Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya

NCT02325440 | Unknown Phase 4

• 3 other identifiers: UKM12_00372013-004616-21CFTY720D2415T
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

A trial in patients with relapsing remitting multiple sclerosis (RRMS) Main objectives:

• To evaluate changes in the reconstitution of immune surveillance over time upon switching from natalizumab to fingolimod assessed by a change in the expression of CD49d.
• To evaluate changes in the migratory capacity of immune cells/peripheral blood mononuclear cells (PBMCs) upon switching from natalizumab to fingolimod in an in-vitro model of the blood-brain-barrier (BBB).
• To evaluate changes in paraclinical disease activity over time upon switching from natalizumab to fingolimod assessed by MRI (changes in Gd+, T2w lesions and DTI).
• To evaluate changes in T1w / FLAIR lesions upon switching from natalizumab to fingolimod.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

RRMS (relapsing remitting multiple sclerosis); Cluster of differentiation 49d (CD49d); immune function; disease activity

Outcome Measures

Primary Outcomes (2)

• Temporal changes in the expression of CD49d

  First Co-Primary Objective; Flow-cytometric analysis of temporal changes in the expression of CD49d of PBMCs; unit of measure: mean fluorescence intensity (MFI)

  weeks: 12, 16, 20, 24, 28, 32

• Migratory capacity of immune cells

  Second Co-Primary Objective; in-vitro model of the blood-brain-barrier (BBB) with subsequent flow-cytometric analysis and bead based quantification assessing temporal changes in the migratory capacity of immune cells; unit of measure: fluorescence intensity

  weeks: 12, 32

Secondary Outcomes (2)

• MRI disease activity over time by GD+, T2w and DTI

  weeks: 0, 8, 12, 16, 24, 32

• MRI disease activity over time by T1w / FLAIR

  weeks: 0, 8, 12, 16, 24, 32

Study Arms (1)

Natalizumab - Washout - Fingolimod

EXPERIMENTAL

One experimental arm: Patients receive one final dose of natalizumab 300mg followed by an 8-week washout Phase and subsequent 32-week treatment Phase with fingolimod 0.5mg o.i.d.

Drug: Fingolimod; Drug: Natalizumab

Interventions

Fingolimod DRUG

Fingolimod: 0.5 mg p.o. (o.i.d)

Also known as: FTY720, Gilenya

Natalizumab - Washout - Fingolimod

Natalizumab DRUG

Natalizumab: 300 mg i.v. (once at baseline);

Also known as: Tysabri

Natalizumab - Washout - Fingolimod

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male and female subjects aged 18-65 yrs.
• Subjects with RRMS, defined by 2010 rev. McDonald criteria.
• Patients with an (EDSS) score of 0-6.0 inclusive.
• Patients on treatment with natalizumab for ≥ 12 months prior to screening where treatment discontinuation is considered for any of the following reasons:
• treatment duration for more than 2 years
• positive JC virus (JCV) antibody status
• adverse effects including hypersensitivity reactions
• presence of anti-natalizumab neutralizing antibodies
• any other valid medical reason

You may not qualify if:

• Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
• Patients with Crohn´s disease or ulcerative colitis.
• Patients who have been treated with:
• systemic corticosteroids or immunoglobulins within 1 month prior to baseline.
• immunosuppressive medications such as azathioprine, cyclophosphamide or methotrexate within 3 months prior to baseline.
• monoclonal antibodies (excluding natalizumab) within 3 months prior to baseline.
• cladribine or mitoxantrone at any time.
• History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
• Uncontrolled diabetes mellitus (HbA1c \>7%).
• Diagnosis of macular edema during Screening Phase.
• Severe active infections, active chronic infection.
• Negative for varicella-zoster virus immunoglobulin G antibodies prior to baseline.
• Patients that received any live or live-attenuated vaccine (including varicella-zoster virus or measles) within 1 month prior to baseline.
• Patients who have received total lymphoid irradiation or bone marrow transplantation.
• Patients with any medically unstable condition, as assessed by the investigator.

Sponsors & Collaborators

• University Hospital Muenster: lead
• Novartis: collaborator

Study Sites (1)

Universitaetsklinikum Muenster, Department of Neurology

Münster, 48149, Germany

RECRUITING

Related Publications (1)

• Lohmann L, Janoschka C, Schulte-Mecklenbeck A, Klinsing S, Kirstein L, Hanning U, Wirth T, Schneider-Hohendorf T, Schwab N, Gross CC, Eveslage M, Meuth SG, Wiendl H, Klotz L. Immune Cell Profiling During Switching from Natalizumab to Fingolimod Reveals Differential Effects on Systemic Immune-Regulatory Networks and on Trafficking of Non-T Cell Populations into the Cerebrospinal Fluid-Results from the ToFingo Successor Study. Front Immunol. 2018 Jul 9;9:1560. doi: 10.3389/fimmu.2018.01560. eCollection 2018.

  PMID: 30050529 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Fingolimod Hydrochloride; Natalizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luisa Klotz, PD. Dr. med.

  Universitätsklinikum Muenster, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luisa Klotz, PD Dr. med.

CONTACT

+49 251 98029; luisa.klotz@ukmuenster.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: December 25, 2014
• Study Start: March 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 25, 2014

Record last verified: 2014-12

Locations

DE (1)