A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease

NCT00818662 | Completed Phase 3 Results DMC

• 1 other identifier: 160701
• Study Type: interventional
• Target: 390
• Locations: 2 countries
• Sites: 41

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).

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)

  The ADAS-Cog is a validated psychometric instrument that evaluates memory (word recall, word recognition), attention, reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). This test was administered by experienced raters certified by Alzheimer's Disease Cooperative Study (ADCS) at each site. Scores on the ADAS-Cog range from 0-70 with higher scores indicating greater impairment; hence increases from baseline reflect potential cognitive deterioration.

  Baseline & 18 months

• Change From Baseline at 18 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

  The ADCS-ADL scale is a validated tool to assess instrumental and basic activities of daily living based on a 23 item structured interview of the caregiver or qualified study partner. Scores on the ADCS-ADL range from 0-78 with lower scores indicating greater impairment; hence decreases from baseline reflect potential functional deterioration.

  Baseline & 18 Months

Secondary Outcomes (25)

• Change From Baseline at 9 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)

  Baseline & 9 months

• Change From Baseline at 9 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

  Baseline & 9 Months

• Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment

  Baseline & 9 Months

• Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment

  Baseline & 18 Months

• Change From Baseline at 18 Months in the Modified Mini-Mental State Examination (3MS) Examination

  Baseline & 18 months

Study Arms (4)

IGIV, 10% 400mg/kg

EXPERIMENTAL

Immune Globulin Intravenous (Human), 10% (IGIV, 10%)

Biological: Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg

IGIV, 10% 200mg/kg

EXPERIMENTAL

Immune Globulin Intravenous (Human), 10% (IGIV, 10%)

Biological: Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg

Human Albumin 0.25% Solution - 4 mL/kg

PLACEBO COMPARATOR

0.25% human albumin solution infused at 4 mL/kg/2weeks

Biological: Placebo solution: Human Albumin 0.25% - 4 mL/kg

Human Albumin 0.25% Solution - 2 mL/kg

PLACEBO COMPARATOR

0.25% human albumin solution infused at 2 mL/kg/2weeks

Biological: Placebo solution: Human Albumin 0.25% - 2 mL/kg

Interventions

Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg BIOLOGICAL

400 mg/kg bodyweight every 2 weeks for 70 weeks

Also known as: Gammagard Liquid, KIOVIG

IGIV, 10% 400mg/kg

Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg BIOLOGICAL

200 mg/kg bodyweight every 2 weeks for 70 weeks

Also known as: Gammagard Liquid

IGIV, 10% 200mg/kg

Placebo solution: Human Albumin 0.25% - 4 mL/kg BIOLOGICAL

Placebo solution: 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks

Human Albumin 0.25% Solution - 4 mL/kg

Placebo solution: Human Albumin 0.25% - 2 mL/kg BIOLOGICAL

Placebo solution: 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks

Human Albumin 0.25% Solution - 2 mL/kg

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Any other forms of dementia
• Medical issues that might increase the risk of treatment with IGIV, 10%, such as:
• Significant problems with blood pressure, heart disease, clotting disorders, strokes or recent heart attacks
• Evidence of current bleeding in the brain by MRI
• Serious problems with the liver or kidneys
• Allergies to blood products
• Medical issues that might interfere with the evaluation of the treatment of dementia or might make dementia worse, such as:
• Diabetes
• Recent treatment with chemotherapy or immune suppression
• The recent use of other investigational drugs, especially antibody therapy for AD
• Severe headaches or psychiatric problems

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Alzheimer's Disease Cooperative Study (ADCS): collaborator

Study Sites (41)

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Sun City, Arizona, United States

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Tucson, Arizona, United States

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Irvine, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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National City, California, United States

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Orange, California, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Miami Beach, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Lexington, Kentucky, United States

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Burlington, Massachusetts, United States

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Paw Paw, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Liverpool, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Cleveland, Ohio, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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North Charleston, South Carolina, United States

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Franklin, Tennessee, United States

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Dallas, Texas, United States

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Salt Lake City, Utah, United States

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Madison, Wisconsin, United States

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Vancouver, British Columbia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Related Publications (3)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 28381506 DERIVED

MeSH Terms

Conditions

Dementia; Alzheimer Disease

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2009
• First Posted: January 8, 2009
• Study Start: December 19, 2008
• Primary Completion: December 10, 2012
• Study Completion: December 10, 2012
• Last Updated: May 19, 2021
• Results First Posted: October 28, 2014

Record last verified: 2021-04

Locations

US (37); CA (4)