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

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ClinicalTrials.gov Identifier: NCT02738450
Recruitment Status : Recruiting
First Posted : April 14, 2016
Last Update Posted : July 4, 2019
Sponsor:
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

Tracking Information
First Submitted Date  ICMJE April 1, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date July 4, 2019
Actual Study Start Date  ICMJE March 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02738450 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
  • 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 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • 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 13 months in amyloid load assessed by PET [ Time Frame: through the study, an average of 13 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Immunogenicity of ACI-24 Vaccine in Adults With Down Syndrome
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Down Syndrome
Intervention  ICMJE
  • Biological: ACI-24 low dose
    ACI-24 administered as a sterile suspension in PBS via s.c. injection.
  • Biological: ACI-24 high dose
    ACI-24 administered as a sterile suspension in PBS via s.c. injection.
  • Biological: Placebo
    Placebo is a standard PBS sterile solution administrated via s.c. injection.
    Other Name: PBS
Study Arms  ICMJE
  • Active Comparator: ACI-24 low dose
    Vaccine formulation will be administrated s.c. 7 times.
    Intervention: Biological: ACI-24 low dose
  • Active Comparator: ACI-24 high dose
    Vaccine formulation will be administrated s.c. 7 times.
    Intervention: Biological: ACI-24 high dose
  • Placebo Comparator: Placebo
    The placebo is ready-to-use solution for injection, administrated s.c. 7 times.
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 11, 2016)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
  • 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.
  • History of chronic or recurrent infections judged to be clinically significant by the investigator.
  • History or presence of immunological or inflammatory conditions which are judged to be clinically significant by the investigator.
  • Celiac disease not on a gluten free diet for at least 3 months prior to study screening.
  • Chronic benign skin pathologies, unless viewed as clinically insignificant in the investigator's opinion.
  • 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.
  • In the opinion of the site investigator, deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, that are judged to be clinically significant.
  • 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 with an HbA1c of ≥ 8.0%.
  • 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 at stable dose, antipsychotics (typical or atypical), GABA agonists (e.g. gabapentin), or stimulants (e.g. methylphenidate, modafinil). In exceptional cases, low doses of atypical antipsychotics (e.g. risperidone up to 0.5 mg/day or quetiapine up to 50 mg/day) or benzodiazepines are only allowed after review by the site principal investigator, in consultation with the project director and/or medical monitors.
  • Current use of immunosuppressant or immunomodulating drugs or their use within the past 6 months prior to study screening. Current use of steroids or their use within the past 3 months prior to study screening.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julien Rongere +41(021) 345 9115 julien.rongere@acimmune.com
Contact: Genevieve Matthews +1(858) 246 1318 gfmatthews@ucsd.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02738450
Other Study ID Numbers  ICMJE ACI-24-1301
1R01AG047922-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party AC Immune SA
Study Sponsor  ICMJE AC Immune SA
Collaborators  ICMJE
  • National Institute on Aging (NIA)
  • Alzheimer's Disease Cooperative Study (ADCS)
  • LuMind Research Down Syndrome Foundation
Investigators  ICMJE
Study Chair: Olivier Sol AC Immune SA
Study Director: Michael S. Rafii, MD, PhD USC Keck School of Medicine of the University of Southern California, San Diego
PRS Account AC Immune SA
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP