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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT02469896
Date of registration: 03/06/2015
Prospective Registration: Yes
Primary sponsor: Barrow Neurological Institute
Public title: A Trial of Tocilizumab in ALS Subjects TCZALS-001
Scientific title: A Phase 2 Randomized, Placebo Controlled Trial of Tocilizumab in ALS Subjects
Date of first enrolment: November 2015
Target sample size: 22
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT02469896
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).  
Phase:  Phase 2
Countries of recruitment
United States
Contacts
Name:     Shafeeq Ladha, MD
Address: 
Telephone:
Email:
Affiliation:  Barrow Neurological Institute
Key inclusion & exclusion criteria

Inclusion Criteria:

- Participants with ALS (El Escorial criteria: possible, laboratory-supported probable,
probable or definite)

- Capable of providing informed consent and complying with trial procedures.

- High inflammatory profile of PBMC gene expression

- Upright SVC =40% of predicted value for gender, height and age at Screening and in the
opinion of the investigator is able to comply with and complete the trial.

- Women must not be able to become pregnant for the duration of the study.

- Negative tuberculosis blood or skin test at Screening

- Not taking riluzole, or on a stable dosage for at least 30 days prior to Screening.

- Subjects medically able to undergo lumbar puncture (LP)

- Subjects must agree not to take live attenuated vaccines 30 days before Screening,
throughout the duration of the trial and for 60 days following the subject's last dose
of study drug

- Geographic accessibility to the study site

Additional MRI-PET Inclusion Criteria (MGH only):

- High or mixed affinity to bind TSPO protein (Ala/Ala or Ala/Thr) (see section 7.1)

- Upper Motor Neuron Burden (UMNB) Scale Score =25 (out of 45) at the Screening Visit.

- Able to safely undergo MRI-PET scans based on the opinion of the site investigator.

Exclusion Criteria:

- Prior use of Tocilizumab, cell-depleting therapies, alkylating agents, total lymphoid
irradiation

- Stem cell therapies

- Dependence on mechanical ventilation as defined as being unable to lay supine without
it, unable to sleep without it, or continuous daytime use

- Presence of tracheostomy at Screening

- Exposure to any anti-inflammatory agent currently under investigation for the
treatment of patients with ALS (off label use or investigational) within 30 days prior
to the Screening Visit (examples include NP001 and Lunasin). Medications that do not
have an anti-inflammatory mechanism, such as mexiletine or retigabine are allowed if
on stable dose for 30 days prior to Screening visit

- Treatment with a prohibited medication within 30 days of the Screening Visit

- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6
months of Screening

- Presence of diaphragm pacing system at Screening.

- Primary or secondary immunodeficiency (history of or currently active) unless related
to primary disease under investigation

- History of or active diverticulitis, diverticulosis requiring antibiotic treatment,
peptic ulcer disease, or gastrointestinal (GI) tract perforation, or chronic
ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other
symptomatic lower GI conditions that might predispose to perforations

- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other opportunistic infections.

- History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies

- Presence of any of the following clinical conditions: bleeding diathesis, or any other
clinical condition that would, in the opinion of the investigator, place the patient
at increased risk during LP. Drug abuse or alcoholism within the past 12 months.
Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active
infectious disease, including current or prior malignancy. Rheumatic autoimmune
disease, mixed connective tissue disease, scleroderma, polymyositis, or significant
systemic involvement secondary to rheumatoid arthritis. Evidence of active malignant
disease, malignancies diagnosed within the previous 5 years, or breast cancer
diagnosed within the previous 5 years. Human immunodeficiency virus infection or other
immunodeficient state.Uncontrolled hypertension defined as systolic blood pressure >
170 or diastolic blood pressure > 110. Unstable psychiatric illness defined as
psychosis or untreated major depression within 90 days of the Screening Visit

- Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening

- Screening alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total
bilirubin > than 1.5 times the upper limit of normal (ULN), serum creatinine > 1.6
mg/dL in female patients and > 1.9 mg/dL in male patients (patients with serum
creatinine values exceeding limits may be eligible for the study if their estimated
glomerular filtration rate (GFR) are >30), hemoglobin < 85 g/L, white blood cells <
3.0 x 109/L, absolute neutrophil count of <2000/mm3, absolute lymphocyte count < 0.5 x
109/L, platelet concentration of <100,000/mm3, positive Hepatitis B surface antigen
(HBsAg)

- Pregnant women or women currently breastfeeding

- No history of chicken pox infection or no history of varicella zoster vaccination

- Any reason in the opinion of the investigator that the patient may not be able to
comply with study procedures, complete the study or is unsuitable for
immunosuppressive therapy.

Additional MR-PET Exclusion Criteria (MGH only):

- Any contraindication to undergo MRI studies such as

- History of a cardiac pacemaker or pacemaker wires

- Metallic particles in the body

- Vascular clips in the head

- Prosthetic heart valves

- Claustrophobia

- Radiation exposure that exceeds the site's current guidelines

- Current use of tobacco products including cigarettes, e-cigarettes, cigars, snuff and
chewing tobacco, or nicotine replacement products such as gum, or patch

- Taking any other anti-inflammatory or immune modulating medications except for over
the counter NSAIDs

- Unwilling or unable to discontinue benzodiazepine usage (other than Lorazepam,
Clonazepam, or Zolpidem) for one day prior to scanning



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All
Health Condition(s) or Problem(s) studied
Amyotrophic Lateral Sclerosis
Lou Gehrig's Disease
ALS
Motor Neuron Disease
Intervention(s)
Drug: Tocilizumab
Other: Placebo
Primary Outcome(s)
Number of Patients Tolerant to Study Drug [Time Frame: 16 weeks]
Rates of All-cause Mortality [Time Frame: 16 weeks]
Secondary Outcome(s)
Changes in Cytokine Levels in the Plasma [Time Frame: 16 weeks]
Change in Peripheral Blood Mononuclear Cell (PBMC) Gene Expression [Time Frame: 16 weeks]
Rate of Decline ALS Functional Rating Scale Revised (ALSFRS-R) [Time Frame: 16 weeks]
Peripheral Benzodiazepine Receptor 28 (PBR28) Positron Emission Tomography (PET) [Time Frame: 8 weeks]
Rate of Decline Handheld Dynamometry (HHD) [Time Frame: 16 weeks]
Rate of Decline in Slow Vital Capacity (SVC) [Time Frame: 16 weeks]
Change in CSF Soluble Interleukin-6 (sIL-6) Receptor Concentrations [Time Frame: 8 weeks]
Change in Mean Concentration Cytokines in the Cerebrospinal Fluid (CSF) [Time Frame: 8 weeks]
Secondary ID(s)
2015TCZALS-001
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
ALS Association
Barrow Neurological Foundation
Genentech, Inc.
Massachusetts General Hospital
Ethics review
Results
Results available: Yes
Date Posted: 18/12/2019
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT02469896
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