Evaluating the Safety and Tolerability of Orally Administered DF-003 in ROSAH Syndrome Patients

Prior treatment

• Males who plan to father a child or donate sperm while enrolled in this study or within 90 days after the last dose of study drug.
• Females who are pregnant, breastfeeding, planning to become pregnant, or planning to donate eggs while on study medication or within 90 days after the last dose of study drug.
• Use of any of the following prohibited medications:
  • Agents that are known to have systemic anti-inflammatory responses or high risk for nephrotoxicity or hepatotoxicity
  • Moderate CYP3A4 inhibitors: e.g., amiodarone, amprenavir, conivaptan, delavirdine, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, miconazole, verapamil, grapefruit juice, cat's claw (Dolichandra unguis-cati), Echinacea augustifolia, wild cherry, chamomile, licorice
  • Strong CYP3A4 inhibitors: e.g., ceritinib, clarithromycin, cobicistat, elvitegravir/ritonavir, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir, ombitasvir/paritaprevir/ritonavir (and/or dasabuvir), posaconazole, ritonavir, saquinavir/ritonavir, telithromycin, tipranavir/ritonavir, voriconazole.
  • Strong CYP3A4 inducers: apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor/ivacaftor, mitotane, phenytoin, rifampin, St. John's wort.
  • Digoxin
  • Agents known to cause Torsade de Pointes: Disopyramide, procainamide, quinidine, sotalol, azithromycin, clarithromycin, erythromycin, ciprofloxacin, levofloxacin, moxifloxacin, fluconazole, ketoconazole, pentamidine, voriconazole, haloperidol, thioridazine, ziprasidone, citalopram, escitalopram, dolasetron, droperidol, granisetron, and ondansetron
  • Investigational agents (small molecules and oligonucleotides), vaccines, or invasive medical devices within 28 days (4 weeks, or 5 half-lives, whichever is longer) prior to enrollment or having received a biological product within 6 months prior to enrollment.

Other illness

• History of significant hypersensitivity to products related to DF-003 (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Moderate or severe hepatic impairment (categorized as Child-Pugh class B and C, respectively, on the Child-Pugh Score for Cirrhosis Mortality)

Lab values

• Recent (within 3 months prior to screening) or acute changes in the following laboratory values:
  • Platelet count ≤ 120,000/mm3, or
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> ULN
  • Bilirubin (total, direct) \> ULN or
  • International Normalization Ratio (INR) \> ULN, or
  • Serum albumin less than the lower limit of normal, or
  • Estimated creatinine clearance \< 70 mL/min/1.73 m2 at Screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, or
  • Hemoglobin A1c (HbA1c) \> 8%.

• Sufficient understanding of the purpose and procedures required for the study.
• Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
• Genetic testing for ALPK1 mutations that has been shown to be associated with ROSAH syndrome (e.g. T237M or Y254C, or T237A mutations).
• Signs of uveitis (anterior and/or posterior) in the eye (e.g. macula edema, optic nerve edema, retinal vasculitis, or retinal vascular leakage).
• Patients must be deemed healthy except for diagnosis of ROSAH syndrome and its clinical manifestation.
• Patients must be at least 18 years of age but no older than 65 years of age at the time of Screening.