Trials

The following are a list of the current clinical trials we are recruiting patients for. If you have nay queries concerning this trials please contact Ceri Guarnieri in the Clinical Research Centre ( ceri.guarnieri@bartsandthelondon.nhs.uk ).

Study 1. An exploratory phase IIa study to evaluate the safety and immunological effects of intravenous interferonβ-1a (IFNβ-1a, Rebif® New Formulation) therapy in the induction of tolerance to IFNβ in MS patients with neutralising antibodies (NAbs) to subcutaneous IFNβ-1a (Rebif® or Avonex®)

Inclusion criteria

1. Confirmed diagnosis of MS according to the McDonald criteria. 
2. Current treatment with Rebif® (22 or 44) s.c. TIW or Avonex® i.m. once per week for at least 12 months 
3. At least one relapse in the last 12 months 
4. Two consecutive positive NAb titers of ³20NU at least 4 weeks apart. 
5. Age over 18 years and less than 65 years. 
6. Expanded Disability Status Scale (EDSS) score not to exceed 6.5. 
7. Women of childbearing potential and men must agree to practice adequate contraception methods.
8. Must give written informed consent and authorize the release and use of protected health information, as required by local law.
9. Able and willing to undergo blood sampling at regular intervals as defined by the protocol. 
10. Able to comply with study requirements. 

Exclusion criteria

1. Treatment with other immunosuppressive, immunomodulatory, or experimental treatments within the last 6 months of enrollment in the study, but excluding pulsed intravenous or oral steroids for treatment of MS relapse relapse or IFNβ. 
2. History of WHO grade 3 or 4 liver toxicity with IFNβ-1a 
3. Patients presenting a severe or unstable disorder: poorly controlled diabetes, arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (>2.5 times ULN) and abnormal complete blood count (in particular leukopenia and thrombocytopenia < 1.5 LLN), or any medical condition which, in the opinion of the chief investigator, would pose additional risk in administering IFNβ-1 to the patient. 
4. Presence of chronic or recurrent infection or human immunodeficiency virus. 
5. Exposure to any other investigational drug within 30 days of enrollment in the study. 
6. History of malignancy unless an exception is granted by the Chief Investigator. 
7. History of drug or alcohol abuse within 6 months prior to enrollment into the study. 
8. Pregnancy or breast feeding. 
9. Left Ventricular Ejection Fraction (LVEF) < 50% on echocardiogram or an abnormal 12-lead ECG

Study 2: OCRELIZUMAB IN PPMS WA25046

INCLUSION CRITERIA

Primary Progressive MS

18-50 yrs

EDSS 3.0 – 6.5

2.0 or more FSS pyramidal (due to lower extremity findings)

Disease duration from symptom onset:

• Less than 15 yrs in pts with EDSS of  ≥ 5.0 at screening
• Less than 10 yrs in pts with EDSS of  ≤ 5.0 at screening

Documented history or presence at screening of at least one of the following lab findings in CSF (Can be conducted at screening)

• Elevated IgG index
• One or more IgG oligoclonal bands

3 month washout for DMD’s

6 month washout for investigational products

STUDY SCHEDULE

5x IV infusion treatment cycles

1^st cycle 1x IV infusion Day1 and Day 15

Subsequent IV infusions given every 24 weeks

Open label treatment after 120 weeks (IV infusion every 24 weeks)

Study duration 3-5.5 yrs

4 x MRI’s

Study 3. DECIDE BIOGEN 205-MS-301 DACLIZUMAB V INTERFERON β-1a

INCLUSION CRITERIA

18 – 55 yrs old

Relapsing Remitting MS

EDSS 0-5 (Able to walk 200m unaided)

2 relapses in last 3 yrs with I occuring in 12months prior to randomisation

OR

1 relapse and 1 or more new lesions (Gd enhancing and/or T2 intense lesion) in previous 2 yrs with at least one of these events in the 12 months prior to randomisation. (MRI lesion must be distinct from one associated with relapse)

NOTE

Current or prior use of approved IFNβ for MS, including Avonex allowed. No washout required prior to randomisation but IFNβ treatment to be discontinued prior to randomisation.

STUDY SCHEDULE

3yr study

Visits every 4 weeks

Duration of visits varies between 1-3hrs

5x injections per month (4x self administered 1x in clinic)

3 MRI’s

Study 4: A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With SPMS (ASCEND in SPMS)

Major Inclusion Criteria:

1. Age 18 to 58 years 
2. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. 
3. Be between the ages of 18 and 58, inclusive, at the time of informed consent. 
4. SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by MS relapses for at least 2 years. 
5. EDSS score of 3.0 to 6.5, inclusive. 
6. MS Severity Score (MSSS) of 4 or higher. 
7. Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide. 

Major Exclusion Criteria:

1. RRMS or primary progressive MS as defined by the revised McDonald Committee criteria. 
2. Clinical relapse (within 3 months) prior to randomization. 
3. T25FW test of >30 seconds during the screening. 
4. Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils. 
5. Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment. 
6. Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed). 
7. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study. 
8. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured). 
9. Known history of or positive test result for Human Immunodeficiency Virus (HIV). 
10. Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). 
11. History of transplantation or any anti-rejection therapy. 
12. Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening. 
13. History of PML or other opportunistic infections. 
14. Treatment History 
15. Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation. 
16. Any prior treatment with natalizumab. 
17. Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization. 
18. Treatment with IV or oral corticosteroids, intravenous immunoglobulin (IVIg), or plasmapheresis for treatment of MS within the 3 months prior to randomization. 
19. Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization. 
20. Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.