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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03234686




Registration number
NCT03234686
Ethics application status
Date submitted
23/07/2017
Date registered
31/07/2017
Date last updated
24/01/2018

Titles & IDs
Public title
Deferiprone to Delay Dementia (The 3D Study)
Scientific title
Deferiprone to Delay Dementia (The 3D Study): a Clinical Proof of Concept Study
Secondary ID [1] 0 0
DEF001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 0 0
Prodromal Alzheimer's Disease 0 0
Mild Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Deferiprone 600mg delayed release tablets
Treatment: Drugs - Placebo Oral Tablet

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

Placebo Comparator: Placebo - Patients will receive matching placebo tablets designed to mimic the experimental treatment, twice daily


Treatment: Drugs: Deferiprone 600mg delayed release tablets
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.

Treatment: Drugs: Placebo Oral Tablet
The placebo will mimic the Deferiprone arm in every way, except the placebo will not include the active ingredient

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
12 months

Eligibility
Key inclusion criteria
1. 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.

2. 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.

3. Weight between 40 and 120 kg

4. Have an available caregiver

5. Have = 6 years of education (any) and able to follow testing instructions.

6. Have visual and auditory acuity sufficient to perform neuropsychological testing.

7. Have prior evidence of AD pathology, by a positive amyloid assessment, or amyloid PET
scan.

8. 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

9. Subjective or clinical history of retrospective cognitive decline =6 months

10. Evidence of mild symptomatology, as defined by a screening MMSE score of = 20 points

11. Meet National Institute on Ageing/Alzheimer's Association Diagnostic Guidelines for
Alzheimer's Disease (NIAAA) research criteria for mAD or pAD

12. If receiving medication for symptomatic AD, have a stable dosing regimen for 3 months
prior to screening.

13. Females of Child Bearing Potential (FCBP) must have confirmed negative serum pregnancy
test within the 21 days prior to randomization.

14. 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).
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant haematological disorder, including moderate or severe anaemia
(blood haemoglobin <110 g/L, WHO definition)

2. Iron deficiency (serum ferritin < 10 ng/mL)

3. Clinically significant abnormal haematological results (sufficiently outside the
normal range to warrant further investigation). Mild anaemia (haemoglobin =110 g/L) is
not an exclusion.

4. Clinically significant abnormal renal or liver function results (sufficiently outside
the normal range to warrant further investigation)

5. 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

6. 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

7. History of any stroke in the past 2 years, or transient ischemic attack within the
last 6 months

8. History of persistent neurologic deficit, intracranial tumour or structural brain
damage

9. History of infection that could affect brain function (eg HIV and syphilis)

10. Autoimmune disorders that potentially cause progressive neurologic disease with
associated cognitive deficits, such as but not limited to multiple sclerosis, lupus

11. 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)

12. A history of relapsing neutropenia.

13. Presence of agranulocytosis or with a history of agranulocytosis

14. Known hypersensitivity to DFP or excipients.

15. Alcohol and/or substance abuse

16. 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.

17. Active major medical illness

18. FCBP not using adequate method of contraception or who is pregnant or nursing

19. Inability to provide informed consent

20. Participation in another clinical trial within 3 months prior to inclusion in the
study

21. Subjects for whom MRI is contraindicated (severe claustrophobia, pacemaker,
incompatible surgical material, unmovable electronic pump implant)

22. Negative amyloid PET scan or CSF in the last 2 years.

23. Hospital Anxiety and Depression Scale (scores > 8/21 are disqualified).

24. 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.

25. Subject has planned surgery which does not permit regular blood tests with the
interval between tests not exceeding 10 days from the scheduled visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Neuroscience Trials Australia
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03234686
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tina Soulis
Address 0 0
Country 0 0
Phone 0 0
(03) 9035 7158
Fax 0 0
Email 0 0
athina.soulis@unimelb.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03234686