Cladribine Tablets After Treatment With Natalizumab (CLADRINA)

NCT04178005 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: STU 2019-1618
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to generate hypotheses regarding the safety, efficacy, and immunological impact of cladribine tablets after treatment with natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (active SPMS).

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Absolute and percent change of T cells, B cells, DC subset and NfL levels in blood.

  The absolute and percent change from baseline will be presented for each time point for CD3+ T lymphocytes, CD19+ B lymphocytes, CD11c+ DC subsets, NfL levels in blood, with a two-sided 95% CI and p value. As these data are not expected to be normally distributed, the nonparametric Wilcoxon signed rank test will be used to compare each biomarker at baseline and during treatment. Spearman rank correlations will be used to examine the relationship between biomarkers and clinical/safety endpoints.

  24 months

Secondary Outcomes (1)

• Annualized Relapse Rate (ARR)

  12 months

Other Outcomes (2)

• The Expanded Disability Status Scale : Neurological disability outcome

  24 months

• Magnetic Resonance imaging (MRI) outcomes

  24 months

Study Arms (1)

Cladribine

OTHER

All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI. Each treatment course is divided into 2 treatment cycles: * Administration of first treatment course (year 1 treatment): * First cycle: Starts on Day 1 of the study * Second cycle: Administered 23 to 27 days after the last dose of first cycle. * Administration of second treatment course (year 2 treatment): * First cycle: Administered at least 43 weeks after the last dose of year 1 treatment * Second cycle: Administered 23 to 27 days after the last dose of first cycle of year 2 treatment. The cycle dosage will be administered as 1 or 2 cladribine 10 mg tablets daily over 4 or 5 consecutive days.

Drug: Cladribine

Interventions

Cladribine DRUG

All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI

Also known as: Mavenclad

Cladribine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60 years, inclusive.
• Diagnosis of relapsing forms of MS, to include RRMS and active SPMS, diagnosed with McDonald Criteria 2005, 2010, and/or 2017 (1-3)
• EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
• Has had a minimum of 12 months of continuous natalizumab therapy (300 mg/d), including patients receiving extended interval dosing of natalizumab (e.g., less frequently than every-4-week infusion).
• Negative history for any relapses at least 28 days prior to enrollment.
• Weighing between 40 kilograms or more.
• Female subjects of childbearing potential must use effective methods of contraception to prevent pregnancy for 4 weeks before initiation of cladribine tablets and must agree to continue to practice adequate contraception for at least 6 months after the last dose. Women using systemically acting hormonal contraceptives should add a barrier method during cladribine treatment and for at least 4 weeks after the last dose in each treatment year.
• Female subjects must not be pregnant; female subjects must not be lactating or breast-feeding at least 10 days after the last dose.
• Male subjects must be willing to use a condom during dosing and for six months after the last dose. Alternatively, their female partner must use another form of contraception (such as an intra-uterine device \[IUD\], barrier method with spermicide, or hormonal contraceptive \[e.g., implant, injectable, patch or oral\]) during dosing and for six months after last dose.
• Understands and is capable of following through with study protocol requirements and assessments.
• Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA).

You may not qualify if:

• Natalizumab failure based on clinician's discretion.
• Not active progressive MS (4).
• A diagnosis of PML or any suspicion of PML.
• A diagnosis of Clinically Isolated Syndrome
• Known hypersensitivity to cladribine.
• Any prior exposure to cladribine.
• Lymphocyte count not within normal limits of the local, hospital laboratory.
• Previous or current exposure to mitoxantrone, azathioprine, methotrexate, cyclophosphamide, myelosuppressive treatments, total lymphoid irradiation.
• Receiving oral or systemic corticosteroid treatments within the 28 days prior to enrollment.
• Receiving cytokine base treatment, Intra Venous Immuno Globulin (IVIG) or Plasma pheresis, 3 months prior to enrollment in the study.
• Having platelet count or neutrophil count below the lower limit of the normal range within the 28 days prior to enrollment in the study.
• Positive for HIV, or positive hepatitis C antibody test or hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM.
• History of tuberculosis (TB), presence of active tuberculosis, or latent tuberculosis as detected by local standard of practice like imaging (e.g., chest X-ray, chest CT scan, MRI) and/or positive QuantiFERON-TB Gold test and/or skin test and/or clinical examination or has had latent TB disease at any time in the past.
• Immunocompromised subjects, including subjects currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids.
• Active malignancy or history of malignancy.

Sponsors & Collaborators

• EMD Serono: collaborator
• University of Texas Southwestern Medical Center: lead

Study Sites (2)

College Park Family Care Center Physicians Group

Overland Park, Kansas, 66212, United States

Location

UT Southwestern Medical center

Dallas, Texas, 75390, United States

Location

Related Publications (39)

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MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine

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

Study Officials

• Olaf Stuve, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: November 26, 2019
• Study Start: February 19, 2020
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)