Cladribine for the treatment of secondary progressive MS - randomized, double-blind, placebo-controlled study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Psychiatrii I Neurologii

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Jan 2025 → ongoing

Decision date (initial)

2025-01-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2024-516992-33-02

EudraCT number

2022-000036-32

ClinicalTrials.gov

NCT05961644

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The aim of the study is to evaluate the efficacy and safety of subcutaneously administered cladribine compared with placebo in patients with secondary progressive multiple sclerosis (SPMS) who have had progression in the last 24 months and no relapses within 12 months. Patients with or without MRI disease activity (patients with gadolinium enhancement lesions [T1Gd +] or new / increasing T2 lesions) will be enrolled in the study. The primary efficacy endpoint for subcutaneous administration of cladribine in SPMS patients will be slowing of brain volume loss relative to placebo.

Secondary objectives 1

1. 1. Evaluation of the usefulness of QSM imaging for the assessment of disease activity in the progressive phase 2. Searching for protein and imaging biomarkers for monitoring treatment in the progressive phase

Conditions and MedDRA coding

Multiple sclerosis secondary progressive form

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Written informed consent to participate in the study 2. Diagnosis of SPMS based on the 2017 McDonald criteria, with a relapsing-remitting course at the onset of the disease 3. History of progressive neurological deterioration within at least 24 months: Increase in EDSS score by at least 1 point if EDSS ≤ 5 and by at least 0.5 point if EDSS> 5. A summary written by the researcher explaining why he thinks the patient has progressive disease for at least 24 months. 4. No clinical relapses in the last 12 months 5. Baseline EDSS ≥ 3.5 and ≤ 7.5 6. Age 30-65 years 7. Time from first symptoms at least 10 years 8. For women of childbearing potential: a written declaration of discontinuation of heterosexual intercourse or use of contraception in the study and for at least 6 months after the last dose as defined below: a. The woman must stop heterosexual intercourse or use a contraceptive method with a failure rate <1% per year during treatment. Women are also not allowed to donate eggs during this period. b. A woman of childbearing potential is a woman who has had her first menstrual period, is premenopausal (uninterrupted period of at least 12 months without menstruation) and is not permanently sterile due to surgery (removal of the ovaries, fallopian tubes and / or uterus) or any other reason. found by the researcher. c. Examples of contraception with a failure rate <1% per year are bilateral tubal ligation, partner sterilization, hormonal contraception to suppress ovulation, hormone-secreting IUDs or copper IUDs. d. Hormonal contraception must be used in conjunction with a barrier method. e. Temporary abstinence, such as using a calendar method, is not an acceptable form of contraception. 9. For men: a written declaration to stop heterosexual intercourse in the study and for at least 6 months after the last dose, or to use condoms and contraception in female partners during this period as described above. In addition, statements on not donating semen during the study and for 6 months after the last dose of the drug. 10. Possibility of meeting the requirements of the test protocol in the opinion of the researcher.

Exclusion criteria 1

1. 1. Lack of consent to participate in the study 2. History of cladribine treatment regardless of indication 3. Hypersensitivity to any component of the investigational drug 4. The need to use other immunomodulating or immunosuppressive drugs, including drugs used in secondary progressive MS, e.g. interferon beta-1b, mitoxantrone, siponimod 5. Contraindications for performing magnetic resonance imaging 6. Pregnancy and the period of breastfeeding 7. Lack of consent to the use of effective methods of contraception as defined in the inclusion criteria 8. Diseases of the nervous system (brain or spinal cord tumors, stroke or spinal cord, brain or spinal cord injury, encephalomyelitis, vitamin B12 deficiency, other than multiple sclerosis demyelinating diseases of the central nervous system) 9. Serious accompanying diseases (e.g. cancer, liver and / or kidney failure, heart failure II and III according to NYHA) or other diseases which, in the opinion of the investigator, could threaten the patient's safety in the study or prevent compliance with the requirements of the study protocol 10. Disease relapse <12 months after screening visit 11. Chronic treatment with steroids or immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) <6 months prior to study entry 12. Disease-modifying therapies: a. Interferons, glatiramer acetate, and dimethyl fumarate must be withdrawn prior to inclusion in the study; they do not require a transition period; b. teriflunomide, fingolimod, natalizumab must be discontinued at least 6 weeks prior to study enrollment; for teriflunomide, the SmPC dropout procedure must be followed if the patient requires enrollment in the study between 2-4 weeks after withdrawal;c. ocrelizumab, mitoxantrone, and alemtuzumab must be discontinued for at least 12 months prior to study enrollment. 13. Relapsing-remitting MS 14. Primary progressive form of MS 15. HBV or HCV infection (positive HBV, positive anti-HBc antibodies or positive anti-HCV antibodies) 16. HIV infection or HIV screening positive (anti-HIV 1/2 antibodies, p24 antigen) 17. Active or latent tuberculosis: a positive QuantiFERON TB Gold (QFT) test during screening or in the 3 months prior to screening (inconclusive test should be repeated; two inconclusive tests are considered positive) 18. Other infections that may worsen with cladribine therapy. 19. Lymphopenia during screening (<1,000 / μl), neutrocytopenia (<1,500 / μl) or thrombocytopenia (<150,000 / μl) 20. Clinical significant abnormalities in the ECG examination according to the researcher's opinion 21. Alcohol or drug abuse in the last 12 months 22. Positive serum pregnancy test during screening 23. History of bone marrow or other organ transplantation 24. Treatment with immunoglobulins or plasmapheresis within the 3 months prior to randomization 25. Treatment with another Investigational medicinal product or medical device in the 6 months prior to randomization 26. At least one abnormal test: a.Creatinine> 1.5 x ULN (ULN; may be repeated if 1.5-2.0 x ULN) b. ALT or AST> 2 x ULN (may be repeated if 1.5-3 x ULN) c. Total Bilirubin> 1.5 x ULN (may be repeated if 1-3 x ULN) d. Hemoglobin <9.5 g / dL (can be repeated if 9-9.4 g / dL) 27. Patient is not fully vaccinated against COVID-19, i.e. at least 6 weeks have not elapsed since the last dose of vaccination. 28. Vaccination with any vaccine within less than 6 weeks 29. The patient has not been screened for neoplasms or the tests performed suggest neoplasm or further tests for neoplasm (chest X-ray PA + side for women and men, mammography or ultrasound of breasts for women, cytology for women, PSA for men). 30. Lack of measurable serum levels of anti-varicella / herpes zoster antibodies. 31. Anticoagulant therapy (oral or parenteral) or anti-platelet therapy other than acetylsalicylic acid.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent brain volume change from last cladribine dose (week 26) to end of study (week 122).

Secondary endpoints 1

1. 1.Time to 24-week confirmed composite progression of disability defined as the occurrence of any of the following events: an increase in EDSS score, in time of Timed 25-Foot Walk and 9-Hole Peg Test. 2.Change from baseline in cognitive function (CANTAB, CVLT, SDMT) and quality of life (MSQeL-54) 3.Neuroimaging: number of Gd+ lesions, new T2 lesions, QSM rim+ lesions, volume of T1 lesions (black holes), volume of cervical spinal cord in T1; 4. Serum level of NfL, GFAP, oligoclonal bands presence

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Psychiatrii I Neurologii

Sponsor organisation

Instytut Psychiatrii I Neurologii

Address

Ul. Jana III Sobieskiego 9

City

Warsaw

Postcode

02-957

Country

Poland

Scientific contact point

Organisation

Instytut Psychiatrii I Neurologii

Contact name

II Klinika Neurologii

Public contact point

Organisation

Instytut Psychiatrii I Neurologii

Contact name

II Klinika Neurologii

Sponsor responsibilities

Article 77 implementation

Instytut Psychiatrii I Neurologii

Locations

1 EU/EEA country · 2 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 7 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