Phase 3 IGIV, 10% in Alzheimer´s Disease

NCT01524887 | Terminated Phase 3 Results DMC

• 2 other identifiers: 1610032011-000914-21
• Study Type: interventional
• Target: 508
• Locations: 8 countries
• Sites: 69

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.

Conditions

Alzheimer´s Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline to 9 Months (actual time frame)

• 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.

  Baseline to 9 Months (actual time frame)

Secondary Outcomes (11)

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

  Baseline to 9 Months (actual time frame)

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

  Baseline to 9 Months (actual time frame)

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

  Baseline to 9 Months (actual time frame)

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

  Baseline to 9 Months (actual time frame)

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

  Baseline to 9 Months (actual time frame)

Study Arms (3)

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

EXPERIMENTAL

Biological: Immune Globulin Intravenous (Human), 10% Solution

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

EXPERIMENTAL

Biological: Immune Globulin Intravenous (Human), 10% Solution

Placebo control

PLACEBO COMPARATOR

Biological: Human albumin 0.25%

Interventions

Immune Globulin Intravenous (Human), 10% Solution BIOLOGICAL

Intravenous infusion every 2 weeks over 18 months

Also known as: IGIV, 10%

IGIV, 10% at high dose (0.4 g/kg); IGIV, 10% at low dose (0.2 g/kg)

Human albumin 0.25% BIOLOGICAL

Intravenous infusion every 2 weeks over 18 months

Placebo control

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (69)

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Long Beach, California, United States

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San Diego, California, United States

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Santa Ana, California, United States

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Boca Raton, Florida, United States

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Delray Beach, Florida, United States

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Edgewater, Florida, United States

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Orlando, Florida, United States

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Decatur, Georgia, United States

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Chicago, Illinois, United States

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Springfield, Illinois, United States

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Paducah, Kentucky, United States

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Saint Paul, Minnesota, United States

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Olive Branch, Mississippi, United States

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Las Vegas, Nevada, United States

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Berlin, New Jersey, United States

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Chester, New Jersey, United States

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Eatontown, New Jersey, United States

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Summit, New Jersey, United States

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Toms River, New Jersey, United States

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Albany, New York, United States

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Brooklyn, New York, United States

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Latham, New York, United States

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Manhasset, New York, United States

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New Hyde Park, New York, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Providence, Rhode Island, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Bennington, Vermont, United States

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Charlottesville, Virginia, United States

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Milwaukee, Wisconsin, United States

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Woodville South, South Australia, Australia

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Edegem, Belgium

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Ghent, Belgium

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Hasselt, Belgium

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Leuven, Belgium

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Roeselare, Belgium

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Akashi, Japan

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Akita, Japan

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Azumino, Japan

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Chiba, Japan

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Fukui, Japan

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Kyoto, Japan

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Niigata, Japan

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Osaka, Japan

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Saga, Japan

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Tokushima, Japan

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Tokyo, Japan

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Lublin, Poland

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Ścinawa, Poland

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Warsaw, Poland

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Barakaldo, Vizcaya, Spain

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Barcelona, Spain

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Madrid, Spain

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Valencia, Spain

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Uckfield, East Sussex, United Kingdom

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Bath, United Kingdom

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Brentford, United Kingdom

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Brighton, United Kingdom

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Glasgow, United Kingdom

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MeSH Terms

Interventions

gamma-Globulins; Solutions

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The primary and secondary outcome measures were originally planned to be assessed at 18 months. However, as the study was terminated early, an analysis was completed at 9 months instead, in a subset of subjects who had received 9 months of treatment.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 20, 2012
• First Posted: February 2, 2012
• Study Start: January 23, 2012
• Primary Completion: July 16, 2013
• Study Completion: July 16, 2013
• Last Updated: May 19, 2021
• Results First Posted: March 31, 2015

Record last verified: 2021-04

Locations

GB (5); BE (5); PL (3); CA (3); US (37); JP (11); ES (4); AU (1)