Phase 3 IGIV, 10% in Alzheimer´s Disease
2021년 4월 30일 업데이트: Baxalta now part of Shire
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.
연구 개요
상태
종료됨
정황
연구 유형
중재적
등록 (실제)
508
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Alabama
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Birmingham, Alabama, 미국
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Arizona
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Phoenix, Arizona, 미국
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California
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Long Beach, California, 미국
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San Diego, California, 미국
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Santa Ana, California, 미국
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Florida
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Boca Raton, Florida, 미국
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Delray Beach, Florida, 미국
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Edgewater, Florida, 미국
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Orlando, Florida, 미국
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Georgia
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Decatur, Georgia, 미국
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Illinois
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Chicago, Illinois, 미국
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Springfield, Illinois, 미국
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Kentucky
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Paducah, Kentucky, 미국
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Minnesota
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Saint Paul, Minnesota, 미국
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Mississippi
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Olive Branch, Mississippi, 미국
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Nevada
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Las Vegas, Nevada, 미국
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New Jersey
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Berlin, New Jersey, 미국
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Chester, New Jersey, 미국
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Eatontown, New Jersey, 미국
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Summit, New Jersey, 미국
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Toms River, New Jersey, 미국
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New York
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Albany, New York, 미국
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Brooklyn, New York, 미국
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Latham, New York, 미국
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Manhasset, New York, 미국
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New Hyde Park, New York, 미국
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Ohio
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Cincinnati, Ohio, 미국
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Oklahoma
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Oklahoma City, Oklahoma, 미국
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Tulsa, Oklahoma, 미국
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Rhode Island
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Providence, Rhode Island, 미국
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Texas
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Austin, Texas, 미국
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Dallas, Texas, 미국
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Houston, Texas, 미국
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San Antonio, Texas, 미국
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Vermont
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Bennington, Vermont, 미국
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Virginia
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Charlottesville, Virginia, 미국
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Wisconsin
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Milwaukee, Wisconsin, 미국
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Edegem, 벨기에
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Gent, 벨기에
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Hasselt, 벨기에
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Leuven, 벨기에
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Roeselare, 벨기에
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Barcelona, 스페인
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Madrid, 스페인
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Valencia, 스페인
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Vizcaya
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Barakaldo, Vizcaya, 스페인
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Bath, 영국
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Brentford, 영국
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Brighton, 영국
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Glasgow, 영국
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East Sussex
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Uckfield, East Sussex, 영국
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Akashi, 일본
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Akita, 일본
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Azumino, 일본
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Chiba, 일본
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Fukui, 일본
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Kyoto, 일본
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Niigata, 일본
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Osaka, 일본
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Saga, 일본
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Tokushima, 일본
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Tokyo, 일본
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Ontario
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Toronto, Ontario, 캐나다
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Quebec
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Greenfield Park, Quebec, 캐나다
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Sherbrooke, Quebec, 캐나다
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Lublin, 폴란드
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Scinawa, 폴란드
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Warszawa, 폴란드
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South Australia
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Woodville South, South Australia, 호주
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
50년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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 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)
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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위약 비교기: 위약 대조군
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Intravenous infusion every 2 weeks over 18 months
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실험적: IGIV, 10% at high dose (0.4 g/kg)
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Intravenous infusion every 2 weeks over 18 months
다른 이름들:
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실험적: IGIV, 10% at low dose (0.2 g/kg)
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Intravenous infusion every 2 weeks over 18 months
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog)
기간: Baseline to 9 Months (actual time frame)
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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.
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Baseline to 9 Months (actual time frame)
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Change From Baseline to Month 18 in Alzheimer´s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) Inventory
기간: Baseline to 9 Months (actual time frame)
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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.
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Baseline to 9 Months (actual time frame)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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ADCS-Clinical Global Impression of Change (CGIC) at 18 Months
기간: Baseline to 9 Months (actual time frame)
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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).
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Baseline to 9 Months (actual time frame)
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Change From Baseline to Month 18 in Neuropsychiatric Inventory (NPI)
기간: Baseline to 9 Months (actual time frame)
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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.
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Baseline to 9 Months (actual time frame)
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Change From Baseline to Month 18 in Volumetric Magnetic Resonance Imaging (MRI) Parameters: Rate of Whole Brain Atrophy and Ventricular Enlargement
기간: Baseline to 9 Months (actual time frame)
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Baseline to 9 Months (actual time frame)
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Change From Baseline to Month 18 in Logsdon Quality of Life in Alzheimer´s Disease (QOL-AD)
기간: Baseline to 9 Months (actual time frame)
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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.
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Baseline to 9 Months (actual time frame)
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Change From Baseline to Month 18 in Impact of Alzheimer´s Disease on Caregiver Questionnaire (IADCQ)
기간: Baseline to 9 Months (actual time frame)
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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.
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Baseline to 9 Months (actual time frame)
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Number of Participants Experiencing Study Product-related Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
기간: Throughout the study period: 18 Months
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Throughout the study period: 18 Months
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Number of Participants Experiencing Any AEs and/or SAEs
기간: Throughout the study period: 18 Months
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Throughout the study period: 18 Months
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Number of Infusions Temporally Associated With AEs and/or SAEs
기간: During or within 72 hours of completion of an infusion
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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.
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During or within 72 hours of completion of an infusion
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Number of Infusions Associated With AEs and/or SAEs Occurring During or Within 7 Days of Completion of an Infusion
기간: During or within 7 days of completion of an infusion
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During or within 7 days of completion of an infusion
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Number of Infusions Causally Associated With AEs and/or SAEs
기간: Throughout the study period: 18 Months
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Throughout the study period: 18 Months
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Number of Infusions Discontinued, Slowed, or Interrupted Due to an AE
기간: Throughout infusions, approximately 2-5 hours
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Throughout infusions, approximately 2-5 hours
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2012년 1월 23일
기본 완료 (실제)
2013년 7월 16일
연구 완료 (실제)
2013년 7월 16일
연구 등록 날짜
최초 제출
2012년 1월 20일
QC 기준을 충족하는 최초 제출
2012년 1월 31일
처음 게시됨 (추정)
2012년 2월 2일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2021년 5월 19일
QC 기준을 충족하는 마지막 업데이트 제출
2021년 4월 30일
마지막으로 확인됨
2021년 4월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .