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.
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. Participants will return to the centre on Weeks 13, 26, 38, 52 (or early termination) to undertake a neurological examination as well as an assessment of blood samples taken at the visit. Participants must also attend weekly blood tests. SAE's, AE's and changes to concomitant medications will be observed and evaluated throughout the study. Each study visit will have a 7-day window after the due date to account for scheduling conflicts/holidays/weekends. Participants will be given additional study product to account for the 7-day window. Participants must attend the weekly pathology visits with a 3-day window of the scheduled date or risk termination from the trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
The active substance, Deferiprone, is a member of the 3-hydroxypyrid-4-one class of iron chelators, which have a high affinity for ferric iron, binding it in a 3:1 (Deferiprone:iron) molar ratio.
The placebo will mimic the Deferiprone arm in every way, except the placebo will not include the active ingredient
KaRa Institute of Neurological Diseases
Macquarie Park, New South Wales, Australia
Hunter New England Local Health District
Waratah, New South Wales, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Efficacy of Deferiprone
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
Time frame: 12 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Safety and tolerability will be assessed by the incidence and severity of AEs and changes from baseline of all relevant parameters, including clinical laboratory values, vital signs, ECG and other safety biomarkers. Severity of AEs will be assessed according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03. All subjects will be monitored for AEs until resolution.
Time frame: 12 months
Brain Iron Levels
Using MRI to compare iron levels in various brain regions of the Deferiprone and placebo treatment groups at baseline and 12 months.
Time frame: 12 months
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Masking
DOUBLE
Enrollment
81
Alfred Hospital
Melbourne, Victoria, Australia
NeuroCentrix
Noble Park, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Australian Alzheimer's Research Foundation
Nedlands, Western Australia, Australia