Investigating the role of genetic factors in relapsing multiple sclerosis

Interventional Not Pharmacological Study to Investigate the Role of ADA in Multiple Sclerosis PatientsTreated With an Immune-Reconstitution Therapy (2-CdA)

This study is testing how certain genetic factors might affect how well people with relapsing multiple sclerosis respond to a specific treatment called Cladribine.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Neuromed IRCCS (other)
• Drugs / interventions: natalizumab, alemtuzumab, ocrelizumab, methotrexate, cyclophosphamide
• Locations: 1 site (Pozzilli, Isernia)
• Trial ID: NCT04121065 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the impact of adenosine deaminase (ADA) single nucleotide polymorphisms (SNPs) on patients with relapsing multiple sclerosis (RMS). It focuses on understanding how these genetic variations may influence treatment responses, particularly in patients receiving immune reconstitution therapy with Cladribine (2-CdA). By analyzing blood samples from eligible participants, the study seeks to uncover potential links between genetic factors and the effectiveness of MS therapies. The findings could help tailor more effective treatment strategies for RMS patients.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with highly active relapsing multiple sclerosis who are eligible for treatment with Cladribine.

Not a fit: Patients with a history of certain immunosuppressive therapies or those with active infections such as hepatitis or HIV may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized treatment approaches for patients with relapsing multiple sclerosis, improving their outcomes.

How similar studies have performed: Other studies have shown promising results in understanding genetic influences on treatment responses in multiple sclerosis, suggesting this approach may yield valuable insights.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects ≥ 18 years old
2. Subjects candidate to be treated with Cladribine (2-CdA) according to clinical practice and meeting the SmPc requirements:

   * Body weight ≥ 40 Kg
   * Highly active RMS as defined by: One relapse in the previous year and at least 1 T1 Gd+ lesion or 9 or more T2 lesions, while on therapy with other disease modifying drugs (DMDs); two or more relapses in the previous year, whether on DMD treatment or not;
3. Normal lymphocyte count (absolute values 1.0-3.0×109/l) according to Cladribine local labelling;
4. EDSS score ≤5.0.

Exclusion Criteria:

1. Previous exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab;
2. Positive hepatitis C or hepatitis B surface antigen test and/or hepatitis B core antibody test for IgG and/or IgM;
3. Current or previous history of immune deficiency disorders including a positive human immunodeficiency virus (HIV) result;
4. Currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids;
5. History of tuberculosis, presence of active tuberculosis, or latent tuberculosis;
6. Evidence or suspect of PML in MRI;
7. Active malignancy or history of malignancy.
8. Pregnant or lactating women
9. Currently receiving interferon

Where this trial is running

Pozzilli, Isernia

• IRCCS Neuromed — Pozzilli, Isernia, Italy (RECRUITING)

Study contacts

• Principal investigator: Diego Centonze — IRCCS Neuromed, Pozzilli, Isernia Italy
• Study coordinator: Diego Centonze, MD

Conditions: Relapsing Multiple Sclerosis, ADA, Genetic polymorphism, Immune-reconstitution therapy, 2-CdA, single nucleotide polymorphisms, lymphopenia induced by 2-CdA treatment, ADA genetic variant rs244072