Investigating Mechanism of Action of DAC HYP in the Treatment of High-Inflammatory Multiple Sclerosis (MS)
Condition: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 1

Summary: 
      Objective:

      The primary goal of this study is to investigate the mechanism of action (MOA) of
      CD25-blocking therapies in high inflammatory multiple sclerosis (HI-MS). The secondary goal
      of this study is to assess long-term safety and efficacy of CD25-blocking therapies in HI-MS.

      Study population:

      Two cohorts of patients will be enrolled:

        -  Long-term daclizumab therapy cohort: Up to 15 daclizumab-treated patients with
           relapsing-remitting (RR-MS) or secondary-progressive MS (SP-MS) previously classified as
           HI-MS based on MRI/clinical criteria, who have been treated with IV daclizumab for a
           minimum of 1 year and responded to this therapy with significant (>70%) decrease in
           contrast-enhancing lesions (CEL) or stabilization/improvement of disease activity (>60%
           decrease in MS relapses and stable or improved EDSS disability score).

        -  New treatment cohort: Up to 15 HI-MS patients (RR- or SP-MS) with inadequate therapeutic
           response to first-line, FDA-approved immunomodulatory therapies for MS or who cannot,
           for any reason, be treated with first-line, FDA-approved immunomodulatory therapies for
           MS.

      Design:

      This is an open label, Phase I trial of 150 mg of daclizumab high yield process (DAC HYP)
      administered subcutaneously (SC) every 4 weeks for a total of 3 years.

      Outcome measures:

      Because the main goal of this study is to investigate the MOA of CD25-blocking therapies in
      MS, the primary outcomes are mechanistic immunological studies performed on clinical samples
      (peripheral blood mononuclear cells (PBMC), cerebrospinal fluid (CSF) cells and skin
      biopsies) derived from DAC HYP-treated patients. The secondary outcome measure is long-term
      safety and tolerability of subcutaneous DAC HYP in HI-MS patients.
    

Detailed description: 
      Objective:

      The primary goal of this study is to investigate the mechanism of action (MOA) of
      CD25-blocking therapies in high inflammatory multiple sclerosis (HI-MS). The secondary goal
      of this study is to assess long-term safety and efficacy of CD25-blocking therapies in HI-MS.

      Study population:

      We will enroll up to 70 patients. We expect to screen up to 40 HI-MS participants to yield 31
      patients that will receive study drug. Two cohorts of patients will be enrolled for the
      treatment part of the protocol: A. Long-term daclizumab therapy cohort: 16 daclizumab-treated
      patients with relapsing-remitting (RR-MS) or secondary-progressive MS (SP-MS) previously
      classified as HI-MS based on MRI/clinical criteria, who have been treated with IV daclizumab
      for a minimum of 1 year and responded to this therapy with significant (>70%) decrease in
      contrast-enhancing lesions (CEL) or stabilization/improvement of disease activity (>60%
      decrease in MS relapses and stable or improved EDSS disability score). B. New treatment
      cohort: 15 HI-MS patients (RR- or SP-MS) with inadequate therapeutic response to first-line,
      FDA-approved immunomodulatory therapies for MS or who choose not to, for any reason, be
      treated with first-line, FDAapproved immunomodulatory therapies for MS. Up to 30 subjects
      with inflammatory MS will be screened to yield 20 controls for immunization and skin biopsy
      studies (Cohort C: MS controls).

      Design:

      This is an open label, Phase I trial of 150 mg of daclizumab high yield process (DAC HYP)
      administered subcutaneously (SC) every 4 weeks for a total of 3 years.

      Outcome measures:

      Because the main goal of this study is to investigate the MOA of CD25-blocking therapies in
      MS, the primary outcomes are mechanistic immunological studies performed on clinical samples
      (peripheral blood mononuclear cells (PBMC), cerebrospinal fluid (CSF) cells and skin
      biopsies) derived from DAC HYP-treated patients. The secondary outcome measure is long-term
      safety and tolerability of subcutaneous DAC HYP in HI-MS patients.
    

Intervention name(s): DAC-HYP
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Daclizumab