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Phase 3 IGIV, 10% in Alzheimer´s Disease

30 de abril de 2021 atualizado por: 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.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

508

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Austrália
    • South Australia
      • Woodville South, South Australia, Austrália
  • Bélgica
      • Edegem, Bélgica
      • Gent, Bélgica
      • Hasselt, Bélgica
      • Leuven, Bélgica
      • Roeselare, Bélgica
  • Canadá
    • Ontario
      • Toronto, Ontario, Canadá
    • Quebec
      • Greenfield Park, Quebec, Canadá
      • Sherbrooke, Quebec, Canadá
  • Espanha
      • Barcelona, Espanha
      • Madrid, Espanha
      • Valencia, Espanha
    • Vizcaya
      • Barakaldo, Vizcaya, Espanha
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos
    • Arizona
      • Phoenix, Arizona, Estados Unidos
    • California
      • Long Beach, California, Estados Unidos
      • San Diego, California, Estados Unidos
      • Santa Ana, California, Estados Unidos
    • Florida
      • Boca Raton, Florida, Estados Unidos
      • Delray Beach, Florida, Estados Unidos
      • Edgewater, Florida, Estados Unidos
      • Orlando, Florida, Estados Unidos
    • Georgia
      • Decatur, Georgia, Estados Unidos
    • Illinois
      • Chicago, Illinois, Estados Unidos
      • Springfield, Illinois, Estados Unidos
    • Kentucky
      • Paducah, Kentucky, Estados Unidos
    • Minnesota
      • Saint Paul, Minnesota, Estados Unidos
    • Mississippi
      • Olive Branch, Mississippi, Estados Unidos
    • Nevada
      • Las Vegas, Nevada, Estados Unidos
    • New Jersey
      • Berlin, New Jersey, Estados Unidos
      • Chester, New Jersey, Estados Unidos
      • Eatontown, New Jersey, Estados Unidos
      • Summit, New Jersey, Estados Unidos
      • Toms River, New Jersey, Estados Unidos
    • New York
      • Albany, New York, Estados Unidos
      • Brooklyn, New York, Estados Unidos
      • Latham, New York, Estados Unidos
      • Manhasset, New York, Estados Unidos
      • New Hyde Park, New York, Estados Unidos
    • Ohio
      • Cincinnati, Ohio, Estados Unidos
    • Oklahoma
      • Oklahoma City, Oklahoma, Estados Unidos
      • Tulsa, Oklahoma, Estados Unidos
    • Rhode Island
      • Providence, Rhode Island, Estados Unidos
    • Texas
      • Austin, Texas, Estados Unidos
      • Dallas, Texas, Estados Unidos
      • Houston, Texas, Estados Unidos
      • San Antonio, Texas, Estados Unidos
    • Vermont
      • Bennington, Vermont, Estados Unidos
    • Virginia
      • Charlottesville, Virginia, Estados Unidos
    • Wisconsin
      • Milwaukee, Wisconsin, Estados Unidos
  • Japão
      • Akashi, Japão
      • Akita, Japão
      • Azumino, Japão
      • Chiba, Japão
      • Fukui, Japão
      • Kyoto, Japão
      • Niigata, Japão
      • Osaka, Japão
      • Saga, Japão
      • Tokushima, Japão
      • Tokyo, Japão
  • Polônia
      • Lublin, Polônia
      • Scinawa, Polônia
      • Warszawa, Polônia
  • Reino Unido
      • Bath, Reino Unido
      • Brentford, Reino Unido
      • Brighton, Reino Unido
      • Glasgow, Reino Unido
    • East Sussex
      • Uckfield, East Sussex, Reino Unido

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

50 anos a 89 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Dobro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador de Placebo: Controle de placebo
Biológico: Human albumin 0.25%
Intravenous infusion every 2 weeks over 18 months
Experimental: IGIV, 10% at high dose (0.4 g/kg)
Biológico: Immune Globulin Intravenous (Human), 10% Solution
Intravenous infusion every 2 weeks over 18 months
Outros nomes:
  • IGIV, 10%
Experimental: IGIV, 10% at low dose (0.2 g/kg)
Biológico: Immune Globulin Intravenous (Human), 10% Solution
Intravenous infusion every 2 weeks over 18 months
Outros nomes:
  • IGIV, 10%

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline to Month 18 in Cognitive Subscale of the Alzheimer´s Disease Assessment Scale (ADAS-Cog)
Prazo: Baseline to 9 Months (actual time frame)
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
Prazo: Baseline to 9 Months (actual time frame)
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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
ADCS-Clinical Global Impression of Change (CGIC) at 18 Months
Prazo: Baseline to 9 Months (actual time frame)
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).
Baseline to 9 Months (actual time frame)
Change From Baseline to Month 18 in Neuropsychiatric Inventory (NPI)
Prazo: Baseline to 9 Months (actual time frame)
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.
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
Prazo: Baseline to 9 Months (actual time frame)
Baseline to 9 Months (actual time frame)
Change From Baseline to Month 18 in Logsdon Quality of Life in Alzheimer´s Disease (QOL-AD)
Prazo: Baseline to 9 Months (actual time frame)
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.
Baseline to 9 Months (actual time frame)
Change From Baseline to Month 18 in Impact of Alzheimer´s Disease on Caregiver Questionnaire (IADCQ)
Prazo: Baseline to 9 Months (actual time frame)
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.
Baseline to 9 Months (actual time frame)
Number of Participants Experiencing Study Product-related Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
Prazo: Throughout the study period: 18 Months
Throughout the study period: 18 Months
Number of Participants Experiencing Any AEs and/or SAEs
Prazo: Throughout the study period: 18 Months
Throughout the study period: 18 Months
Number of Infusions Temporally Associated With AEs and/or SAEs
Prazo: During or within 72 hours of completion of an infusion
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.
During or within 72 hours of completion of an infusion
Number of Infusions Associated With AEs and/or SAEs Occurring During or Within 7 Days of Completion of an Infusion
Prazo: During or within 7 days of completion of an infusion
During or within 7 days of completion of an infusion
Number of Infusions Causally Associated With AEs and/or SAEs
Prazo: Throughout the study period: 18 Months
Throughout the study period: 18 Months
Number of Infusions Discontinued, Slowed, or Interrupted Due to an AE
Prazo: Throughout infusions, approximately 2-5 hours
Throughout infusions, approximately 2-5 hours

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Baxalta now part of Shire

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

23 de janeiro de 2012

Conclusão Primária (Real)

16 de julho de 2013

Conclusão do estudo (Real)

16 de julho de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

20 de janeiro de 2012

Enviado pela primeira vez que atendeu aos critérios de CQ

31 de janeiro de 2012

Primeira postagem (Estimativa)

2 de fevereiro de 2012

Atualizações de registro de estudo

Última Atualização Postada (Real)

19 de maio de 2021

Última atualização enviada que atendeu aos critérios de controle de qualidade

30 de abril de 2021

Última verificação

1 de abril de 2021

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 161003
  • 2011-000914-21 (Número EudraCT)

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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