Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy

NCT04640818 | Unknown

• 1 other identifier: EOCNSIMS.2001
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. No data have been published on the sequential use of anti CD20 therapies and cladribine, that is thought to act as an immune reconstitution agent. his study aims at investigating IgG and IgM serum concentration changes at 6 and 12 months after switching to cladribine in patients previously treated with anti CD20 therapies (ie, ocrelizumab ≥1.8 gr or rituximab 3.0 gr) for ≥18 months, as compared to continued anti CD20 therapies.

Conditions

Multiple Sclerosis

Keywords

anti CD20 therapy; cladribine

Outcome Measures

Primary Outcomes (4)

• Changes in IgG serum concentrations in Cald-Group

  Standard laboratory test

  6 months

• Changes in IgM serum concentrations in Cald-Group

  Standard laboratory test

  6 months

• Changes in IgG serum concentrations in Clad-Group

  Standard laboratory test

  12 months

• Changes in IgM serum concentrations in Clad-Group

  Standard laboratory test

  12 months

Secondary Outcomes (11)

• Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies

  6 months

• Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies

  6 months

• Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies

  12 months

• Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies

  12 months

• Proportion of patients reaching NEDA -3

  12 months

Other Outcomes (12)

• Frequency of infections

  6 months

• Frequency of infections

  12 months

• Intensity of infections

  6 months

Study Arms (2)

CLAD-GROUP

Patients with cladribine therapy

Drug: Cladribine Oral Tablet

CD20-GROUP

Patients with anti CD20 therapy (ocrelizumab or rituximab)

Drug: Rituximab; Drug: Ocrelizumab

Interventions

Cladribine Oral Tablet DRUG

Treatment according to the label and medical prescription

Also known as: Mavenclade

CLAD-GROUP

Rituximab DRUG

Treatment according to the label and medical prescription

Also known as: Mabthera, Rixathon

CD20-GROUP

Ocrelizumab DRUG

Treatment according to the label and medical prescription

Also known as: Ocrevus

CD20-GROUP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with relapsing multiple sclerosis

You may qualify if:

• Relapsing MS according to Lublin;
• Treatment with ocrelizumab or rituximab for ≥18 months and having received 1.8 / 3.0 gr, respectively;
• CLAD\_GROUP: Planning to switch to cladribine because of concerns about increased risks of infections related to hypogammaglobulinemia developing during long term anti CD20 therapies or a documented decrease of ≥10% IgG and/or IgM compared to pre- anti CD20 therapy;
• or CD20\_GROUP: no need to stop CD20 therapy due decrease of ≥10% IgG and/or IgM, or increased risk of infections related to hypogammaglobulinemia or other reasons, continued anti CD20 therapies clinically indicated;
• EDSS ≤7.0;
• Age \>18 years.

You may not qualify if:

• Non relapsing MS;
• Pregnancy - breastfeeding;
• Contraindications to perform MRI;
• Contraindication to receive cladribine or to continue anti CD therapies

Sponsors & Collaborators

• Claudio Gobbi: lead
• Merck AG Switzerland: collaborator

Study Sites (1)

Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano

Lugano, Canton Ticino, 6903, Switzerland

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine; Rituximab; ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Claudio Gobbi, MD

  Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head Physician

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 23, 2020
• Study Start: December 17, 2020
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: March 23, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)