OBJECTIVES: I. Evaluate the safety and immunogenicity of single and multiple doses of M-T412, a chimeric murine-human anti-CD4 monoclonal antibody, in patients with multiple sclerosis. II. Evaluate the pharmacokinetics of M-T412. III. Obtain preliminary data on the clinical response to M-T412.

Condition	Treatment or Intervention	Phase
Multiple Sclerosis	Drug: monoclonal antibody M-T412	Phase I

Further Study Details: 

Expected Total Enrollment:  25

PROTOCOL OUTLINE: This is an open label, dose escalating study. Escalating doses of M-T412 are administered to cohorts of 5 patients each receiving a single dose intravenously over 2 hours. Patients who complete the single dose assessment of M-T412 may receive up to 3 additional single doses of M-T412 IV over 2 hours, with each repeated dose given at least 1 month apart. Then, patients receive one dose level of M-T412 IV over 2 hours at 3 month intervals over a period of 12 months for a total of 5 doses. Once recovery of CD4 cells is obtained, the next scheduled infusion of M-T412 begins. Patients are omitted from study if CD4 cells remain attenuated following 2 scheduled infusion sessions. Patients are followed at 3, 6, 12, and 24 months after the first infusion.

Ages Eligible for Study:  21 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of chronic, advanced, progressive multiple sclerosis (MS)

--Prior/Concurrent Therapy--

• Biologic therapy: No sensitivity to murine proteins No prior treatment at any time with anti-CD4 antibodies, other murine antibodies, or other anti-T cell antibodies (e.g., xenologous or human) At least 4 weeks since use of other biological agents
• Chemotherapy: No concomitant chemotherapy At least 3 months since prior chemotherapy
• Endocrine therapy: No concomitant steroidal therapy At least 3 months since prior steroidal therapy
• Radiotherapy: No total lymphoid irradiation prior to study No concomitant radiotherapy At least 3 months since prior radiotherapy
• Other: No use of investigational drugs within 30 days prior to study

--Patient Characteristics--

• Age: 21 to 75
• Hematopoietic: Hemoglobin at least 10 g/dL WBC at least 4000/mm3 Granulocyte count at least 1500/mm3 Platelet count at least 100,000/mm3 CD4+ lymphocyte count at least 300 cells/mm3
• Other: Not pregnant or lactating Effective contraception required of fertile patients for 3 months prior to and during study No substance abuse (e.g., drug or alcohol) Not HIV positive No AIDS-Related Complex (ARC) No serum antibodies to HIV Negative serum antibody test for HIV within 1 month prior to study No underlying medical or psychiatric condition

Study chairs or principal investigators

Lawrence Steinman,  Study Chair,  Stanford University   

Study ID Numbers:  199/12050; SUMC-C0128T03
Record last reviewed:  December 2001
Last Updated:  October 13, 2004
Record first received:  February 24, 2000
ClinicalTrials.gov Identifier:  NCT00004816
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08