CERE-110 in Subjects With Mild to Moderate Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by:
Ceregene
ClinicalTrials.gov Identifier:
NCT00087789
First received: July 13, 2004
Last updated: June 30, 2010
Last verified: June 2010
  Purpose

This is a Phase I clinical study to assess the safety, tolerability and biologic activity of in vivo AAV-mediated delivery of CERE-110. Up to 12 subjects will receive open label CERE-110 in dose-escalating fashion. All subjects will receive bilateral, stereotactic injections of CERE-110 for a total of four (Dose A and B) and six (Dose C) injections to target the basal forebrain region of the brain containing the nucleus basalis of Meynert (NBM). All study participants will be observed for a 24-month period and then followed annually.


Condition Intervention Phase
Alzheimer's Disease
Genetic: CERE-110: Adeno-Associated Virus Delivery of NGF
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Dose-Escalating Study to Assess the Safety and Tolerability of CERE-110 [Adeno-Associated Virus (AAV)-Based Vector-Mediated Delivery of Beta-Nerve Growth Factor (NGF)] in Subjects With Mild to Moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Ceregene:

Primary Outcome Measures:
  • Safety and tolerability of three different doses of CERE-110 in subjects with mild to moderate Alzheimer's disease [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: June 2004
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: CERE-110: Adeno-Associated Virus Delivery of NGF
    CERE-110 2.0 x 10^10 vg, CERE-110 1.0 x 10^11 vg, CERE-110 2.0 x 10^11 vg
  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Alzheimer's disease as determined by NINCDS/ADRDA criteria.
  • Score of ≤ 4 on a modified Hachinski Ischemia Scale
  • Mini-Mental State Exam (MMSE) score in the range of 16 to 28, inclusive
  • No significant neurological or medical abnormalities contraindicating surgery, MRI/PET imaging or study participation
  • Subjects stable on standard-of-care medications (i.e., acetylcholinesterase inhibitors) for Alzheimer's disease for 3 months prior to entry
  • A Hamilton Depression Scale score of ≤ 12 on a 17-item scale and no history of major depressive episode within the last 2 years
  • A score of < 15 on the Beck Depression Inventory
  • Adequate visual and auditory acuity to allow neuropsychological testing
  • Good health with no clinically significant medical or psychological conditions
  • An MRI of the head at screen that is negative for evidence of infection, tumor, infarction or other focal (e.g., subdural hematoma) or generalized lesions(e.g., v hydrocephalus) and without clinical symptoms suggestive of intervening neurological disease
  • Normal serum B12, thyroid function tests, and negative syphilis antibody test
  • The informed consent document must be signed by both:

a competent and willing subject, and a surrogate identified by the participant, or a legally authorized power of attorney for Health Care, or a family member

Exclusion Criteria:

  • History of cancer within the last five years, except superficial basal or squamous cell skin cancer or cervical carcinoma in situ
  • History of alcohol abuse or dependence within the last two years
  • Liver serum transaminases (AST and/or ALT) > 5 times the upper limit of normal; total and/or direct bilirubin > 1.5 mg/dL, hemoglobin < 9mg/dL; PT and PTT > 2 times the upper limit of normal; creatinine clearance < 30 mL/min; positive serology for HBV or HCV; absolute neutrophil count < 1,500 cells/mm3 and a platelet count < 100,000/mm3
  • Any significant systemic illness, unstable or severe medical condition(s) that could put the subject at risk during the study, interfere with outcome measures or affect compliance with the protocol procedures
  • Centrally active beta-blockers, anti-Parkinsonian medications, psychostimulants, antipsychotics, neuroleptics, or narcotic analgesics, long-acting benzodiazepines or barbiturates, hypertensive agents with a CNS effect, short-acting anxiolytics or sedative hypnotics more frequently than two times per week within 14 days of screening, herbal products for Alzheimer's disease, antidepressants with significant cholinergic side effects (e.g., tricyclics), initiation or change in dose of standard treatment for Alzheimer's disease
  • Other medication with significant cholinergic or anticholinergic side effects
  • Warfarin (coumadin), nonsteroidal anti-inflammatory drugs, aspirin, Prozac, or Ginkgo biloba within 14 days of surgery
  • Subjects who have received investigational agents or been exposed to investigational devices for 30 days prior to enrollment
  • Subjects with a history of receiving gene transfer products of any kind
  • Subjects who cannot undergo MRI or PET screening
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087789

Locations
United States, California
University of California San Diego
San Diego, California, United States, 92037
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Ceregene
Investigators
Study Director: Joao Siffert, M.D. Ceregene
  More Information

No publications provided

Responsible Party: Joao Siffert, MD, Chief Medical Officer, Ceregene, Inc.
ClinicalTrials.gov Identifier: NCT00087789     History of Changes
Other Study ID Numbers: CERE-110-01
Study First Received: July 13, 2004
Last Updated: June 30, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Ceregene:
Alzheimer's Disease
Gene Transfer

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 23, 2014