Clinical trial: HEALEY ALS Platform Trial - Master Protocol (NCT04297683)

Eligibility criteria:
Inclusion Criteria:

          1. Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported
             probable, or definite ALS defined by revised El Escorial criteria.

          2. Age 18 years or older.

          3. Capable of providing informed consent and complying with study procedures, in the SI's
             opinion.

          4. Time since onset of weakness due to ALS ≤ 36 months at the time of the Master Protocol
             Screening Visit.

          5. Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time of the
             Master Protocol Screening Visit measured by Slow Vital Capacity (SVC), or, if required
             due to pandemic-related restrictions, Forced Vital Capacity (FVC).

          6. Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30
             days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are
             permitted in the study.

          7. Participants must either not take edaravone or have completed at least one cycle of
             edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants
             are permitted in the study.

          8. Participants must have the ability to swallow pills and liquids at the time of the
             Master Protocol Screening Visit and, in the SI's opinion, have the ability to swallow
             for the duration of the study.

          9. Geographically accessible to the site.

        Exclusion Criteria:

          1. Clinically significant unstable medical condition (other than ALS) that would pose a
             risk to the participant, according to SI's judgment (e.g., cardiovascular instability,
             systemic infection, untreated thyroid dysfunction, or clinically significant
             laboratory abnormality or EKG changes).

             Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood
             Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute
             eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x
             109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
             greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2,
             thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.

          2. Presence of unstable psychiatric disease, cognitive impairment, dementia or substance
             abuse that would impair ability of the participant to provide informed consent, in the
             SI's opinion.

          3. Active cancer or history of cancer, except for the following: basal cell carcinoma or
             successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ,
             prostatic carcinoma in situ, or other malignancies curatively treated and with no
             evidence of disease recurrence for at least 3 years.

          4. Use of investigational treatments for ALS (off-label use or active participation in a
             clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior
             to the Master Protocol Screening Visit.

          5. Exposure at any time to any gene therapies under investigation for the treatment of
             ALS (off-label use or investigational).

          6. If female, breastfeeding, known to be pregnant, planning to become pregnant during the
             study, or of child-bearing potential and unwilling to use effective contraception for
             the duration of the trial and for 3 months, or longer as specified in each RSA, after
             discontinuing study treatment.

          7. If male of reproductive capacity, unwilling to use effective contraception for the
             duration of the trial and for 3 months, or longer as specified in each RSA, after
             discontinuing study treatment.

          8. Anything that would place the participant at increased risk or preclude the
             participant's full compliance with or completion of the study, in the SI's opinion.

          9. If a participant is being re-screened, the disqualifying condition has not been
             resolved, or the mandatory wash-out duration has not occurred.

         10. For those participating in the optional CSF collection, contraindication to undergoing
             a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be
             currently taking anticoagulation medications such as warfarin that would be a
             contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed.
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.


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? Entailment