Alzheimer´s DiseasePhase 3NCT00818662
A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease
A Phase 3 study testing Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg and Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg in people with Alzheimer´s Disease, run by Baxalta now part of Shire at 41 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 89 years
- Conditions the study is for
- Alzheimer´s Disease
- What is being tested?
- Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg and Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 390 participants
- Where
- 41 sitesin 2 countries
- Study dates
- 19 Dec 2008to 10 Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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:
- 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
Trial locations and contacts
41 sites in 2 countries.
41 sites in 2 countries
United States37 sites
Study site
Birmingham, Alabama
Study site
Burlington, Massachusetts
Study site
Chicago, Illinois
Study site
Cleveland, Ohio
Study site
Dallas, Texas
Study site
Franklin, Tennessee
Study site
Iowa City, Iowa
Study site
Irvine, California
Study site
Kansas City, Kansas
Study site
La Jolla, California
Study site
Las Vegas, Nevada
Study site
Lexington, Kentucky
Study site
Liverpool, New York
Study site
Los Angeles, California
Study site
Madison, Wisconsin
Study site
Miami Beach, Florida
Study site
National City, California
Study site
New Haven, Connecticut
Study site
New York, New York
Study site
North Charleston, South Carolina
Study site
Omaha, Nebraska
Study site
Orange, California
Study site
Paw Paw, Michigan
Study site
Philadelphia, Pennsylvania
Study site
Phoenix, Arizona
Study site
Portland, Oregon
Study site
Providence, Rhode Island
Study site
Rochester, Minnesota
Study site
Rochester, New York
Study site
Salt Lake City, Utah
Study site
Sarasota, Florida
Study site
St Louis, Missouri
Study site
Sun City, Arizona
Study site
Tampa, Florida
Study site
Tucson, Arizona
Study site
Tulsa, Oklahoma
Study site
Washington D.C., District of Columbia
Canada4 sites
Study site
London, Ontario
Study site
Montreal, Quebec
Study site
Toronto, Ontario
Study site
Vancouver, British Columbia
About this study
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
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).
Read the 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.
- Conditions
- Alzheimer´s Disease
- Being tested
- Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg, Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg, Placebo solution: Human Albumin 0.25% - 4 mL/kg, Placebo solution: Human Albumin 0.25% - 2 mL/kg
- Keywords
- Alzheimer´s, Dementia, Dementia of Alzheimer Type, Immunoglobulins, Gammaglobulins, Immune Globulin Intravenous (IGIV), Intravenous Immune Globulin (IVIG), Antibodies, Amyloid, Immunotherapy
- Medical subject headings
- Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kgBiological
Also called Gammagard Liquid, KIOVIG
400 mg/kg bodyweight every 2 weeks for 70 weeks
Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kgBiological
Also called Gammagard Liquid
200 mg/kg bodyweight every 2 weeks for 70 weeks
Placebo solution: Human Albumin 0.25% - 4 mL/kgBiological
Placebo solution: 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks
Placebo solution: Human Albumin 0.25% - 2 mL/kgBiological
Placebo solution: 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks
| Study group | Role | What they receive |
|---|---|---|
| IGIV, 10% 400mg/kg | Experimental | Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Receives: Biological: Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg |
| IGIV, 10% 200mg/kg | Experimental | Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Receives: 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 Receives: 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 Receives: Biological: Placebo solution: Human Albumin 0.25% - 2 mL/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline & 18 Months
Secondary outcomes (25)
Change From Baseline at 9 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.
Measured: Baseline & 9 months
Change From Baseline at 9 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.
Measured: Baseline & 9 Months
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
The ADCS-CGIC is a validated categorical measure of change in a participant's clinical condition between baseline and follow-up visits; it is used to assess global clinical status. The ADCS CGIC score is based on direct examination of the participant and an interview of the caregiver. The rater should refer to the baseline ADCS-CGIC worksheets in making a rating. A skilled and experienced clinician who is blinded to treatment assignment rates the participant on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). 1= Very much better 2= Much better 3= A little better 4= Same 5= A little worse 6= Much worse 7= Very much worse
Measured: Baseline & 9 Months
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
The ADCS-CGIC is a validated categorical measure of change in a participant's clinical condition between baseline and follow-up visits; it is used to assess global clinical status. The ADCS CGIC score is based on direct examination of the participant and an interview of the caregiver. The rater should refer to the baseline ADCS-CGIC worksheets in making a rating. A skilled and experienced clinician who is blinded to treatment assignment rates the participant on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). 1= Very much better 2= Much better 3= A little better 4= Same 5= A little worse 6= Much worse 7= Very much worse
Measured: Baseline & 18 Months
Change From Baseline at 18 Months in the Modified Mini-Mental State Examination (3MS) Examination
The 3MS is a comprehensive validated instrument that provides a 100 point composite rating for spatial and temporal orientation, verbal recall, simple attention, working memory, naming, repetition, comprehension, writing and constructional abilities. Scores range from 0 to 100 with lower values indicating greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Neuropsychiatric Inventory (NPI) Assessment
The NPI is a validated instrument used to assess behavioral psychopathology in AD; it evaluates the frequency and severity of 12 neuropsychiatric features including delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, aberrant motor activity, sleep and night-time behavior change, and appetite and eating change. The NPI total score ranged 0-144, with higher scores indicating greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Participant Response
The QOL AD is a validated, 13-item instrument developed specifically for individuals with dementia. The assessment rates the participant's quality of life for physical, emotional, interpersonal, and environmental domains. The QOL-AD total score ranged 13-52. Lower scores on the QOL AD are associated with a lower quality of life.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Caregiver Response
The QOL AD is a validated, 13-item instrument developed specifically for individuals with dementia. The assessment rates the participant's quality of life for physical, emotional, interpersonal, and environmental domains. The QOL-AD total score ranged 13-52. Lower scores on the QOL AD are associated with a lower quality of life.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Forward
This test assesses working memory and attention, the rater asks the participant to repeat single-digit number sequences of increasing length, which are read aloud by the rater (in forward or backward order). Two trials are presented for each sequence length, and the test is ended when the participant misses both trials at a given sequence length. The WAIS-R score ranged from 0-14. Results are presented as total number correct; therefore, lower numbers represent greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Backward
This test assesses working memory and attention, the rater asks the participant to repeat single-digit number sequences of increasing length, which are read aloud by the rater (in forward or backward order). Two trials are presented for each sequence length, and the test is ended when the participant misses both trials at a given sequence length. The WAIS-R score ranged from 0-14. Results are presented as total number correct; therefore, lower numbers represent greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: FAS Verbal Fluency
In the FAS assessment of phenomic verbal fluency, participants are given 1 minute each to name as many words as they can that begin with a specified letter (F, A, S). To receive credit, words must be verifiable in a dictionary, cannot be proper nouns, and cannot be the same word or variations of the same word (e.g., the same word with a different ending, such as 'acts,' 'acted,' 'acting'). Results are presented as total number correct; therefore, lower numbers indicate greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Symbol Substitution
WAIS-R digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Animals Category Fluency
In this test, which assesses semantic verbal fluency, participants are given 1 minute to name as many items in the category "animals" as possible. To receive credit that word cannot be a mythical animal, but can be an animal species; breed; male, female, or infant name for a species (e.g., bull, cow, calf); in addition, names for birds, fish, reptiles, and insects receive credit. Results are presented as total number correct; therefore, lower numbers indicate greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part A
This test, which has 2 parts, is used to assess processing speed, visuomotor and perceptual scanning skills, and executive function. In Part A, 25 circles each containing a number between 1 and 25 are randomly placed on a sheet of paper, and the participant is asked to draw a line as quickly as possible between each circle in ascending numerical order. In Part B, 25 circles are again randomly placed on a sheet of paper; however, in this test 13 of the circles contain the numbers 1 through 13, and the remaining 12 circles contain the letters A through L. In this test, the participant must draw a line as quickly as possible between the circles in alternating between numbers and letters in ascending order (e.g., 1 to A, A to 2, 2 to B,…). Total values for TMT Part A range between 0 and 150 seconds. Results are presented as time to complete; therefore, higher numbers indicate greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part B
This test, which has 2 parts, is used to assess processing speed, visuomotor and perceptual scanning skills, and executive function. In Part A, 25 circles each containing a number between 1 and 25 are randomly placed on a sheet of paper, and the participant is asked to draw a line as quickly as possible between each circle in ascending numerical order. In Part B, 25 circles are again randomly placed on a sheet of paper; however, in this test 13 of the circles contain the numbers 1 through 13, and the remaining 12 circles contain the letters A through L. In this test, the participant must draw a line as quickly as possible between the circles in alternating between numbers and letters in ascending order (e.g., 1 to A, A to 2, 2 to B,…). Total values for TMT Part B range between 0 and 300 seconds. Results are presented as time to complete; therefore, higher numbers indicate greater impairment.
Measured: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Clock Drawing Test
In this test, which assesses constructional ability, visuoperception, and executive functioning, the participant is given a blank sheet of paper and asked to draw the face of a clock showing the numbers and 2 hands set to 'ten after eleven.' Results are presented as score obtained (range 0 to 5, with 0 indicating the greatest impairment).
Measured: Baseline & 18 months
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class
Measured: Throughout the study period, approximately 4 years
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class
Measured: Throughout the study period, approximately 4 years
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class
Related and unrelated non-SAEs
Measured: Throughout the study period, approximately 4 years
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class
Related and unrelated SAEs
Measured: Throughout the study period, approximately 4 years
Number of Infusions Temporally Associated With Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
Refers to non-SAEs and/or SAEs occurring during infusion or within 72 hours of completion of infusion (regardless of causality)
Measured: During or within 72 hours of completion of an infusion
Number of Infusions With Causally Associated Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
Each adverse event (AE) that was considered related to investigational product (IP) was linked to the most recent infusion administered
Measured: Throughout the study period, approximately 4 years
Number of Infusions Discontinued, Slowed, or Interrupted Due to an Adverse Event (AE)
Measured: Throughout each infusion period
Number of Participants Experiencing a Clinically Significant Decrease in Hemoglobin (>1.5 g/dL) Between Consecutive Visits
Measured: Throughout the study period, approximately 4 years
Number of Participants Experiencing a Clinically Significant Rash
Participants requiring systemic therapy or discontinuation from further treatment
Measured: Throughout the study period, approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2009 (estimated)
- Study start19 Dec 2008
- Primary completion10 Dec 2012
- Study completion10 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer´s DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 390 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Disease Cooperative Study (ADCS)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00818662
- Sponsor's protocol ID
- 160701
- Status last verified
- Apr 2021
- First submitted
- 7 Jan 2009
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
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.
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.
PubMed 28381506
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00818662
- Acronym / sponsor ID
- 160701
- Conditions
- Alzheimer´s Disease
- Keywords
- Alzheimer´s, Dementia, Dementia of Alzheimer Type, Immunoglobulins, Gammaglobulins, Immune Globulin Intravenous (IGIV), Intravenous Immune Globulin (IVIG), Antibodies
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 390 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Disease Cooperative Study (ADCS)
- Study start
- 19 Dec 2008 (actual)
- Primary completion
- 10 Dec 2012 (actual)
- Study completion
- 10 Dec 2012 (actual)
- First posted
- 8 Jan 2009 (estimated)
- Results
- Posted 28 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IGIV, 10% 400mg/kg | Experimental | Biological: Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kgImmune Globulin Intravenous (Human), 10% (IGIV, 10%) |
| IGIV, 10% 200mg/kg | Experimental | Biological: Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kgImmune Globulin Intravenous (Human), 10% (IGIV, 10%) |
| Human Albumin 0.25% Solution - 4 mL/kg | Placebo comparator | Biological: Placebo solution: Human Albumin 0.25% - 4 mL/kg0.25% human albumin solution infused at 4 mL/kg/2weeks |
| Human Albumin 0.25% Solution - 2 mL/kg | Placebo comparator | Biological: Placebo solution: Human Albumin 0.25% - 2 mL/kg0.25% human albumin solution infused at 2 mL/kg/2weeks |
Who may qualify
- Ages
- 50 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kgAlso: Gammagard Liquid, KIOVIG400 mg/kg bodyweight every 2 weeks for 70 weeks | Biological | IGIV, 10% 400mg/kg |
| Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kgAlso: Gammagard Liquid200 mg/kg bodyweight every 2 weeks for 70 weeks | Biological | IGIV, 10% 200mg/kg |
| Placebo solution: Human Albumin 0.25% - 4 mL/kgPlacebo solution: 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks | Biological | Human Albumin 0.25% Solution - 4 mL/kg |
| Placebo solution: Human Albumin 0.25% - 2 mL/kgPlacebo solution: 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks | Biological | Human Albumin 0.25% Solution - 2 mL/kg |
Primary outcome
Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)
Time frame: Baseline & 18 months
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.
Change From Baseline at 18 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time frame: Baseline & 18 Months
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.
25 secondary outcomes
Change From Baseline at 9 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)
Time frame: Baseline & 9 months
Change From Baseline at 9 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time frame: Baseline & 9 Months
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
Time frame: Baseline & 9 Months
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment
Time frame: Baseline & 18 Months
Change From Baseline at 18 Months in the Modified Mini-Mental State Examination (3MS) Examination
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Neuropsychiatric Inventory (NPI) Assessment
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Participant Response
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Caregiver Response
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Forward
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Backward
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: FAS Verbal Fluency
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Symbol Substitution
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Animals Category Fluency
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part A
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part B
Time frame: Baseline & 18 months
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Clock Drawing Test
Time frame: Baseline & 18 months
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class
Time frame: Throughout the study period, approximately 4 years
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class
Time frame: Throughout the study period, approximately 4 years
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class
Time frame: Throughout the study period, approximately 4 years
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class
Time frame: Throughout the study period, approximately 4 years
Number of Infusions Temporally Associated With Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
Time frame: During or within 72 hours of completion of an infusion
Number of Infusions With Causally Associated Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)
Time frame: Throughout the study period, approximately 4 years
Number of Infusions Discontinued, Slowed, or Interrupted Due to an Adverse Event (AE)
Time frame: Throughout each infusion period
Number of Participants Experiencing a Clinically Significant Decrease in Hemoglobin (>1.5 g/dL) Between Consecutive Visits
Time frame: Throughout the study period, approximately 4 years
Number of Participants Experiencing a Clinically Significant Rash
Time frame: Throughout the study period, approximately 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundRelkin 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.
- BackgroundNgo 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.
- Derived from this study: PubMed 28381506Relkin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
41 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg and Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg in people with Alzheimer´s Disease, run by Baxalta now part of Shire at 41 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog) (time frame: Baseline & 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00818662, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.