Deferiprone to Delay Dementia (The 3D Study)

NCT03234686 | Completed Phase 2

• 1 other identifier: DEF001
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Mild Cognitive Impairment; Prodromal Alzheimer's Disease; Mild Alzheimer's Disease

Keywords

Dementia; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  12 months

• Brain Iron Levels

  12 months

Other Outcomes (4)

• The effect of Deferiprone on the episodic memory, executive function and attention composites

  12 months

• The Association with Iron levels in the Brain and Cognitive Decline

  12 months

• The Potential for Brain Iron Load to be Used to Stratify Responsiveness to Deferiprone

  12 months

Study Arms (2)

Deferiprone

EXPERIMENTAL

Patients will orally receive the equivalent 15 mg/kg of 600mg delayed release Deferiprone tablets twice daily.

Drug: Deferiprone 600mg delayed release tablets

Placebo

PLACEBO COMPARATOR

Patients will receive matching placebo tablets designed to mimic the experimental treatment, twice daily

Drug: Placebo Oral Tablet

Interventions

Deferiprone 600mg delayed release tablets DRUG

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.

Deferiprone

Placebo Oral Tablet DRUG

The placebo will mimic the Deferiprone arm in every way, except the placebo will not include the active ingredient

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 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
• Active major medical illness

Sponsors & Collaborators

• Neuroscience Trials Australia: lead
• The Florey Institute of Neuroscience and Mental Health: collaborator

Study Sites (8)

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales, 2113, Australia

Location

Hunter New England Local Health District

Waratah, New South Wales, 2298, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

NeuroCentrix

Noble Park, Victoria, 3174, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• Ayton S, Barton D, Brew B, Brodtmann A, Clarnette R, Desmond P, Devos D, Ellis KA, Fazlollahi A, Fradette C, Goh AMY, Kalinowski P, Kyndt C, Lai R, Lim YY, Maruff P, O'Brien TJ, Rowe C, Salvado O, Schofield PW, Spino M, Tricta F, Wagen A, Williams R, Woodward M, Bush AI. Deferiprone in Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2025 Jan 1;82(1):11-18. doi: 10.1001/jamaneurol.2024.3733.

  PMID: 39495531 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Dementia; Alzheimer Disease

Interventions

Deferiprone

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ashley I. Bush

  The Florey Institute of Neuroscience and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2017
• First Posted: July 31, 2017
• Study Start: January 19, 2018
• Primary Completion: January 1, 2023
• Study Completion: February 23, 2023
• Last Updated: July 3, 2024

Record last verified: 2024-06

Locations

AU (8)