Deferiprone to Delay Dementia (The 3D Study): a Clinical Proof of Concept Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 8
- 主要终点
- Efficacy of Deferiprone
研究概览
简要总结
This study is a phase 2, randomised, placebo-controlled, multicentre study to investigate the safety and efficacy of Deferiprone in participants with Prodromal Alzheimer's Disease (pAD) and Mild Alzheimer's Disease (mAD). In this phase 2 study, the investigators aim to determine whether Deferiprone (15 mg/kg BID orally) slows cognitive decline in Alzheimer's patients. As secondary outcomes, safety and iron levels in the brain will be evaluated.
详细描述
This Phase II study is designed as a randomised, double-blinded, placebo controlled, multi-centre study for subjects with evidence of amyloid positive pAD or mAD.
Participants will be assigned randomly to two groups (Group 1 Deferiprone (15mg/kg BID orally), Group 2: Placebo). Participants will have a 2 in 3 chance to be placed in the Deferiprone group.
The study will enrol approximately 171 participants over 4 sites in Australia. The overall duration for patients will be 54 weeks. This includes a 55-day screening period, and visits on Day 1, weeks 13, 26, 38,52, and a two-week follow-up visit.
Participants will be screened for the study after signing the approved informed consent form. As part of the 55-day screening phase, subjects will undertake an extensive medical and neurological assessments as well as a PET scan.
At the baseline visit, following the screening phase, blood and urine will be taken for safety monitoring and for measuring APOE-4 gene status. Baseline signs and symptoms will be collected. An MRI will be performed All patients will start with study medication at the Baseline visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide written informed consent in accordance with federal, local and institutional guidelines. For subjects unable to provide written consent, consent will be provided by the Person Responsible per local regulations.
- •Age ≥65 years, or ≥55 years if they have been diagnosed by a psychiatrist or neurologist with dementia, or if they have a validated previous positive amyloid PET scan.
- •Weight between 40 and 120 kg
- •Have an available caregiver
- •Have ≥ 6 years of education (any) and able to follow testing instructions.
- •Have visual and auditory acuity sufficient to perform neuropsychological testing.
- •Have prior evidence of AD pathology, by a positive amyloid assessment, or amyloid PET scan.
- •Demonstrate abnormal memory function in the last 6 months or at screening: International Shopping List Test (ISLT) >1.5 SD below the age adjusted mean
- •Subjective or clinical history of retrospective cognitive decline ≥6 months
- •Evidence of mild symptomatology, as defined by a screening MMSE score of ≥ 20 points
- •Meet National Institute on Ageing/Alzheimer's Association Diagnostic Guidelines for Alzheimer's Disease (NIAAA) research criteria for mAD or pAD
- •If receiving medication for symptomatic AD, have a stable dosing regimen for 3 months prior to screening.
- •Females of Child Bearing Potential (FCBP) must have confirmed negative serum pregnancy test within the 21 days prior to randomization.
- •FCBP and male subjects who are sexually active with FCBP must agree to use highly effective contraception during the study and until 90 days after the last dose of treatment (for sexually active male participants whose partners are FCBP) or until 30 days after the last dose of treatment (for women of childbearing potential participants).
排除标准
- •Clinically significant haematological disorder, including moderate or severe anaemia (blood haemoglobin <110 g/L, WHO definition)
- •Iron deficiency (serum ferritin < 10 ng/mL)
- •Clinically significant abnormal haematological results (sufficiently outside the normal range to warrant further investigation). Mild anaemia (haemoglobin ≥110 g/L) is not an exclusion.
- •Clinically significant abnormal renal or liver function results (sufficiently outside the normal range to warrant further investigation)
- •Presence of non-AD condition that may affect cognition, such as but not limited to Parkinson's Disease (PD), normal pressure hydrocephalus, sleep apnoea requiring O2 treatment
- •Clinically evident vascular disease that could potentially affect the brain, such as but not limited to significant carotid or vertebral stenosis, aortic aneurysm, cerebral haemorrhage
- •History of any stroke in the past 2 years, or transient ischemic attack within the last 6 months
- •History of persistent neurologic deficit, intracranial tumour or structural brain damage
- •History of infection that could affect brain function (eg HIV and syphilis)
- •Autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits, such as but not limited to multiple sclerosis, lupus
- •Major psychiatric illness (depression is acceptable if patient has not had an episode within the past year or is considered in remission or controlled by treatment)
- •A history of relapsing neutropenia.
- •Presence of agranulocytosis or with a history of agranulocytosis
- •Known hypersensitivity to DFP or excipients.
- •Alcohol and/or substance abuse
- •MRI evidence of clinically-significant cerebrovascular pathology. Focal white matter lesions, ≤ 2 lacunar infarcts in non-critical sites and other minor pathology assessed by the investigator to not be causing the current cognitive impairment, will not lead to exclusion.
- •Active major medical illness
- •FCBP not using adequate method of contraception or who is pregnant or nursing
- •Inability to provide informed consent
- •Participation in another clinical trial within 3 months prior to inclusion in the study
- •Subjects for whom MRI is contraindicated (severe claustrophobia, pacemaker, incompatible surgical material, unmovable electronic pump implant)
- •Negative amyloid PET scan or CSF in the last 2 years.
- •Hospital Anxiety and Depression Scale (scores > 8/21 are disqualified).
- •Subject cannot commit to regular blood tests with the interval between tests not exceeding 10 days from the scheduled visit for the duration of the study.
- •Subject has planned surgery which does not permit regular blood tests with the interval between tests not exceeding 10 days from the scheduled visit.
研究组 & 干预措施
Deferiprone
Patients will orally receive the equivalent 15 mg/kg of 600mg delayed release Deferiprone tablets twice daily.
干预措施: Deferiprone 600mg delayed release tablets (Drug)
Placebo
Patients will receive matching placebo tablets designed to mimic the experimental treatment, twice daily
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Efficacy of Deferiprone
时间窗: 12 months
Comparison of the efficacy of Deferiprone (15 mg/kg) administered orally twice a day with a matching placebo in subjects with pAD (MCI with brain amyloid pathology) or mAD at 12 months relative to baseline. This will be measured by a series of paper and electronic assessments called the NTB
次要结局
- Brain Iron Levels(12 months)
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(12 months)