Evaluating the Safety and Tolerability of Orally Administered DF-003 in ROSAH Syndrome Patients
- Conditions
- ROSAH
- Registration Number
- NCT06395285
- Lead Sponsor
- Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 12
Inclusion Criteria:<br><br> 1. Sufficient understanding of the purpose and procedures required for the study.<br><br> 2. Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.<br><br> 3. Genetic testing for ALPK1 mutations that has been shown to be associated with ROSAH<br> syndrome (e.g. T237M or Y254C, or T237A mutations).<br><br> 4. Signs of uveitis (anterior and/or posterior) in the eye (e.g. macula edema, optic<br> nerve edema, retinal vasculitis, or retinal vascular leakage).<br><br> 5. Patients must be deemed healthy except for diagnosis of ROSAH syndrome and its<br> clinical manifestation.<br><br> 6. Patients must be at least 18 years of age but no older than 65 years of age at the<br> time of Screening.<br><br>Exclusion Criteria:<br><br> 1. Males who plan to father a child or donate sperm while enrolled in this study or<br> within 90 days after the last dose of study drug.<br><br> 2. Females who are pregnant, breastfeeding, planning to become pregnant, or planning to<br> donate eggs while on study medication or within 90 days after the last dose of study<br> drug.<br><br> 3. Use of any of the following prohibited medications:<br><br> - Agents that are known to have systemic anti-inflammatory responses or high risk<br> for nephrotoxicity or hepatotoxicity<br><br> - Moderate CYP3A4 inhibitors: e.g., amiodarone, amprenavir, conivaptan,<br> delavirdine, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib,<br> miconazole, verapamil, grapefruit juice, cat's claw (Dolichandra unguis-cati),<br> Echinacea augustifolia, wild cherry, chamomile, licorice<br><br> - Strong CYP3A4 inhibitors: e.g., ceritinib, clarithromycin, cobicistat,<br> elvitegravir/ritonavir, idelalisib, indinavir/ritonavir, itraconazole,<br> ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir,<br> paritaprevir/ritonavir, ombitasvir/paritaprevir/ritonavir (and/or dasabuvir),<br> posaconazole, ritonavir, saquinavir/ritonavir, telithromycin,<br> tipranavir/ritonavir, voriconazole.<br><br> - Strong CYP3A4 inducers: apalutamide, carbamazepine, enzalutamide, ivosidenib,<br> lumacaftor/ivacaftor, mitotane, phenytoin, rifampin, St. John's wort.<br><br> - Digoxin<br><br> - Agents known to cause Torsade de Pointes: Disopyramide, procainamide,<br> quinidine, sotalol, azithromycin, clarithromycin, erythromycin, ciprofloxacin,<br> levofloxacin, moxifloxacin, fluconazole, ketoconazole, pentamidine,<br> voriconazole, haloperidol, thioridazine, ziprasidone, citalopram, escitalopram,<br> dolasetron, droperidol, granisetron, and ondansetron<br><br> - Investigational agents (small molecules and oligonucleotides), vaccines, or<br> invasive medical devices within 28 days (4 weeks, or 5 half-lives, whichever is<br> longer) prior to enrollment or having received a biological product within 6<br> months prior to enrollment.<br><br> 4. History of significant hypersensitivity to products related to DF-003 (including<br> excipients of the formulations) as well as severe hypersensitivity reactions (like<br> angioedema) to any drugs.<br><br> 5. Recent (within 3 months prior to screening) or acute changes in the following<br> laboratory values:<br><br> - Platelet count = 120,000/mm3, or<br><br> - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > ULN<br><br> - Bilirubin (total, direct) > ULN or<br><br> - International Normalization Ratio (INR) > ULN, or<br><br> - Serum albumin less than the lower limit of normal, or<br><br> - Estimated creatinine clearance < 70 mL/min/1.73 m2 at Screening, calculated by<br> the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, or<br><br> - Hemoglobin A1c (HbA1c) > 8%.<br><br> 6. Moderate or severe hepatic impairment (categorized as Child-Pugh class B and C,<br> respectively, on the Child-Pugh Score for Cirrhosis Mortality)
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0;Frequency and Severity of Serious Adverse Events (SAEs) (Local and Systemic) as Assessed by CTCAE v5.0
- Secondary Outcome Measures
Name Time Method Eye Uveitis as Measured by Changes in Macular Edema;Eye Uveitis as Measured by Changes in Optic Nerve Edema;Eye Uveitis as Measured by Changes in Retinal Vasculitis;Eye Uveitis as Measured by Changes in Retinal Vascular Leakage;Changes in Serum Chemokine Levels;Changes in Serum Cytokine Levels;Changes in Serum Serum Amyloid A (SAA) Levels;Changes in Serum High-Sensitivity C-reactive Protein (hs-CRP) Levels;Maximum Plasma Concentration (Cmax) of DF-003;Time to Reach Maximum Plasma Concentration (Tmax) of DF-003;Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to time t (AUC0-t);Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to the time of the last quantifiable concentration (AUC0-last);Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to infinity (AUC0-inf, first dose only);Terminal Phase Half-Life (t1/2)