A Trial of Tocilizumab in ALS Subjects
Condition: ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig's Disease; Motor Neuron Disease
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This research study is being done to find out if tocilizumab, also known as Actemra™, can
      help with Amyotrophic Lateral Sclerosis (ALS). The investigators also want to find out if
      tocilizumab is safe to take without causing too many side effects.

      Currently ALS has no cure and 2 modestly effective treatment to slow the progression of the
      disease. Although not the initial cause of ALS, the immune system plays a role in the death
      of motor neurons. The immune cells that participate in this process are stimulated by a
      substance called interleukin-6 (IL-6) whose effect is blocked by tocilizumab and thus, may
      slow the death of motor neurons and slow the disease.
    

Detailed description: 
      This is a multicenter, randomized, double-blind, placebo-controlled 16-week study evaluating
      the safety and tolerability of tocilizumab in subjects with ALS.

      The primary objective of the study is to determine the safety and tolerability of intravenous
      administration of 8 mg/kg of tocilizumab every 4 weeks vs. matched intravenous placebo
      administered every 4 weeks over an 8 week period.

      The secondary objectives of the study are to describe the expression of pro-inflammatory
      genes in Peripheral Blood Mononuclear Cells (PBMCs) of sporadic ALS patients, to assess the
      ability of tocilizumab to reduce the expression of pro-inflammatory genes in PBMCs and
      pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with sporadic ALS and
      to assess the CSF penetration of tocilizumab. Mean peripheral benzodiazepine receptor 28
      (PBR28) uptake will be measured in the motor cortices as regions of interest (ROIs), and will
      be compared between pre- and post-dose, for Massachusetts General Hospital (MGH) subjects.

      Approximately 5 Northeast ALS Consortium (NEALS) Centers in the US will participate in the
      study. Twenty-four subjects will be randomized in the study.

      This study will be conducted in subjects who meet the El Escorial criteria of possible,
      laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At
      screening, eligible subjects must be at least 18 years old, must have a slow vital capacity
      (SVC) ≥ 40% of predicted capacity for age, height and gender (and in the opinion of the
      investigator is able to comply with and complete the trial), and must provide written
      informed consent prior to screening. Subjects on a stable dose of riluzole and those not
      taking riluzole, and women of child-bearing age at screening are eligible for inclusion as
      long as they meet specific protocol requirements. Detailed criteria are described in the body
      of the protocol.

      Subjects participating in the magnetic resonance imaging - positron emission tomography
      (MRI-PET) portion of the study (MGH only) must meet the following additional criteria.High or
      mixed affinity to bind translocator protein (TSPO) (Ala/Ala or Ala/Thr,) Upper Motor Neuron
      Burden (UMNB) Scale Score ≥25 (out of 45) at the Screening Visit.

      and have the ability to safely undergo MRI-PET scans based on the opinion of the site
      investigator.

      Subjects will be randomly assigned in a 2:1 ratio to intravenous tocilizumab 8 mg/kg or
      matching placebo every 4 weeks over an 8 week period.

      This research study protocol allows the subject to receive up to 3 infusions of Tocilizumab.
      Even if the treatment is shown to be of benefit, additional infusions of Tocilizumab beyond
      that allowed in the protocol cannot be given to the subject while she/he is participating in
      this study.

      Subjects will remain on randomized, placebo-controlled, double-blind treatment until the Week
      8 visit. Each randomized subject will also have a Week 12 Follow-up visit and Week 16
      End-of-Study visit to assess for adverse events (AEs), changes in concomitant medications, to
      administer the ALS Functional Rating Scale (ALSFRS-R) and selected study procedures.
    

Intervention name(s): Tocilizumab; Placebo
Intervention type(s): Drug; Other
Intervention description(s): IV Infusion; IV Infusion
Other intervention name(s): Actemra; Saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ALS; tocilizumab; biomarker