Clinical Trials

Inclusion Criteria:

• Males or females ≥ 18 years of age at the time of informed consent.
• Have documentation of a clinical genetic test demonstrating the presence of a confirmed repeat expansion in the C9orf72 gene from a CLIA certified laboratory.
• Body weight range of ≥ 41 kg (90 lbs) to ≤ 118 kg (260 lbs).
• Score ≥ 18 on the Mini-Mental State Exam (MMSE) at Screening.
• If female, must be postmenopausal (for at least 2 years), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception from Screening through Week 52.
• If male, with a partner who is not postmenopausal (for at least 2 years) or surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), the patient must agree that he and his partner
• will use highly effective methods of contraception from Screening through Week 52.
• Able to perform all protocol-specified assessments, including neuropsychological tests; and comply with taking study medication and the study visit schedule, as judged by the investigator.
• Have a reliable caregiver to accompany the patient to all study visits. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and informant-based assessments of the patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study.
• Able to understand and provide written informed consent at Screening.
• Agree to allow data sharing across observational longitudinal and interventional studies using an Nencrypted global unique identifier (GUID) so that potential prior or future data on biomarkers and disease progression can be made accessible to the sponsor.
• Stable doses of all concomitant medications for 1 month prior to Screening (e.g., edaravone, riluzole, dextromethorphan/quinidine, psychotropic medications, cognitive enhancers, etc.). 
• For patients with ALS (with or without FTD):
  • Diagnosis of ALS (probable, possible, laboratory-supported probable or definite) according to the World Federation of Neurology revised E1 Escorial criteria.
• Onset of weakness within 3 years prior to Screening.
• Slow vital capacity (SVC) ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position).
• Able to perform reproducible pulmonary function tests.
• ALS Functional Rating Scale-Revised (ALSFRS-R) ≥ 30 at Screening
• For patients with FTD:
  • A gradual, progressive decline in behavior, language, or motor function consistent with C9orf72 hexanucleotide expansion-related syndrome such as behavioral variant FTD, primary progressive aphasia, or amnestic syndrome.
• CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD) global score of 0.5-2.0 at Screening.

Exclusion Criteria:

• Presence of other significant neurological or psychiatric disorders including (but not limited to) biomarker confirmed Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease; multiple sclerosis; a primary or severe psychotic disorder; severe bipolar or unipolar depression; prior history of suicidal thoughts or behavior that are believed to represent a current safety risk; seizure; brain tumor or other space-occupying lesion; history of stroke; or history of severe head injury within the past 20 years.
• History of significant brain abnormality, including, but not limited to, prior hemorrhage or infarct, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma); symptoms or signs of elevated intracranial pressure; e.g., symptoms or history of head injury or abnormal funduscopic exam. If there is history or evidence on neurologic exam suggesting possible subdural hematoma (SDH), patients should be fully evaluated, including magnetic resonance imaging (MRI) if indicated, to exclude significant, new SDH.
• Active alcohol, drug abuse or substance abuse, or any other reason that makes it unlikely that the patient will comply with study procedures in the opinion of the investigator.
• Clinically significant findings on Screening laboratory testing, physical examination or vital signs that are not specific to ALS/FTD that could interfere with the conduct of the study, the interpretation of the data, or increase patient risk.
• Clinically significant intercurrent illness or medical condition (e.g., hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease) that would jeopardize the safety of the patient, limit participation, or compromise the interpretation of the data derived from the patient.
• History of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C, or any active infection.
• History of cancer within 5 years of Screening, with the exception of fully excised non-melanoma skin cancers.
• Receipt of an investigational agent within 30 days or 5 half-lives prior to Screening, whichever is longer.
• Prior treatment with any monoclonal antibody within 6 months of Screening.
• Receipt of systemic corticosteroids within 30 days prior to Screening.
• Any vaccination within 30 days prior to study drug administration.
• Has smoked or used tobacco products within 6 months prior to study drug administration.
• Hypertension, defined as confirmed systolic blood pressure (SBP) > 170 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg at Screening.
• Hypotension, defined as confirmed SBP < 90 mmHg and/or DBP < 60 mmHg at Screening.
• Any major surgery within 4 weeks of Screening.
• Females who are pregnant (positive pregnancy test at Screening or prior to administration of study drug), breastfeeding, or unable or unwilling to use highly effective methods of contraception throughout the study.
• Contraindication to undergoing a lumbar puncture (LP) including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of < 120,000/μL; infection at the desired LP site; taking anti-platelet or anti-coagulant medication within 30 days of Screening.
  • Note: aspirin is permitted); severe degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
• Allergy to any of the components of the study drug.
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Physical and laboratory test findings, including the following:
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory determinations beyond what is consistent with the target population;
  • Clinically significant abnormality on 12-lead ECG prior to study drug administration, confirmed by repeat testing;
  • Total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), confirmed by repeat testing;
  • Serum creatinine > 168μmol/L (1.9mg/dL), confirmed by repeat testing;
  • Hematocrit < 35% for males and < 32% for females, absolute neutrophil cell count of < 1500/μL;
  • Clinically significant abnormal thyroid stimulating hormone (TSH) test;
  • Abnormally increased number of white blood cells (> 7 cells/mm^3) in the CSF obtained at the Screening Visit; if there is evidence that the spinal tap was traumatic, patients with > 7 cells/mm^3 must be discussed with the medical monitor to determine if they may be eligible;
  • Hemoglobin A1C >7%, confirmed by repeat testing;
  • Positive blood screen for HIV, hepatitis C antibody, or hepatitis B surface antigen.

Eligibility last updated 8/30/21. Questions regarding updates should be directed to the study team contact.