Mild Cognitive ImpairmentPhase 2NCT03234686
Deferiprone to Delay Dementia (The 3D Study)
A Phase 2 study testing Deferiprone 600mg delayed release tablets in people with Mild Cognitive Impairment and Prodromal Alzheimer's Disease, run by Neuroscience Trials Australia at 8 sites in Australia.
Trial 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). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Mild Cognitive Impairment, Prodromal Alzheimer's Disease, Mild Alzheimer's Disease
- What is being tested?
- Deferiprone 600mg delayed release tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 8 sitesAustralia
- Study dates
- 19 Jan 2018to 23 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Australia8 sites
Box Hill Hospital
Box Hill, Victoria, 3128
Austin Health
Heidelberg, Victoria, 3084
KaRa Institute of Neurological Diseases
Macquarie Park, New South Wales, 2113
Alfred Hospital
Melbourne, Victoria, 3004
Australian Alzheimer's Research Foundation
Nedlands, Western Australia, 6009
NeuroCentrix
Noble Park, Victoria, 3174
Royal Melbourne Hospital
Parkville, Victoria, 3050
Hunter New England Local Health District
Waratah, New South Wales, 2298
About this study
Official title: Deferiprone to Delay Dementia (The 3D Study): a Clinical Proof of Concept Study
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.
Read the detailed description
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.
- Being tested
- Deferiprone 600mg delayed release tablets, Placebo Oral Tablet
- Keywords
- Dementia, Alzheimer's Disease
- Medical subject headings
- Cognitive Dysfunction, Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deferiprone 600mg delayed release tabletsDrug
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.
Placebo Oral TabletDrug
The placebo will mimic the Deferiprone arm in every way, except the placebo will not include the active ingredient
| Study group | Role | What they receive |
|---|---|---|
| Deferiprone | Experimental | Patients will orally receive the equivalent 15 mg/kg of 600mg delayed release Deferiprone tablets twice daily. Receives: Drug: Deferiprone 600mg delayed release tablets |
| Placebo | Placebo comparator | Patients will receive matching placebo tablets designed to mimic the experimental treatment, twice daily Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (2)
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.
Measured: 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start19 Jan 2018
- Primary completion1 Jan 2023
- Study completion23 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuroscience Trials Australia
- Sponsor type
- University, hospital or other
- Collaborators
- The Florey Institute of Neuroscience and Mental Health
- Responsible party
- Sponsor
- Investigators
- Ashley I. Bush, Principal investigator, The Florey Institute of Neuroscience and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234686
- Sponsor's protocol ID
- DEF001
- Status last verified
- Jun 2024
- First submitted
- 23 Jul 2017
- Last updated
- 3 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39495531
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deferiprone to Delay Dementia (The 3D Study): a Clinical Proof of Concept Study
- ClinicalTrials.gov ID
- NCT03234686
- Acronym / sponsor ID
- DEF001
- Keywords
- Dementia, Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Neuroscience Trials AustraliaUniversity, hospital or other
- Collaborators
- The Florey Institute of Neuroscience and Mental Health
- Study start
- 19 Jan 2018 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 23 Feb 2023 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferiprone | Experimental | Drug: Deferiprone 600mg delayed release tabletsPatients will orally receive the equivalent 15 mg/kg of 600mg delayed release Deferiprone tablets twice daily. |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPatients will receive matching placebo tablets designed to mimic the experimental treatment, twice daily |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deferiprone 600mg delayed release tabletsThe 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. | Drug | Deferiprone |
| Placebo Oral TabletThe placebo will mimic the Deferiprone arm in every way, except the placebo will not include the active ingredient | Drug | Placebo |
Primary outcome
Efficacy of Deferiprone
Time frame: 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
2 secondary outcomes
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: 12 months
Brain Iron Levels
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Derived from this study: PubMed 39495531Ayton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashley I. Bush principal investigator
The Florey Institute of Neuroscience and Mental Health
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Deferiprone 600mg delayed release tablets in people with Mild Cognitive Impairment and Prodromal Alzheimer's Disease, run by Neuroscience Trials Australia at 8 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Deferiprone (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03234686, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.