Iron chelation in the prevention of secondary degeneration after stroke

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Jun 2022 → 22 Apr 2025

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministry of Health (PHRC Inter Régional 2019 – N° PHRCI-19-056)

External identifiers

EU CT number

2024-514230-20-00

EudraCT number

2021-002219-69

ClinicalTrials.gov

NCT05111821

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare, in patients with proximal occlusion of the sylvian artery, the effect of prolonged treatment (6 months) with defereriprone (Ferriprox®) given daily at a low dose (30mg/Kg/d) from J3-J5, on the evolution of the iron accumulation (95th percentile of R2* values) between an initial MRI (J5) and at 6 months within the homolateral black substance and initially spared by the infarction, compared to the values measured without treatment in our previous work.

Secondary objectives 2

1. To compare the effect of prolonged treatment (6 months) with defereriprone (Ferriprox®) given daily at low dose (30mg/Kg/d) from J3-J5, on : - evolution of iron accumulation (95th percentile of R2* values) between an initial MRI (J5) and 6 months within the homolateral thalamus and initially spared by the infarction, compared to the values measured without treatment in our previous work. - clinical performance measured at 6 months (and 3 months) between patients treated with defereriprone and untreated patients (effect difference and confidence interval of difference).
2. To compare voxel to voxel the evolution of the iron load (95th percentile of R2* values and QSM measurements) between an initial MRI (J5) and at 6 months after a sylvian infarction within the black substance, thalamus and the whole brain, between patients treated with defereriprone (experimental group) and untreated patients (control group)

Conditions and MedDRA coding

Stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - Patient older than 18 years old.
2. - Covered by a social insurance
3. - With a stroke involving the deep territory of the middle cerebral artery (including at least half of the volume of the striatum) due to occlusion of the carotid artery or of proximal M1 or M2 segments. The artery can be occluded when the patient is admitted at the acute phase or already recanalized as soon as the striatum is involved
4. - Absolute neutrophil count ≥1.5 x109/L
5. - For women of childbearing potential, negative β HCG test and effective contraception (oestroprogestative contraception, intra-uterine device, bilateral salpingectomy) to be continued 6 months after the last administration of deferiprone
6. - Men whose partner provides a highly effective contraception or who accept to use a contraception method (condom) while treated by deferiprone and to continue 90 days after the last administration of deferiprone
7. - Written informed consent dated and signed prior to the beginning of any procedures related to the clinical trial. Patients unable to give their personal consent (severe aphasia, impaired understanding or attention induced by the infarction) may be included with the consent by a trusted person provided in article L. 1111-6, by the family or by a person who has a close and stable relationship with the person concerned. The person concerned is informed as soon as possible and his consent is sought during visit at 3 month or 6 month if he regains his capacity to consent. These patients may be included because the treatment may be provided by the caregiver, or a home nurse for patients alone or for whom the caregiver is unable to follow the treatment. Most severe patients, in rehabilitation structure will have support for taking treatment and monitoring it

Exclusion criteria 22

1. - Contraindication to MRI
2. - Pregnant or breast feeding women
3. - Inability to swallow correctly (required for oral treatment)
4. - History of symptomatic cerebral infarct or hemorrhage
5. - Pre-stroke modified Rankin Scale [mRS] score>2
6. - History of severe cognitive impairment (dementia)
7. - History of recent (within the past 6 months) and evolving psychiatric disorders matching to axis 1 of the DSM-IV criteria
8. - History of stroke directly involving substantia nigra or thalamus
9. - Microbleed, or past hematoma involving substantia nigra; past hematoma involving thalamus
10. - PH1 or PH2 hemorrhagic transformation
11. - Hypersensitivity to Deferiprone or any of the excipients mentioned in section 6.1 of the Summary of Product characteristics of Ferriprox
12. - Patients with agranulocytosis or with a history of agranulocytosis
13. - Patients with history of relapsing neutropenia
14. - Patient with immunosuppression condition
15. - Due to the risk of agranulocytosis caused by Deferiprone and the unknown mechanism by which this agranulocytosis is induced, combining Deferiprone with other medicinal products known to cause agranulocytosis will not be allowed. Such medicinal products include clozapine as well as some NSAIDs (e.g. Phenylbutazone or Metamizole), antithyroid agents, sulfonamide antibiotics or metothrexate
16. - Patients with anaemia (regardless of latter aetiology) or a history of another haematological disease
17. - Participation in another drug study (Investigational medical product) within 1 month prior to inclusion in the study and within 1 month after the final evaluation
18. - Patient with history of Parkinson's disease symptoms (tremor at rest, bradykinesia, rigidity, postural dysfunction, gait abnormalities, loss of balance), exclusion criterion due to the association of Deferiprone with worse outcome in patients with early Parkinson's disease according to the FAIRPARK-II Study Group
19. - Kidney or liver failure
20. - Patient in an emergency situation
21. - Patient under permanent guardianship
22. - Patient subject to a safeguard measure of justice

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Variation of iron as measured by R2* (95th percentile) between the baseline MRI (performed before day 5) and the 6 month MRI, within the substantia nigra ipsilateral to stroke in the group of patients randomized to receive Deferiprone

Secondary endpoints 3

1. The variation of iron as measured by R2* (95th percentile) between the baseline MRI (performed before day 5) and the 6 month MRI, within the thalamus ipsilateral to stroke (whole thalamus and median nucleus) in the group of patients randomized to receive Deferiprone
2. The variation of R2* and of values from quantitative susceptibility mapping (QSM) between the baseline MRI (performed before day 5) and the 6 month MRI with a voxel-by-voxel quantification in patients randomized to receive Deferiprone versus those who will not receive Deferiprone
3. The clinical scores at 3 months and 6 months in patients randomized to receive Deferiprone and in patients from the control group: functional outcome assessed by the upper limb Fugl-Meyer scale, the Box and Block test and the modified Rankin scale (mRS); cognitive outcome assessed by the Montreal cognitive assessment (MoCA), and mood disorders assessed by the center for epidemiologic studies depression scale (CESD) and the generalized anxiety disorder scale (GAD-7)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Co-ordinating Investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Co-ordinating Investigator

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications