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Alzheimer´s DiseasePhase 3NCT01524887

Phase 3 IGIV, 10% in Alzheimer´s Disease

A Phase 3 study testing Immune Globulin Intravenous (Human), 10% Solution and Human albumin 0.25% in people with Alzheimer´s Disease, run by Baxalta now part of Shire at 69 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. 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% Solution and Human albumin 0.25%
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
508 participants
Where
69 sitesin 8 countries
Study dates
23 Jan 2012to 16 Jul 2013
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

Who may be able to join

  • 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
Show all 51Show fewer
  • 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 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)

Who cannot join

None listed.

Trial locations and contacts

69 sites in 8 countries.

69 sites in 8 countries

United States37 sites

  • Study site

    Albany, New York

  • Study site

    Austin, Texas

  • Study site

    Bennington, Vermont

  • Study site

    Berlin, New Jersey

  • Study site

    Birmingham, Alabama

  • Study site

    Boca Raton, Florida

  • Study site

    Brooklyn, New York

  • Study site

    Charlottesville, Virginia

  • Study site

    Chester, New Jersey

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Decatur, Georgia

  • Study site

    Delray Beach, Florida

  • Study site

    Eatontown, New Jersey

  • Study site

    Edgewater, Florida

  • Study site

    Houston, Texas

  • Study site

    Las Vegas, Nevada

  • Study site

    Latham, New York

  • Study site

    Long Beach, California

  • Study site

    Manhasset, New York

  • Study site

    Milwaukee, Wisconsin

  • Study site

    New Hyde Park, New York

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Olive Branch, Mississippi

  • Study site

    Orlando, Florida

  • Study site

    Paducah, Kentucky

  • Study site

    Phoenix, Arizona

  • Study site

    Providence, Rhode Island

  • Study site

    Saint Paul, Minnesota

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    Santa Ana, California

  • Study site

    Springfield, Illinois

  • Study site

    Summit, New Jersey

  • Study site

    Toms River, New Jersey

  • Study site

    Tulsa, Oklahoma

Other trials in United States

Japan11 sites

  • Study site

    Akashi

  • Study site

    Akita

  • Study site

    Azumino

  • Study site

    Chiba

  • Study site

    Fukui

  • Study site

    Kyoto

  • Study site

    Niigata

  • Study site

    Osaka

  • Study site

    Saga

  • Study site

    Tokushima

  • Study site

    Tokyo

Other trials in Japan

Belgium5 sites

  • Study site

    Edegem

  • Study site

    Ghent

  • Study site

    Hasselt

  • Study site

    Leuven

  • Study site

    Roeselare

Other trials in Belgium

United Kingdom5 sites

  • Study site

    Bath

  • Study site

    Brentford

  • Study site

    Brighton

  • Study site

    Glasgow

  • Study site

    Uckfield, East Sussex

Other trials in United Kingdom

Spain4 sites

  • Study site

    Barakaldo, Vizcaya

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Valencia

Other trials in Spain

Canada3 sites

  • Study site

    Greenfield Park, Quebec

  • Study site

    Sherbrooke, Quebec

  • Study site

    Toronto, Ontario

Other trials in Canada

Poland3 sites

  • Study site

    Lublin

  • Study site

    Ścinawa

  • Study site

    Warsaw

Other trials in Poland

Australia1 site

  • Study site

    Woodville South, South Australia

Other trials in Australia

About this study

Official 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

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.

Being tested
Immune Globulin Intravenous (Human), 10% Solution, Human albumin 0.25%

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Immune Globulin Intravenous (Human), 10% SolutionBiological

    Also called IGIV, 10%

    Intravenous infusion every 2 weeks over 18 months

  • Human albumin 0.25%Biological

    Intravenous infusion every 2 weeks over 18 months

Study groups in NCT01524887
Study groupRoleWhat they receive
IGIV, 10% at high dose (0.4 g/kg)ExperimentalNot described
Receives: Biological: Immune Globulin Intravenous (Human), 10% Solution
IGIV, 10% at low dose (0.2 g/kg)ExperimentalNot described
Receives: Biological: Immune Globulin Intravenous (Human), 10% Solution
Placebo controlPlacebo comparatorNot described
Receives: Biological: Human albumin 0.25%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (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 to 9 Months (actual time frame)

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

    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 to 9 Months (actual time frame)

Secondary outcomes (11)

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

    The ADCS-CGIC is a validated categorical measure of change in a participant's global clinical status between baseline and follow-up visits, based on interview of the participant and the caregiver by a skilled and experienced clinician who was blinded to treatment assignment. The ADCS-CGIC score is based on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening).

    Measured: Baseline to 9 Months (actual time frame)

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

    The NPI is a validated instrument used to assess behavioral psychopathology in AD; it evaluates the frequency and severity of 10 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 to 9 Months (actual time frame)

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

    Measured: Baseline to 9 Months (actual time frame)

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

    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, with lower scores associated with a lower quality of life.

    Measured: Baseline to 9 Months (actual time frame)

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

    The IADCQ is a 12-item validated questionnaire that has been developed to measure the emotional, physical, and social impact of care giving on AD caregivers. Higher scores on the IADCQ are associated with a higher impact. IADCQ total score range: 0 (no impact) - 48 (greatest impact). Each item can be scored either 0 (Not at all), 1 (A little), 2 (Somewhat), 3 (A lot), or 4 (Extremely). As this is a 12-item scale, the minimum possible score is 0 and the maximum possible score is 4x12 = 48.

    Measured: Baseline to 9 Months (actual time frame)

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

    Measured: Throughout the study period: 18 Months

  7. Number of Participants Experiencing Any AEs and/or SAEs

    Measured: Throughout the study period: 18 Months

  8. Number of Infusions Temporally Associated With AEs and/or SAEs

    A temporal association was defined as an AE and/or SAE occurring during or within 72 hours of completion of an infusion, regardless of causality.

    Measured: During or within 72 hours of completion of an infusion

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

    Measured: During or within 7 days of completion of an infusion

  10. Number of Infusions Causally Associated With AEs and/or SAEs

    Measured: Throughout the study period: 18 Months

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

    Measured: Throughout infusions, approximately 2-5 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2012 (estimated)
  2. Study start23 Jan 2012
  3. Primary completion16 Jul 2013
  4. Study completion16 Jul 2013

Why it stopped: The study was terminated because the first Phase 3 did not demonstrate efficacy on the co-primary endpoints. The known safety profile remained unchanged.

Resources

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
508 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01524887
Sponsor's protocol ID
161003
Other IDs
2011-000914-21
Status last verified
Apr 2021
First submitted
20 Jan 2012
Last updated
19 May 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Immune Globulin Intravenous (Human), 10% Solution and Human albumin 0.25% in people with Alzheimer´s Disease, run by Baxalta now part of Shire at 69 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 0 exclusion criteria. 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: stopped early, 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 69 sites in United States, Japan, Belgium, United Kingdom, Spain and 3 more countries. 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 31 Mar 2015). 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 to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog) (time frame: Baseline to 9 Months (actual time frame)). 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 NCT01524887.

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; AzTrials last refreshed its copy on 6 Nov 2026.

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