Effect of cladribine treatment on microglial activation in the CNS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Varsinais-Suomen hyvinvointialue

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Nervous System Diseases [C10]

Trial duration

16 Aug 2019 → ongoing

Decision date (initial)

2024-12-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519921-39-00

EudraCT number

2019-001960-31

ClinicalTrials.gov

NCT04239820

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the change in microglial cell activation in different brain areas (NAWM normal appearing grey matter and the chronic active/ smoldering (slowly expanding) lesions) before and after 18 months of treatment with cladribine evaluated with [11C]PK11195-PET-imaging.

Secondary objectives 8

1. To compare the change in microglial cell activation in different brain areas (normal appearing white matter (NAWM), normal appearing grey matter (NAGM) and the chronic active/ smoldering lesions) before and after 18 months of treatment with cladribine evaluated with QSM-MRI.
2. To evaluate the total lesion load of the white matter MS plaques at different time points using MRI
3. To measure total brain, white matter (WM) and gray matter (GM) volumes using MRI at different time points of the study
4. To determine MD (mean diffusivity) and FA (fractional anisotropy) using DTI (diffusion tensor imaging at different time points of the study
5. To correlate the baseline microglial activation status to the clinical outcome parameters at the end of the study (18 months) to evaluate whether high microglial activation is predictive of higher likelihood of progression and other measures of disability.
6. To correlate the baseline microglial activation status to the MRI parameters
7. To compare microglial activation at baseline in the study group to microglial activation in a group of age-matched previously imaged healthy controls
8. To compare microglial activation in the study group to microglial activation in an independent group of previously imaged age-matched untreated MS-patients.

Conditions and MedDRA coding

Multiple Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Signing the informed consent form
2. Cladribine treatment is planned and indicated and is according to label
3. 35-55 years of age at the time of signing the research informed consent form
4. RRMS diagnosis in accordance with McDonald 2017 criteria

Exclusion criteria 16

1. Patients with other neurodegenerative disease than MS
2. Abnormal lymphocyte counts
3. Patients with human immunodeficiency virus (HIV).
4. Patients with active chronic infection (tuberculosis or hepatitis).
5. Patients with active malignancy.
6. Patients with moderate or severe renal impairment (creatinine clearance <60 mL/min)
7. Patients that are pregnant or breast-feeding
8. Corticosteroid treatment within 4 weeks of imaging
9. Patients with significant abnormal findings other than MS in the screening MRI.
10. Patients with claustrophobia, or a history of moderate to severe anxiety disorder or panic attacks (which could potentially lead to preterm termination of the imaging)
11. Contraindication to PET scan investigations
12. Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study.
13. Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans.
14. Patients with previous alemtuzumab administration
15. Patients with less than 6 months since previous administration of ocrelizumab or rituximab (or with abnormal B-cell counts)
16. Patients with less than 1 month since previous administration of other DMT

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in microglial cell activation in different brain areas (NAWM normal appearing grey matter and the chronic active/ smoldering (slowly expanding) lesions) before and after 18 months of treatment with cladribine evaluated with [11C]PK11195-PET-imaging.

Secondary endpoints 8

1. Change in microglial cell activation in different brain areas (normal appearing white matter (NAWM), normal appearing grey matter (NAGM) and the chronic active/ smoldering lesions) before and after 18 months of treatment with cladribine evaluated with QSM-MRI.
2. Change in the total lesion load of the white matter MS plaques at different time points using MRI
3. Change in total brain, white matter (WM) and gray matter (GM) volumes using MRI at different time points of the study
4. Change in MD (mean diffusivity) and FA (fractional anisotropy) using DTI (diffusion tensor imaging at different time points of the study
5. Correlation of the baseline microglial activation status to the clinical outcome parameters at the end of the study (18 months) to evaluate whether high microglial activation is predictive of higher likelihood of progression and other measures of disability.
6. Correlation of the baseline microglial activation status to the MRI parameters
7. Different microglial activation at baseline in the study group when compared to microglial activation in a group of age-matched previously imaged healthy controls
8. Different microglial activation in the study group to microglial activation in an independent group of previously imaged age-matched untreated MS-patients.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Varsinais-Suomen hyvinvointialue

Sponsor organisation

Varsinais-Suomen hyvinvointialue

Address

Kiinamyllynkatu 4-8

City

Turku

Postcode

20520

Country

Finland

Scientific contact point

Organisation

Varsinais-Suomen hyvinvointialue

Contact name

Laura Airas

Public contact point

Organisation

Varsinais-Suomen hyvinvointialue

Contact name

Laura Airas

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 5 files

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

Application history

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