Evaluating DF-003 for patients with ROSAH syndrome

A Phase Ib, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 in ROSAH Syndrome Patients

This study is testing a new medication called DF-003 to see if it's safe and well-tolerated for people with ROSAH syndrome.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm) (Industry-sponsored)
• Drugs / interventions: imatinib, ceritinib
• Locations: 4 sites (Bethesda, Maryland and 3 other locations)
• Trial ID: NCT06395285 on ClinicalTrials.gov

What this trial studies

This Phase Ib open-label, single-arm study aims to assess the safety and tolerability of DF-003 in patients diagnosed with ROSAH syndrome. A total of up to 12 participants will receive a single daily oral dose of DF-003 for 28 days, with follow-up for 8 weeks post-treatment. The study will monitor pharmacokinetics and pharmacodynamics, ensuring a thorough evaluation of the drug's effects and safety profile. The cohort will consist of a minimum of 6 patients, with the possibility of enrolling additional patients based on safety data reviews.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a confirmed diagnosis of ROSAH syndrome and specific genetic mutations associated with the condition.

Not a fit: Patients who are pregnant, breastfeeding, or planning to conceive may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients suffering from ROSAH syndrome.

How similar studies have performed: While this approach is novel for ROSAH syndrome, similar studies in related conditions have shown promising results.

Eligibility criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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%.
6. Moderate or severe hepatic impairment (categorized as Child-Pugh class B and C, respectively, on the Child-Pugh Score for Cirrhosis Mortality)

Where this trial is running

Bethesda, Maryland and 3 other locations

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Withdrawn)
• Duke Eye Center - Duke University Hospital — Durham, North Carolina, United States (Recruiting)
• John A. Moran Eye Center - University of Utah Health — Salt Lake City, Utah, United States (Recruiting)
• Save Sight Institute - University of Sydney Eye Hospital — Sydney, New South Wales, Australia (Recruiting)

Study contacts

• Study coordinator: Neil Solomons, MD

Conditions ROSAH; ROSAH syndrome; alpha-protein kinase 1; cone-rod dystrophy; macular edema; papillary edema; retinal dystrophy; uveitis