| Eligibility |
Inclusion Criteria:
1. Diagnosis of ALS classified as Clinically Probable ALS or Clinically Definite ALS
according to the El Escorial Revised Criteria4
2. ALS onset = 18 months from Screening
3. Male or female aged 20 to 80 years old (inclusive)
4. ALSFRS-R = 30
5. SVC = 60% of predicted at Screening
6. Willing and able to provide informed consent
7. Concurrent medications riluzole and edaravone are permitted as long as the regimen is
stable for at least 4 weeks prior to randomization and is expected to remain unchanged
during the course of the study
8. Able to swallow tablets
9. Has been stable on medications that affect the CNS, for at least 4 weeks (including
antidepressants, hypnotics and antipsychotics) and dose is not expected to change
during the trial
10. Willing to abstain from benzodiazepine or other CNS depressant treatment for 24 hours
prior to each clinic visit and night-time hypnotics for 8 hours prior to each clinic
visit
11. Negative serum pregnancy test at Screening, for female subjects of childbearing
potential
12. Male subjects:
Male subjects with female partners of childbearing potential are eligible to participate if
they agree to ONE of the following methods of contraception from 21 days before the first
dose of IMP through 4 months after the last dose of the IMP:
- Abstinence from penile-vaginal intercourse as their usual and preferred lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent
- Use of a male condom plus partner use of a contraceptive method with a failure rate of
< 1% per year when having penile-vaginal intercourse with a woman of childbearing
potential who is not currently pregnant.
In addition male subjects must refrain from donating sperm for the duration of the study
and for 4 months after the last dose of the IMP.
Female subjects:
A female subject is eligible to participate if she is not pregnant and/or breastfeeding.
Females of childbearing potential must agree to use a highly effective method of
contraception consistently and correctly during the treatment period and for at least 3
months after the last dose of IMP.
Highly effective methods of contraception include, combined hormonal (estrogen and
progestogen containing) contraception, which may be oral, intravaginal, or transdermal,
progestogen-only hormonal contraception associated with inhibition of ovulation, which may
be oral, injectable, or implantable, placement of an intrauterine device, placement of an
intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner and
true sexual abstinence, if it is the chosen life style of the subject.
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus
interruptus), spermicides only and the lactational amenorrhea method are not acceptable
methods of contraception. Female condom and male condom should not be used together
Exclusion Criteria:
1. Dependence on invasive or non-invasive mechanical ventilation (excluding continuous
positive airway pressure for sleep apnea)
2. Has current serious or unstable illnesses including cardiovascular, hepatic, renal,
gastroenterological, respiratory, endocrinologic, neurologic (other than ALS),
psychiatric, infectious, immunologic or hematologic disease and other conditions that,
in the investigator's opinion, could interfere with the analyses of safety and
pharmacologic effect in this study
3. Has a life expectancy of <1 years
4. Has had a history within the last 5 years of a serious infectious disease affecting
the brain or head trauma resulting in protracted loss of consciousness
5. Has a history within the last 5 years of a primary or recurrent malignant disease with
the exception of resected cutaneous squamous cell carcinoma in situ, basal cell
carcinoma, cervical carcinoma in situ or in situ prostate cancer with a normal
prostate specific antigen post treatment
6. Has a known history of human immunodeficiency virus, clinically significant multiple
or severe drug allergies or severe post treatment hypersensitivity reactions
7. Has a "yes" answer to Columbia Suicide Severity Rating Scale (C-SSRS) suicidal
ideation item 4 or 5, or any suicidal behavior assessment within 6 months of
Screening, or has been hospitalized or treated for suicidal behavior in the past 5
years before Screening
8. Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
9. Transient ischemic attack or stroke or any unexplained loss of consciousness within 1
year prior to Screening
10. History of bleeding disorder or predisposing conditions, blood clotting or clinically
significant abnormal results on coagulation profile at Screening, as determined by the
investigator
11. History of unstable angina, myocardial infarction, chronic heart failure (New York
Heart Association Class III or IV) or clinically significant conduction abnormalities
(e.g., unstable atrial fibrillation) within 1 year prior to Screening
12. Clinically significant 12 lead electrocardiogram (ECG) abnormalities, as determined by
the investigator
13. Indication of impaired liver function as shown by an abnormal liver function profile
at Screening (e.g., repeated values of aspartate aminotransferase [AST] and alanine
aminotransferase [ALT] = 2 × the upper limit of normal [ULN] and/or indication of
impaired renal function at Screening) (e.g., repeated values of creatinine and blood
urea nitrogen [BUN] = 1.5 × ULN or estimated glomerular filtration rate [GFR] < 45
mL/minute/1.73 m2 and corroborating medical history and physical examination)
14. Any contraindications to lumbar puncture (LP), e.g., increased bleeding risk (platelet
count < 100,000/µL, coagulopathies, anticoagulant drugs, antiplatelet therapy), lumbar
spine deformity that might interfere with the procedure, evidence on magnetic
resonance imaging (MRI) contraindicating LP, risk for cerebral herniation, space
occupying lesion with mass effect, abnormal intracranial pressure due to increased CSF
pressure, Arnold Chiari malformation, local infections at the puncture site and
subject refusal of LP; abnormalities in the Screening CSF profile that are considered
by the investigator to be clinically significant are exclusionary
15. Any major surgery or trauma within 12 weeks of Screening or during the Screening
Period or any surgery planned during the study
16. Has active ocular condition, that in the opinion of the investigator, may alter visual
acuity during the course of the study
17. Use of any drugs that are strong inhibitors of cytochrome (CYP) 450 (2D6 or 2C19)
within 7 days or 5 half-lives of the inhibitor (whichever is longer), prior to
administration of the first dose of IMP and/or plan to use throughout the study
18. Has taken other investigational drugs or participated in any clinical study within 30
days or 5 half-lives (if known) of the investigational drug, whichever is longer,
prior to first dose of IMP in this study or is currently participating in another
clinical study
19. Other unspecified reasons that, in the opinion of the investigator or Samus and/or its
delegated medical monitor, place the subject at risk or make the subject unsuitable
for the study or unable or unwilling to comply with the requirements of the study
20. Female subject of childbearing potential with positive pregnancy test or who is
lactating
21. History or presence of conditions, which in the judgment of the investigator, are
known to interfere with the absorption distribution, metabolism or excretion of drugs,
such as prior surgery or gastrointestinal dysfunction that may affect drug absorption
(e.g., gastric bypass surgery, gastrectomy)
22. History of serious head injuries, unexplained syncope, loss of consciousness, CNS
disease or dementia
23. Prior exposure to PU-AD or related compounds
24. Significant blood loss (> 450 mL) or has donated one or more units of blood or plasma
within 6 weeks prior to study participation
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