A Trial of Tocilizumab in ALS Subjects (TCZALS-001)
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|ClinicalTrials.gov Identifier: NCT02469896|
Recruitment Status : Completed
First Posted : June 12, 2015
Last Update Posted : July 26, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|ALS Amyotrophic Lateral Sclerosis Lou Gehrig's Disease Motor Neuron Disease||Drug: Tocilizumab Other: Placebo||Phase 2|
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 PBR28 uptake will be measured in the motor cortices as regions of interest (ROIs), and will be compared between pre- and post-dose, for 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 MR-PET portion of the study (MGH only) must meet the following additional criteria.High or mixed affinity to bind TSPO protein (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 PET/MRI 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 ALSFRS-R and selected study procedures.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2 Randomized, Placebo Controlled Trial of Tocilizumab in ALS Subjects|
|Study Start Date :||November 2015|
|Actual Primary Completion Date :||July 11, 2018|
|Actual Study Completion Date :||July 11, 2018|
Placebo Comparator: Placebo
8 subjects will receive matching IV placebo every 4 weeks for 3 months.
Other Name: Saline
Active Comparator: Active drug
16 subjects will receive 8mg/kg of IV tocilizumab every 4 weeks for 3 months.
Other Name: Actemra
- Safety and Tolerability [ Time Frame: 16 weeks ]Safety will be assessed by the occurrence of severe adverse events (SAEs), overall rates of adverse events (AEs), clinically significant abnormal laboratory tests, and changes in vital signs. Tolerability will be assessed by on the proportion of participants remaining on study drug through all 3 doses and remaining on study and free from possibly drug-related and dose-limiting SAEs to the end of follow-up.
- Efficacy SVC [ Time Frame: 16 weeks ]Efficacy will be assessed by the change in the rate of change of SVC.
- Efficacy ALSFRS-R [ Time Frame: 16 weeks ]Efficacy will be assessed by the change in the rate of change of ALSFRS-R.
- Efficacy HHD [ Time Frame: 16 weeks ]Efficacy will be assessed by the change in the rate of change of HHD.
- Target engagement ( change in PBMC pro-inflammatory gene expression) [ Time Frame: 16 weeks ]Target engagement will be assessed by comparing the gene expression profiles of ALS patient receiving drug versus placebo.
- Target engagement (change in CSF sIL-6 receptor concentrations) [ Time Frame: 16 weeks ]Target engagement will be assessed by changes in CSF sIL-6 receptor concentrations.
- Target engagement (changes in cytokine levels in the serum and CSF) [ Time Frame: 16 weeks ]Target engagement will be assessed by changes in cytokine levels in the serum
- PBR28 PET [ Time Frame: 8 weeks ]Measure the effects of tocilizumab on reducing glial activation measured by PBR28 PET in a subset of trial participants.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469896
|United States, Arizona|
|Barrow Neurological Institute|
|Phoenix, Arizona, United States, 85013|
|United States, Kansas|
|University of Kansas Medical Center|
|Kansas City, Kansas, United States, 66160|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, North Carolina|
|Wake Forest University School of Medicine|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Pennsylvania|
|Penn State College of Medicine Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||Shafeeq Ladha, MD||Barrow Neurological Institute|