A controlled phase II clinical trial evaluating the safety and efficacy of myelin peptide-loaded tolDC as treatment for Multiple Sclerosis

Prior treatment

• Previous use of severe immunosuppressive or cytostatic treatment, including cyclophosphamide, mitoxantrone, bone marrow transplantation or (hematopoietic or mesenchymal) stem cell transplantation (at any time) prior to enrolment
• Drug or alcohol abuse
• Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease
• Previous treatment in the phase I clinical trial with tolDC
• Use of another investigational product in the past 6 months or longer depending on the mode of action
• Previous use of azathioprine or methotrexate in the past 3 months
• Previous use of other immunosuppressive agents washout is at least 3 months or longer depending on the mode of action and half-life
• Relapse / use of corticosteroids for any reason in the previous month

Other illness

• History of or actual signs of immunodeficiency or malignancies
• History of oncological diseases unless local basal cell carcinoma
• Hepatitis B or C, HIV serology, syphilis or tuberculosis
• Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol

Lab values

• Previous use of cladribine with last course within last 2 years or alemtuzumab with last course within last 4 years; lymphocyte counts should be above 800/mm3
• Use of interferon beta and glatiramer acetate in the 4 previous weeks; use of teriflunomide in the previous 4 weeks with accelerated elimination procedure; use of dimethyl/diroximel fumarate in the previous 4 weeks with normal lymphocyte counts (above 800/mm3)
• Treatment with fingolimod, siponimod, ponesimod, ozanimod, natalizumab, immunoglobulins or plasmapheresis in the past 3 months; teriflunomide in the previous 15 weeks without accelerated elimination; anti-CD20 monoclonal antibody (including ofatumumab, rituximab and ocrelizumab) within the past 6 months prior to the first administration and until confirmation of B cell count normalization; for S1P modulators lymphocyte counts should be above 800/mm3

Other

• Fertile patients, both men and women, who are not using an adequate method of contraception. If the patient is menopausal or sterile, it must be documented in the medical history
• Inability to undergo MRI assessments
• Splenectomy
• Participating in another interventional clinical trial, assessing an IMP, or having participated in one, in the last 6 months
• Pregnancy or planning pregnancy in the next 18 months and breast feeding;

• MS according to most recent Mc Donald’s diagnostic criteria
• Ability to comply with the protocol assessments
• Appropriate venous access
• Use of adequate contraceptive measures during the duration of the trial. Women and men of reproductive potential can only be included in the study following use of adequate contraceptive measures. Accepted methods of contraception include use of hormonal contraceptives (oral, intravaginal, intrauterine, or transdermal), intrauterine devices, sterilization or postmenopausal status, use of condoms with spermicide
• Age 18-60 years
• Expanded disability status scale (EDSS) of 0-6.0 inclusive
• Active MS (relapsing and progressive): 1 relapse in the past year and/or at least 1 enhancing lesion on brain MRI in the past year and/or at least 1 new or enlarging T2 lesion in comparison with a reference scan from maximum 1 year before
• MS patients on first-line treatment (control arm) or untreated patients (no wish to be treated with currently available disease-modifying treatments or presence of treatment- related side effects; intervention arms)
• No evidence of relapse in the month prior to start of screening and throughout the screening phase
• Normal total lymphocyte count
• Normal peripheral B cell count
• Able to sign informed consent