Clinical trial: IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS) (NCT03474263)

Eligibility criteria:
Inclusion Criteria:

          1. Capable of providing informed consent and informed consent form signed prior to
             initiation of any study-specific procedures.

          2. Familial or sporadic ALS defined as clinically possible, probable, or definite by El
             Escorial Criteria.

          3. Rapidly progressive ALS defined by the Revised ALS Functional Rating Scale (ALSFRS-R)
             slope ≥1 (48 minus ALSFRS-R score at screening / disease duration in months ≥ 1).

          4. Upper Motor Neuron Burden Score of ≥ 25 (out of 45) at screening

          5. First symptoms of ALS within 3 years of the screening visit

          6. Age between 18 and 80 years at the time of the screening visit.

          7. Not taking riluzole or edaravone or on a stable dose of riluzole or edaravone for at
             least 3 months prior to screening visit.

          8. Adequate bone marrow reserve, renal and liver function:

               1. absolute neutrophil count ≥ 1500/µL

               2. lymphocyte count < 6000/µL

               3. platelet count ≥ 150,000/µL

               4. hemoglobin ≥ 11 g/dL

               5. creatinine clearance ≥ 60 mL/min

               6. alanine transaminase (ALT) and/or aspartate transaminase (AST) ≤ 3x upper limits
                  of normal (ULN)

               7. total bilirubin ≤ 1.5x ULN

               8. serum albumin ≥ 2.8 g/dL

          9. Females of childbearing potential should be using and committed to continue using one
             of the following acceptable birth control methods:

               1. Sexual abstinence (inactivity) for 1 month prior to screening through study
                  completion; or

               2. Intrauterine device (IUD) in place for at least 3 months prior to study through
                  study completion; or

               3. Stable hormonal contraception for at least 3 months prior to study through study
                  completion; or

               4. Surgical sterilization (vasectomy) of male partner at least 6 months prior to
                  study.

         10. To be considered of non-childbearing potential, females should be surgically
             sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least
             2 months prior to study) or be post-menopausal and at least 3 years since last menses.

         11. Males with female partners of childbearing potential must use contraception through
             study completion.

         12. Ability to safely lie flat for 90 min for magnetic resonance-positron emission
             tomography (MR-PET) procedures in the opinion of the Investigator.

         13. Patients must also have a genotype associated with a high or mixed affinity
             translocator protein (TSPO) (Ala/Ala or Ala/Thr) and ability to safely undergo MR-PET
             scans based on the opinion of the Investigator.

        Exclusion Criteria:

          1. Dependence on invasive or non-invasive ventilation, defined as being unable to lay
             supine without it, unable to sleep without it, or continuous daytime use; presence of
             tracheostomy at screening; or presence of diaphragm pacing system at screening.

          2. Exposure to any experimental treatment for ALS within the last 30 days or five
             half-lives, whichever is longer.

          3. Treatment within 12 months with immunomodulator or immunosuppressant agent (including
             but not limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β-1a,
             rituximab, alemtuzumab, azathioprine, etanercept, infliximab, adalimumab,
             certolizumab, golimumab, anakinra, rilonacept, secukinumab, tocilizumab, mycophenolate
             mofetil, methotrexate, cell-depleting agents, total lymphoid irradiation, dimethyl
             fumarate). Treatment with intravenous immunoglobulin (IVIG) within 2 months.
             Non-steroidal anti-inflammatory drugs (NSAIDs) are acceptable.

          4. Exposure at any time to any cell or gene therapies under investigation for the
             treatment of ALS.

          5. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
             or other opportunistic infections; or major episode of infection requiring
             hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks.

          6. Live-attenuated vaccines within 30 days before dosing. Subjects must agree to forego
             live-attenuated vaccines throughout the study, including 60 days after the last dose
             of study drug.

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

          8. History of one or more of the following: cardiac insufficiency (New York Heart
             Association [NYHA] III/IV), uncontrolled cardiac arrhythmias, unstable ischemic heart
             disease, or uncontrolled hypertension (systolic blood pressure > 170 mmHg or diastolic
             blood pressure > 110 mmHg).

          9. History of myocardial infarction, or cerebrovascular accident.

         10. Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.

         11. Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or
             significant systemic involvement secondary to rheumatoid arthritis.

         12. Evidence of active malignant disease, malignancies diagnosed within the previous 5
             years, or breast cancer diagnosed within the previous 5 years (except skin cancers
             other than melanoma).

         13. History of human immunodeficiency virus infection or other immunodeficiency illness.

         14. Unstable psychiatric illness defined as psychosis or untreated major depression within
             90 days.

         15. History of drug abuse (not including marijuana use) or alcoholism within the past 12
             months.

         16. Significant neuromuscular disease other than ALS.

         17. Other ongoing disease that may cause neuropathy, such as toxin exposure, dietary
             deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus
             erythematosus or other connective diseases, infection with HIV, hepatitis B virus
             (HBV), or hepatitis C (HCV), Lyme disease, multiple myeloma, Waldenström's
             macroglobulinemia, amyloid, and hereditary neuropathy.

         18. Pregnancy or breastfeeding.

         19. Deprivation of freedom by administrative or court order.

         20. Any contraindication to undergo magnetic resonance imaging (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; or severe claustrophobia.

         21. Unwilling or unable to discontinue benzodiazepine usage [other than lorazepam
             (Ativan®), clonazepam (Klonopin®), or zolpidem (Ambien®)] for one day prior to and
             during scanning.

         22. Research imaging-related radiation exposure exceeds current institutional Radiology
             Department guidelines
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? 0