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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01524887




Registration number
NCT01524887
Ethics application status
Date submitted
20/01/2012
Date registered
2/02/2012
Date last updated
19/05/2021

Titles & IDs
Public title
Phase 3 IGIV, 10% in Alzheimer´s Disease
Scientific title
A Phase 3 Randomized, Double-blind, Placebo-Controlled Study of the Safety and Effectiveness of Immune Globulin Intravenous (Human), 10% Solution (IGIV, 10%) for the Treatment of Mild to Moderate Alzheimer's Disease
Secondary ID [1] 0 0
2011-000914-21
Secondary ID [2] 0 0
161003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer´s Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Immune Globulin Intravenous (Human), 10% Solution
Treatment: Other - Human albumin 0.25%

Experimental: IGIV, 10% at high dose (0.4 g/kg) -

Experimental: IGIV, 10% at low dose (0.2 g/kg) -

Placebo comparator: Placebo control -


Treatment: Other: Immune Globulin Intravenous (Human), 10% Solution
Intravenous infusion every 2 weeks over 18 months

Treatment: Other: Human albumin 0.25%
Intravenous infusion every 2 weeks over 18 months
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog)
Timepoint [1] 0 0
Baseline to 9 Months (actual time frame)
Primary outcome [2] 0 0
Change From Baseline to Month 18 in Alzheimer´s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) Inventory
Timepoint [2] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [1] 0 0
ADCS-Clinical Global Impression of Change (CGIC) at 18 Months
Timepoint [1] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [2] 0 0
Change From Baseline to Month 18 in Neuropsychiatric Inventory (NPI)
Timepoint [2] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [3] 0 0
Change From Baseline to Month 18 in Volumetric Magnetic Resonance Imaging (MRI) Parameters: Rate of Whole Brain Atrophy and Ventricular Enlargement
Timepoint [3] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [4] 0 0
Change From Baseline to Month 18 in Logsdon Quality of Life in Alzheimer´s Disease (QOL-AD)
Timepoint [4] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [5] 0 0
Change From Baseline to Month 18 in Impact of Alzheimer´s Disease on Caregiver Questionnaire (IADCQ)
Timepoint [5] 0 0
Baseline to 9 Months (actual time frame)
Secondary outcome [6] 0 0
Number of Participants Experiencing Study Product-related Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
Timepoint [6] 0 0
Throughout the study period: 18 Months
Secondary outcome [7] 0 0
Number of Participants Experiencing Any AEs and/or SAEs
Timepoint [7] 0 0
Throughout the study period: 18 Months
Secondary outcome [8] 0 0
Number of Infusions Temporally Associated With AEs and/or SAEs
Timepoint [8] 0 0
During or within 72 hours of completion of an infusion
Secondary outcome [9] 0 0
Number of Infusions Associated With AEs and/or SAEs Occurring During or Within 7 Days of Completion of an Infusion
Timepoint [9] 0 0
During or within 7 days of completion of an infusion
Secondary outcome [10] 0 0
Number of Infusions Causally Associated With AEs and/or SAEs
Timepoint [10] 0 0
Throughout the study period: 18 Months
Secondary outcome [11] 0 0
Number of Infusions Discontinued, Slowed, or Interrupted Due to an AE
Timepoint [11] 0 0
Throughout infusions, approximately 2-5 hours

Eligibility
Key inclusion criteria
* Males or females of age 50 to 89 years inclusive at the time of screening
* Written informed consent obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures
* Written informed consent obtained from an able and competent caregiver who is willing to comply with the requirements of the protocol pertaining to him/her, including facilitating the subject's participation in the study
* Diagnosis of Probable Alzheimer´s Disease (AD) according to NINCDS-ADRDA* 1984 criteria (* National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association)
* Dementia of mild to moderate severity (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
* Willingness to comply with the requirements of the protocol and ability to comply with testing and infusion regimen, including adequate corrected visual acuity and hearing ability
* For at least 12 weeks prior to screening, on stable doses of AD medication(s) approved by local regulatory authorities. Subjects must not be on two acetylcholinesterase inhibitors concurrently.
* Venous access for repeated infusion and phlebotomy
* If receiving psychoactive medications (eg, 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
* For women of childbearing potential, the subject must have a negative pregnancy test at screening and must agree to employ adequate contraceptive measures (eg, birth control pills/patches, intrauterine device, or diaphragm or condom [for male partner] with spermicidal jelly or foam) throughout the course of the study
* For subjects with a coronary artery stent, the subject must receive documented medical clearance from an interventional cardiologist stating that the subject is not at increased risk for stent occlusion with immunoglobulin treatment
* For subjects with an endovascular stent, the subject must receive documented medical clearance from a vascular surgeon stating that the subject is not at increased risk for thromboembolic events with immunoglobulin treatment

Main
Minimum age
50 Years
Maximum age
89 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Possible AD by NINCDS-ADRDA criteria or non-Alzheimer dementia (eg, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, or dementia arising from other diseases or conditions such as Parkinson's disease, vitamin B12 deficiency, thyroid abnormalities)
* Current residence in a skilled nursing facility
* Contraindication to undergoing MRI (eg, pacemaker [with the exception of an MRI-compatible pacemaker], severe claustrophobia, ferromagnetic implants such as a metal plate)
* Clinically significant congestive heart failure (eg, New York Heart Association [NYHA] Class III/IV symptoms or untreated Class II)
* Current atrial fibrillation of unstable angina (angina at rest) or history of myocardial infarction within the 12 months prior to screening
* Uncontrolled hypertension defined as systolic blood pressure > 160 mm Hg and/or diastolic > 100 mm Hg confirmed upon repeated measures
* History of thrombosis and/or thromboembolic disease (central or peripheral) within the 12 months prior to screening
* Known history of procoagulant abnormalities (eg, factor V Leiden, antiphospholipid syndrome, protein S/protein C deficiency, AT III deficiency)
* History of intracerebral hemorrhage within the 5 years prior to screening
* Evidence on MRI of: greater than 4 microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis, vasogenic edema, a macrohemorrhage, major stroke, prominent white matter disease with a rating score of 3 on the age-related white matter changes (ARWMC) scale from the European Task Force on ARWMC, or multiple lacunae (defined as more than 2 lacunae that are greater than 0.5 mm in size)
* Head trauma with loss of consciousness, contusion, or open head injury within the 12 months prior to screening
* Uncontrolled seizure disorder as defined by two or more breakthrough seizures per year despite adequate antiepileptic drug (AED) treatment
* Modified Hachinski score > 4 at time of screening
* Subjects with active malignancy or history of malignancy within 5 years prior to screening with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment
* Active autoimmune or neuro-immunologic disorder
* Uncontrolled major depression, psychosis, or other major psychiatric disorder(s)
* Poorly controlled diabetes, defined as glycosylated (or glycated) hemoglobin (HbA1c) = 6.5% at screening
* Creatinine clearance < 50% of normal adjusted for age and gender, as calculated according to the Cockcroft-Gault formula, at the time of screening
* Known history of untreated vitamin B12 deficiency within 6 months prior to screening, or clinically significant abnormally low vitamin B12 at the time of screening
* Abnormal clinical chemistry panel or hematology panel meeting any one of the following criteria:
* Serum alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN)
* Clinically significant anemia that precludes repeated blood sampling or hemoglobin (Hgb) < 10.0 g/dL
* Absolute neutrophil count (ANC) < 1000 cells/µL
* Known coagulopathy or platelet counts < 100,000 cells/µL
* Total serum protein > 9 g/dL
* Known history of or positive serology at screening for one or more of the following: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) type 1/2 antibody
* Immunoglobulin A (IgA) deficiency (< 8 mg/dL)
* Known history of hypersensitivity following infusions of human blood or blood components (e.g. human immunoglobulins or human albumin)
* Currently receiving or has received: anti-CD20 therapy within 12 months prior to screening, or other immunomodulatory therapies (e.g. anti-TNF, anti-IL-1, interferon) within 12 weeks prior to screening. The following exceptions are allowed: non-systemic corticosteroids (eg, topical, opthalmic or inhaled glucocorticoids) and low-dose systemic corticosteroids (prednisone < 10 mg/day or its equivalent)
* Currently receiving or has received intravenous or subcutaneous immunoglobulin treatment within the 2 years prior to screening, or has received immunoglobulin in Baxter Protocol 160701
* Currently receiving or has received at any time active immunization aimed at modulating AD progression
* Currently receiving or has received within 12 months prior to screening any investigational device, drug or biologic (eg passive immunotherapies with monoclonal or polyclonal antibodies) aimed at modulating AD progression
* Subject has been exposed to an investigational product (IP) or investigational device within 12 weeks prior to screening or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
* Subject is a family member or employee of the investigator
* The subject is nursing or intends to begin nursing during the course of the study
* Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (eg, blood tests, urine tests, electrocardiogram, chest x-ray), that in medical judgment may impede the subject's participation in the study, pose increased risk to the subject, or confound the results of the study
* Currently receiving anti-coagulant agent and/or anti-platelet agent other than acetylsalicylic acid (a.k.a. aspirin)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/07/2013
Sample size
Target
Accrual to date
Final
508
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
- Woodville South
Recruitment postcode(s) [1] 0 0
- Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
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New York
Country [13] 0 0
United States of America
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Ohio
Country [14] 0 0
United States of America
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Oklahoma
Country [15] 0 0
United States of America
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Rhode Island
Country [16] 0 0
United States of America
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Texas
Country [17] 0 0
United States of America
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Vermont
Country [18] 0 0
United States of America
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Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Belgium
State/province [20] 0 0
Edegem
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Belgium
State/province [22] 0 0
Hasselt
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Roeselare
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Japan
State/province [27] 0 0
Akashi
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Japan
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Akita
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Japan
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Azumino
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Japan
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Chiba
Country [31] 0 0
Japan
State/province [31] 0 0
Fukui
Country [32] 0 0
Japan
State/province [32] 0 0
Kyoto
Country [33] 0 0
Japan
State/province [33] 0 0
Niigata
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Japan
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Osaka
Country [35] 0 0
Japan
State/province [35] 0 0
Saga
Country [36] 0 0
Japan
State/province [36] 0 0
Tokushima
Country [37] 0 0
Japan
State/province [37] 0 0
Tokyo
Country [38] 0 0
Poland
State/province [38] 0 0
Lublin
Country [39] 0 0
Poland
State/province [39] 0 0
Scinawa
Country [40] 0 0
Poland
State/province [40] 0 0
Warszawa
Country [41] 0 0
Spain
State/province [41] 0 0
Vizcaya
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
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Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Valencia
Country [45] 0 0
United Kingdom
State/province [45] 0 0
East Sussex
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Bath
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Brentford
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Brighton
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Baxalta now part of Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to provide evidence of efficacy and safety to support the development of IGIV, 10% as a treatment option for patients with mild to moderate Alzheimer´s Disease.
Trial website
https://clinicaltrials.gov/study/NCT01524887
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01524887