Relapsing Remitting Multiple SclerosisPhase 4ToFingo2NCT02325440
Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya
A Phase 4 study testing Fingolimod and Natalizumab in people with Relapsing Remitting Multiple Sclerosis, run by University Hospital Muenster at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Fingolimod and Natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2014to Apr 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- positive JC virus (JCV) antibody status
- adverse effects including hypersensitivity reactions
- presence of anti-natalizumab neutralizing antibodies
- any other valid medical reason
Who cannot join
- 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.
Show all 26Show fewer
- 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.
- Patients with certain cardiovascular conditions and/or findings in the screening ECG.
- Patients with certain lung diseases.
- Patients with certain hepatic conditions.
- Patients with a screening white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3.
- Patients with certain neurologic/psychiatric disorders:
- Patients unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-diethylenetriaminepentacetate (Gd-DTPA).
- Patients who have received an investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer.
- Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin laboratory.
- Women of child-bearing potential unless they are using effective contraception during the study and for 5 half-lives after stopping treatment. In case of use of oral contraception women should have been stable on the same medication for a minimum of 3 months before baseline.
- History of hypersensitivity to the study drugs or to drugs of similar chemical classes.
- Prior participation in a trial with fingolimod.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Universitaetsklinikum Muenster, Department of Neurology
Münster, 48149
Luisa Klotz, PD Dr. med., +49 251 83444 ext. 52, luisa.klotz@ukmuenster.de
Luisa Klotz, PD Dr. med.
About this study
Official title: A 32-week, Monocentric, Exploratory, Single Arm Study to Assess Immune Function and MRI Disease Activity in Patients With RRMS Transferred From Previous Treatment With Natalizumab to Gilenya® (Fingolimod)
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.
Read the detailed description
Patients are screened and must sign informed consent at visit 1. At the 2nd visit, all patients receive a baseline infusion of Natalizumab, which is followed by an 8 week washout Phase. After the washout Phase all patients receive fingolimod for 32 weeks.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Fingolimod, Natalizumab
- Keywords
- RRMS (relapsing remitting multiple sclerosis), Cluster of differentiation 49d (CD49d), immune function, disease activity
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FingolimodDrug
Also called FTY720, Gilenya
Fingolimod: 0.5 mg p.o. (o.i.d)
NatalizumabDrug
Also called Tysabri
Natalizumab: 300 mg i.v. (once at baseline);
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fingolimod; Drug: Natalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: weeks: 12, 32
Secondary outcomes (2)
MRI disease activity over time by GD+, T2w and DTI
Number of active (new or newly enlarging) lesions are assessed over time by MRI (changes in Gadolinium (GD+), T2w lesions and DTI (Diffusion Tensor Imaging))
Measured: weeks: 0, 8, 12, 16, 24, 32
MRI disease activity over time by T1w / FLAIR
Number of active (new or newly enlarging) lesions are assessed over time by MRI (T1w / FLAIR (Fluid Attenuated Inversion Recovery)
Measured: weeks: 0, 8, 12, 16, 24, 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study startMar 2014
- Primary completionApr 2016 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Luisa Klotz, PD. Dr. med., Principal investigator, Universitätsklinikum Muenster, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325440
- Sponsor's protocol ID
- UKM12_0037
- Other IDs
- 2013-004616-21, CFTY720D2415T
- Acronym
- ToFingo2
- Status last verified
- Dec 2014
- First submitted
- 4 Sep 2014
- Last updated
- 25 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30050529
Study at a glance
From the registry record, last updated by the sponsor on 25 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 32-week, Monocentric, Exploratory, Single Arm Study to Assess Immune Function and MRI Disease Activity in Patients With RRMS Transferred From Previous Treatment With Natalizumab to Gilenya® (Fingolimod)
- ClinicalTrials.gov ID
- NCT02325440
- Acronym / sponsor ID
- ToFingo2 / UKM12_0037
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- RRMS (relapsing remitting multiple sclerosis), Cluster of differentiation 49d (CD49d), immune function, disease activity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2014
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients are screened and must sign informed consent at visit 1. At the 2nd visit, all patients receive a baseline infusion of Natalizumab, which is followed by an 8 week washout Phase. After the washout Phase all patients receive fingolimod for 32 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Natalizumab - Washout - Fingolimod | Experimental | Drug: Fingolimod, Drug: NatalizumabOne 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (26 listed)
- 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:
- History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
- Uncontrolled diabetes mellitus (HbA1c >7%).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FingolimodAlso: FTY720, GilenyaFingolimod: 0.5 mg p.o. (o.i.d) | Drug | Natalizumab - Washout - Fingolimod |
| NatalizumabAlso: TysabriNatalizumab: 300 mg i.v. (once at baseline); | Drug | Natalizumab - Washout - Fingolimod |
Primary outcome
Temporal changes in the expression of CD49d
Time frame: weeks: 12, 16, 20, 24, 28, 32
First Co-Primary Objective; Flow-cytometric analysis of temporal changes in the expression of CD49d of PBMCs; unit of measure: mean fluorescence intensity (MFI)
Migratory capacity of immune cells
Time frame: weeks: 12, 32
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
2 secondary outcomes
MRI disease activity over time by GD+, T2w and DTI
Time frame: weeks: 0, 8, 12, 16, 24, 32
MRI disease activity over time by T1w / FLAIR
Time frame: weeks: 0, 8, 12, 16, 24, 32
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Dec 2014.
- Derived from this study: PubMed 30050529Lohmann 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.
Related trials for Relapsing Remitting Multiple Sclerosis
Active, not recruiting
Tai Chi Training for Persons With Multiple Sclerosis.
Multiple Sclerosis (MS) - Relapsing-remitting
RecruitingObservational study
REAL-MS: Observational Database Study of AHSCT and MS Therapies
Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting
RecruitingPhase 2
The HIt HArd and hiT Early in Multiple Sclerosis Trial
Relapsing-remitting Multiple Sclerosis
RecruitingPhase 3
Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS)
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis
Not yet recruitingPhase 2
A Study to Evaluate Pharmacokinetics, Safety, Tolerability, Immunogenicity and Pharmacodynamic Effects of Subcutaneous Ocrelizumab Administration in Children and Adolescents With Relapsing-remitting Multiple Sclerosis (RRMS)
Relapsing-remitting Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luisa Klotz, PD. Dr. med. principal investigator
Universitätsklinikum Muenster, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fingolimod and Natalizumab in people with Relapsing Remitting Multiple Sclerosis, run by University Hospital Muenster at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luisa Klotz, PD Dr. med. (+49 251 98029 ext. 00, luisa.klotz@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Temporal changes in the expression of CD49d (time frame: weeks: 12, 16, 20, 24, 28, 32). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02325440, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Dec 2014; AzTrials last refreshed its copy on 30 Oct 2026.