional relevant MeSH terms:
Syndrome
Down Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Vaccines
Immunologic Factors
Physiological Effects of Drugs