| Eligibility |
Inclusion Criteria:
1. Diagnosis of C9ORF72-associated FTD with documentation of a clinical genetic test
demonstrating the presence of a pathogenic repeat expansion in C9ORF72
2. Age 18 or older
3. Capable of providing informed consent at the Screening Visit and complying with study
procedures throughout the study, in the Principal Investigator's opinion.
4. In the case that the subject lacks the ability to provide informed consent. Informed
consent will be sought from the subject's surrogate representative.
5. Able to safely swallow study drug capsule at screening and throughout study. May use
thickened substances to assist in swallowing drug.
Exclusion Criteria:
1. Clinically significant unstable medical condition (other than FTD) that would pose a
risk to the subject, according to the Principal Investigator's judgment (e.g.,
cardiovascular instability, systemic infection, or clinically significant laboratory
abnormality or ECG changes).
1. Gastrointestinal disease (e.g., gastric or intestinal bypass surgery, jejunostomy
tube, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic
inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that
might interfere with drug absorption or with interpretation of gastrointestinal
AEs.
Gastrostomy tube placement is allowed prophylactically or to supplement
nutrition/hydration but may not be used for study drug administration.
2. Hepatic profile showing any of the following:
i. Serum alanine aminotransferase (ALT) >5 × upper limit of normal (ULN). ii. Serum
aspartate aminotransferase (AST) >5 × ULN. iii. Serum bilirubin >1.5 × ULN. c. Renal
profile showing an estimated creatinine clearance (eClCR) <30 mL/minute (with eClCR to
be calculated by the method at the laboratory performing the serum creatinine test).
2. Presence of a neurodegenerative cognitive or motor syndrome (e.g., Alzheimer's
disease, Parkinson's disease) not related to the C9ORF72 repeat expansion.
3. Presence of unstable psychiatric disease or substance abuse that would impair ability
of the participant to provide informed consent, in the Principal Investigator's
opinion.
4. 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. Active cancer includes cancers
with current disease manifestations or therapy that could adversely affect subject
safety and longevity, create the potential for drug-drug interactions, or compromise
the interpretation of study results.
5. Prior solid organ transplantation.
6. Ongoing immunosuppressive therapy including systemic or enteric corticosteroids at
screening or for the duration of the trial, at the discretion of the site investigator
and medical monitor.
7. Use within 14 days prior to randomization or for the duration of the trial of a strong
inhibitor or inducer of cytochrome P450 (CYP) 3A4 or expected requirement for chronic
use of a strong inhibitor or inducer of CYP3A4 during study therapy (see Table 2 for a
l list of drugs known to be strong inhibitors or inducers of CYP3A4), at the
discretion of the Principal Investigator or Sponsor.
8. Use within 14 days prior to randomization or for the duration of the trial of drug
that is a moderate-to-strong substrate of CYP2C9 (including warfarin, tolbutamide,
phenytoin, glimepiride) or expected requirement for chronic use of such drugs during
study therapy, at the discretion of the Principal Investigator or Sponsor.
9. Use of investigational treatments for FTD (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 Screening Visit.
10. Exposure at any time to any gene therapies under investigation for the treatment of
FTD (off-label use or investigational).
11. 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 =30 days after discontinuing treatment.
12. Anything that would place the subject at increased risk or preclude the subject's full
compliance with or completion of the study, in the Principal Investigator's opinion.
13. If the subject is being re-screened, the disqualifying condition has not been
resolved, or the mandatory wash-out duration has not occurred.
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