TerminatedPhase 3Results posted

Phase 3 IGIV, 10% in Alzheimer´s Disease

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

Lead sponsor

Baxalta now part of Shire

Asset

Immunoglobulin

Listed sites

Recruiting sites

Enrollment

508

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MRI contraindications excluded•Brain MRI excludes superficial siderosis, vasogenic edema

Primary endpoints

•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID161003

Eudract number2011-000914-21

NCT IDNCT01524887

Timeline

Milestones

Study start2012-01-23actual

Study first posted2012-02-02estimated

Primary completion2013-07-16actual

Study completion2013-07-16actual

Results first posted2015-03-31estimated

Last update posted2021-05-19actual

Assets

Drug assets

Immunoglobulin

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age89 Years

SexAll

Healthy volunteersNot accepted

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

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)

Endpoints (26)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Caregiver / quality of life

Safety / tolerability / PK

Global cognition

Function / daily living

Behavior / neuropsychiatric

Neuroimaging

Global cognition

2 endpoints

Primary/protocol endpoint

Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog)

Time frame:Baseline to 9 Months (actual time frame)

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog)

Time frame:Baseline to 9 Months (actual time frame)

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=21 Participants	4.0	6.44
IGIV, 10% at Low Dose (0.2 g/kg)n=28 Participants	4.4	8.56
Placebo Controln=36 Participants	3.1	4.28

Difference in least square means1.495% CI-1.0 - 3.9p0.243Mixed Models Analysis

Difference in least square means1.095% CI-1.2 - 3.3p0.370Mixed Models Analysis

Function / daily living

2 endpoints

Primary/protocol endpoint

Change From Baseline to Month 18 in Alzheimer´s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) Inventory

Time frame:Baseline to 9 Months (actual time frame)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/registry result

Change From Baseline to Month 18 in Alzheimer´s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) Inventory

Time frame:Baseline to 9 Months (actual time frame)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=21 Participants	-8.1	7.36
IGIV, 10% at Low Dose (0.2 g/kg)n=29 Participants	-5.0	11.64
Placebo Controln=36 Participants	-3.8	9.26

Difference in least square means-3.995% CI-7.4 - -0.3p0.033Mixed Models Analysis

Difference in least square means-0.995% CI-4.2 - 2.4p0.586Mixed Models Analysis

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change From Baseline to Month 18 in Neuropsychiatric Inventory (NPI)

Time frame:Baseline to 9 Months (actual time frame)

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Month 18 in Neuropsychiatric Inventory (NPI)

Time frame:Baseline to 9 Months (actual time frame)

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=21 Participants	2.3	5.76
IGIV, 10% at Low Dose (0.2 g/kg)n=29 Participants	3.8	12.44
Placebo Controln=36 Participants	0.6	5.68

Difference in least square means1.195% CI-2.6 - 4.7p0.571Mixed Models Analysis

Difference in least square means3.795% CI0.3 - 7.1p0.032Mixed Models Analysis

Neuroimaging

2 endpoints

Secondary/protocol endpoint

Change From Baseline to Month 18 in Volumetric Magnetic Resonance Imaging (MRI) Parameters: Rate of Whole Brain Atrophy and Ventricular Enlargement

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Month 18 in Volumetric Magnetic Resonance Imaging (MRI) Parameters: Rate of Whole Brain Atrophy and Ventricular Enlargement

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Posted result

Group	Value (mean), mm^3	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=9 Participants	0.00065	0.00059
IGIV, 10% at Low Dose (0.2 g/kg)n=15 Participants	0.00057	0.00070
Placebo Controln=17 Participants	0.00067	0.00163

Difference in least square means-0.0002695% CI-0.00126 - 0.00073p0.593ANCOVA

Difference in least square means0.0000395% CI-0.00080 - 0.00086p0.940ANCOVA

Caregiver / quality of life

6 endpoints

Secondary/protocol endpoint

ADCS-Clinical Global Impression of Change (CGIC) at 18 Months

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Month 18 in Logsdon Quality of Life in Alzheimer´s Disease (QOL-AD)

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Month 18 in Impact of Alzheimer´s Disease on Caregiver Questionnaire (IADCQ)

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Secondary/registry result

ADCS-Clinical Global Impression of Change (CGIC) at 18 Months

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)n=10 Participants	4.3	-3.7 - 4.8
IGIV, 10% at Low Dose (0.2 g/kg)n=16 Participants	4.4	-4.0 - 4.9
Placebo Controln=16 Participants	4.5	-4.1 - 5.0

Difference in least square means-0.295% CI-1.0 - 0.5p0.501Mixed Models Analysis

Difference in least square means-0.195% CI-0.7 - 0.5p0.783Mixed Models Analysis

Secondary/registry result

Change From Baseline to Month 18 in Logsdon Quality of Life in Alzheimer´s Disease (QOL-AD)

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=16 Participants	-0.1	4.43
IGIV, 10% at Low Dose (0.2 g/kg)n=26 Participants	0.4	3.68
Placebo Controln=30 Participants	0.1	4.56

Difference in least square means-0.595% CI-2.8 - 1.7p0.633Mixed Models Analysis

Difference in least square means-0.095% CI-2.0 - 2.0p0.981Mixed Models Analysis

Secondary/registry result

Change From Baseline to Month 18 in Impact of Alzheimer´s Disease on Caregiver Questionnaire (IADCQ)

Time frame:Baseline to 9 Months (actual time frame)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
IGIV, 10% at High Dose (0.4 g/kg)n=19 Participants	5.8	4.13
IGIV, 10% at Low Dose (0.2 g/kg)n=27 Participants	1.9	6.66
Placebo Controln=30 Participants	1.4	5.97

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of Participants Experiencing Study Product-related Adverse Events (AEs) and/or Serious Adverse Events (SAEs)

Time frame:Throughout the study period: 18 Months

event count, event

Secondary/protocol endpoint

Number of Infusions Temporally Associated With AEs and/or SAEs

Time frame:During or within 72 hours of completion of an infusion

event count, event

Secondary/registry result

Number of Participants Experiencing Study Product-related Adverse Events (AEs) and/or Serious Adverse Events (SAEs)

Time frame:Throughout the study period: 18 Months

event count, event

Posted result

Group	Value (number), participants	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)Participants with product-related AEs (incl SAEs)n=83 Participants	31	-
Participants with product-related non-serious AEsn=83 Participants	30	-
Participants with product-related SAEsn=83 Participants	1	-
IGIV, 10% at Low Dose (0.2 g/kg)Participants with product-related AEs (incl SAEs)n=85 Participants	25	-
Participants with product-related non-serious AEsn=85 Participants	25	-
Participants with product-related SAEsn=85 Participants	0	-
Placebo ControlParticipants with product-related AEs (incl SAEs)n=83 Participants	16	-
Participants with product-related non-serious AEsn=83 Participants	16	-
Participants with product-related SAEsn=83 Participants	1	-

Secondary/registry result

Number of Infusions Temporally Associated With AEs and/or SAEs

Time frame:During or within 72 hours of completion of an infusion

event count, event

Posted result

Group	Value (number), infusions	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)n=83 Participants	72	-
IGIV, 10% at Low Dose (0.2 g/kg)n=85 Participants	80	-
Placebo Controln=83 Participants	47	-

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Number of Participants Experiencing Any AEs and/or SAEs

Time frame:Throughout the study period: 18 Months

event count, event

Secondary/protocol endpoint/low confidence

Number of Infusions Associated With AEs and/or SAEs Occurring During or Within 7 Days of Completion of an Infusion

Time frame:During or within 7 days of completion of an infusion

event count, event

Secondary/protocol endpoint/low confidence

Number of Infusions Causally Associated With AEs and/or SAEs

Time frame:Throughout the study period: 18 Months

event count, event

Secondary/protocol endpoint/low confidence

Number of Infusions Discontinued, Slowed, or Interrupted Due to an AE

Time frame:Throughout infusions, approximately 2-5 hours

event count, event

Secondary/registry result/low confidence

Number of Participants Experiencing Any AEs and/or SAEs

Time frame:Throughout the study period: 18 Months

event count, event

Posted result

Group	Value (number), participants	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)Participants with AEs (incl SAEs)n=83 Participants	57	-
Participants with non-serious AEsn=83 Participants	55	-
Participants with serious AEs (SAEs)n=83 Participants	5	-
IGIV, 10% at Low Dose (0.2 g/kg)Participants with AEs (incl SAEs)n=85 Participants	54	-
Participants with non-serious AEsn=85 Participants	53	-
Participants with serious AEs (SAEs)n=85 Participants	7	-
Placebo ControlParticipants with AEs (incl SAEs)n=83 Participants	49	-
Participants with non-serious AEsn=83 Participants	48	-
Participants with serious AEs (SAEs)n=83 Participants	7	-

Secondary/registry result/low confidence

Number of Infusions Associated With AEs and/or SAEs Occurring During or Within 7 Days of Completion of an Infusion

Time frame:During or within 7 days of completion of an infusion

event count, event

Posted result

Group	Value (number), infusions	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)n=83 Participants	97	-
IGIV, 10% at Low Dose (0.2 g/kg)n=85 Participants	107	-
Placebo Controln=83 Participants	72	-

Secondary/registry result/low confidence

Number of Infusions Causally Associated With AEs and/or SAEs

Time frame:Throughout the study period: 18 Months

event count, event

Posted result

Group	Value (number), infusions	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)n=83 Participants	46	-
IGIV, 10% at Low Dose (0.2 g/kg)n=85 Participants	48	-
Placebo Controln=83 Participants	30	-

Secondary/registry result/low confidence

Number of Infusions Discontinued, Slowed, or Interrupted Due to an AE

Time frame:Throughout infusions, approximately 2-5 hours

event count, event

Posted result

Group	Value (number), infusions	Reported bounds
IGIV, 10% at High Dose (0.4 g/kg)n=83 Participants	7	-
IGIV, 10% at Low Dose (0.2 g/kg)n=85 Participants	2	-
Placebo Controln=83 Participants	1	-

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.