Clinical trial NCT00818662: A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease
Official title: A Randomized, Double-Blind, Placebo-Controlled, Two Dose Arm, Parallel Study of the Safety and Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer´s Disease
Keywords: Alzheimer´s
Dementia
Dementia of Alzheimer Type
Immunoglobulins
Gammaglobulins
Immune Globulin Intravenous (IGIV)
Intravenous Immune Globulin (IVIG)
Antibodies
Amyloid
Immunotherapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Alzheimer's Disease Cooperative Study (ADCS)
First posted: 2009-01-08
Enrollment: 390
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy and safety of 2 doses of Immune Globulin Intravenous (IGIV), 10% administered every 2 weeks as an intravenous (IV) infusion compared with placebo in participants with mild to moderate Alzheimer's disease (AD).

Detailed description: Study visits: Each participant will be tested at the investigational site, and if qualified, will be treated intravenously (through a vein) every two weeks for 70 weeks (approximately 18 months). The first three infusions must be done at the site, but if the infusions are well tolerated, subsequent infusions may be done by a qualified healthcare provider in the home or other suitable location. Each participant must return to the site every 3 months for evaluation of cognition as well as blood tests and scans of the brain.

Eligibility criteria: Main Inclusion Criteria:

* Written informed consent - participant (or participant´s legally acceptable representative) and caregiver who are willing and able to participate for the duration of the study
* Diagnosis of probable Alzheimer´s Disease (AD)
* Dementia of mild to moderate severity defined as mini-mental state examination (MMSE) 16-26 inclusive at the time of screening
* Neuroimaging (computed tomography \[CT\] or MRI) performed after symptom onset consistent with AD diagnosis
* Ability to comply with testing and infusion regimen, including fluency in English or Spanish, adequate corrected visual acuity and hearing ability
* On stable doses of regulatory authority approved AD medication(s) for at least 3 months prior to screening. These medications must be continued throughout this study.
* If receiving psychoactive medications (e.g. antidepressants other than monoamine oxidase inhibitors (MAOIs) and most tricyclics, antipsychotics, anxiolytics, anticonvulsants, mood stabilizers, etc), must be on stable doses for at least 6 weeks prior to screening

Main Exclusion Criteria (Reasons why it might not be appropriate to participate):

* Any other forms of dementia
* Medical issues that might increase the risk of treatment with IGIV, 10%, such as:

  1. Significant problems with blood pressure, heart disease, clotting disorders, strokes or recent heart attacks
  2. Evidence of current bleeding in the brain by MRI
  3. Serious problems with the liver or kidneys
  4. Allergies to blood products
* Medical issues that might interfere with the evaluation of the treatment of dementia or might make dementia worse, such as:

  1. Diabetes
  2. Recent treatment with chemotherapy or immune suppression
  3. The recent use of other investigational drugs, especially antibody therapy for AD
  4. Severe headaches or psychiatric problems

Primary outcomes:
measure: Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline & 18 Months
Secondary outcomes:
measure: Change From Baseline at 9 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)
timeFrame: Baseline & 9 months
measure: Change From Baseline at 9 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline & 9 Months
measure: Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
timeFrame: Baseline & 9 Months
measure: Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
timeFrame: Baseline & 18 Months
measure: Change From Baseline at 18 Months in the Modified Mini-Mental State Examination (3MS) Examination
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Neuropsychiatric Inventory (NPI) Assessment
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Participant Response
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Caregiver Response
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Forward
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Backward
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: FAS Verbal Fluency
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Symbol Substitution
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Animals Category Fluency
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part A
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part B
timeFrame: Baseline & 18 months
measure: Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Clock Drawing Test
timeFrame: Baseline & 18 months
measure: Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Infusions Temporally Associated With Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
timeFrame: During or within 72 hours of completion of an infusion
measure: Number of Infusions With Causally Associated Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Infusions Discontinued, Slowed, or Interrupted Due to an Adverse Event (AE)
timeFrame: Throughout each infusion period
measure: Number of Participants Experiencing a Clinically Significant Decrease in Hemoglobin (>1.5 g/dL) Between Consecutive Visits
timeFrame: Throughout the study period, approximately 4 years
measure: Number of Participants Experiencing a Clinically Significant Rash
timeFrame: Throughout the study period, approximately 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Sun City
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Irvine
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: National City
country: United States
state: California
city: Orange
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Miami Beach
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Burlington
country: United States
state: Massachusetts
city: Paw Paw
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Liverpool
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: North Charleston
country: United States
state: South Carolina
city: Franklin
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Madison
country: United States
state: Wisconsin
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Relkin N, Gessert D, Stokes K, Adamiak B, Ngo LY, Thomas R, Gelmont D, Aisen P. The Gammaglobulin Alzheimer Partnership Study (GAP): Design, screening, enrollment and futility analysis results. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8[4 Suppl], P456. 2012.
citation: Ngo L, Adamiak B, Gelmont D. A confirmatory phase 3 randomized, double-blind, placebo-controlled study of the safety and effectiveness of immune globulin intravenous (human), 10% solution (Gammagard Liquid/Kiovig) for the treatment of mild to moderate Alzheimer's Disease. Poster Presentation: Alzheimer's Association International Conference on Alzheimer's Disease (ICAD), Paris, France July 16-21 2011.
citation: Relkin NR, Thomas RG, Rissman RA, Brewer JB, Rafii MS, van Dyck CH, Jack CR, Sano M, Knopman DS, Raman R, Szabo P, Gelmont DM, Fritsch S, Aisen PS; Alzheimer's Disease Cooperative Study. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology. 2017 May 2;88(18):1768-1775. doi: 10.1212/WNL.0000000000003904. Epub 2017 Apr 5.