A Study of Single Ascending Doses of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS)

Lab values

• • Positive test for, or history of, human immunodeficiency virus.
  • Positive test for, or history of, hepatitis C antibody, or hepatitis B (positive for both surface antigen and core antibody).
  • Prior treatment with another investigational drug, biologic or device within 1 month or 5 half-lives, whichever is longer. Prior use of siRNA, stem cell therapy or gene therapy is prohibited.
  • Currently enrolled in another interventional study.
  • Current or anticipated need for a diaphragm pacing system, per Investigator judgment.
  • History of drug or alcohol abuse within 6 months that may interfere with study participation.
  • Presence of a tracheostomy.
  • Known active infection requiring systemic antiviral or antimicrobial therapy during screening.
  • An ongoing medical condition, for example cachexia or severe anemia, that may interfere with study conduct or assessments.
  • Pregnancy or breastfeeding at screening or at admission.
  • Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, for example psychosis, suicidal ideation, suicide attempt, or untreated major depression within 90 days.
  • History of broad anesthetic allergies.
  • Increased or uncontrolled bleeding risk, including anatomical abnormalities near the lumbar puncture site or coagulation disorders.
  • Anticipated need for antiplatelet or anticoagulant therapy within 7 days before or 48 hours after lumbar puncture.
  • Presence of an implanted cerebrospinal fluid shunt or central nervous system catheter.
  • Clinically significant hematology or chemistry abnormalities, per Investigator judgment.
  • Significant ECG abnormalities, including QTcF greater than 450 ms in males or greater than 460 ms in females.
  • Estimated glomerular filtration rate below 60 mL/min/1.73 m2 at screening by the CKD-EPI equation, or known chronic kidney disease stage 3 or above, nephrotic syndrome, or chronic glomerulonephritis.
  • AST or ALT greater than 2 times the upper limit of normal at screening; or total bilirubin greater than 1.5 times the upper limit of normal at screening, except in Gilbert syndrome; or known cirrhosis, chronic active hepatitis or hepatic insufficiency.
  • Known hypersensitivity, allergy or adverse reaction to gold or gold-containing compounds. NI112 contains gold nanoparticles.
  • Currently receiving tofersen, or received tofersen within 6 months before screening.
  • Inability to comply with study requirements.
  • Any other condition or circumstance deemed unsuitable by the Investigator or Sponsor.

• • Able to understand the purpose and risks of the study and to provide signed, dated informed consent and authorization for use of protected health information. A legally authorized representative may consent if the subject is legally unable to do so.
  • Aged ≥ 18 years at the time of informed consent. No upper age limit.
  • Weakness attributable to ALS and a diagnosis of possible, laboratory-supported probable, probable or definite ALS per the revised El Escorial criteria (Airlie House, 1998).
  • Forced vital capacity ≥ 50% of predicted, adjusted for sex, age, height and sitting position. Subjects with a stable forced vital capacity of 45 to 49% with no more than 5% decline over 6 months may be eligible at the Investigator's discretion.
  • If taking riluzole, on a stable dose for more than 30 days before Day 1 and expected to remain on that dose through study completion.
  • Medically able to undergo the study procedures and to adhere to the visit schedule and study restrictions, as determined by the Investigator.
  • Screening platelet count, INR, PT and APTT within normal limits. A single repeat test is allowed if initial values are marginally abnormal, per Investigator judgment.
  • Sexually active females of childbearing potential and non-sterile males must agree to use effective contraception during the study and for 90 days after the final dose. Males, including those who have had a vasectomy, with a pregnant partner must use a condom from the first dose and for 90 days after, and must not donate sperm for 90 days after the final dose.