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

NCT06395285 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DF-003-1002
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of DF-003 in retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome patients.

Conditions

ROSAH

Keywords

ROSAH syndrome; alpha-protein kinase 1; cone-rod dystrophy; macular edema; papillary edema; retinal dystrophy; uveitis; T237M

Outcome Measures

Primary Outcomes (2)

• Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

  Baseline to Day 78 (±2)

• Frequency and Severity of Serious Adverse Events (SAEs) (Local and Systemic) as Assessed by CTCAE v5.0

  Baseline to Day 78 (±2)

Secondary Outcomes (14)

• Eye Uveitis as Measured by Changes in Macular Edema

  Baseline, Day 1, Day 2, Day 8 (±2), Day 15 (±2), Day 22 (±2), Day 28 (±2), Day 50 (±2), Day 78 (±2)

• Eye Uveitis as Measured by Changes in Optic Nerve Edema

  Baseline, Day 1, Day 2, Day 8 (±2), Day 15 (±2), Day 22 (±2), Day 28 (±2), Day 50 (±2), Day 78 (±2)

• Eye Uveitis as Measured by Changes in Retinal Vasculitis

  Baseline, Day 1, Day 2, Day 8 (±2), Day 15 (±2), Day 22 (±2), Day 28 (±2), Day 50 (±2), Day 78 (±2)

• Eye Uveitis as Measured by Changes in Retinal Vascular Leakage

  Baseline, Day 1, Day 2, Day 8 (±2), Day 15 (±2), Day 22 (±2), Day 28 (±2), Day 50 (±2), Day 78 (±2)

• Changes in Serum Chemokine Levels

  Day 1 (±30 minutes prior to dosing), Day 29 (24 hours relative to dosing on Day 28), and Day 78 (approximately same time as Day 29 collection)

Other Outcomes (6)

• Changes in Eye Anterior Chamber Aqueous Fluid Chemokine Levels

  Day 1 (±30 minutes prior to dosing), Day 29 (24 hours relative to dosing on Day 28), and Day 78 (approximately same time as Day 29 collection)

• Changes in Eye Anterior Chamber Aqueous Fluid Cytokine Levels

  Day 1 (±30 minutes prior to dosing), Day 29 (24 hours relative to dosing on Day 28), and Day 78 (approximately same time as Day 29 collection)

• Changes in Eye Anterior Chamber Aqueous Fluid Serum Amyloid A (SAA) Levels

  Day 1 (±30 minutes prior to dosing), Day 29 (24 hours relative to dosing on Day 28), and Day 78 (approximately same time as Day 29 collection)

Study Arms (1)

DF-003

EXPERIMENTAL

Oral (PO) doses of 140 mg DF-003 on Days 1, 2, and 3 followed by a maintenance dose of 45 mg DF-003 once daily (QD) starting on Day 4 through Day 28. DF-003 will be administered PO with approximately 240 mL of water in the morning once daily for 28 consecutive days.

Drug: DF-003

Interventions

DF-003 DRUG

140 mg on Days 1, 2, and 3 followed by a maintenance dose of 45 mg QD starting on Day 4 through Day 28. DF-003 will be administered PO with approximately 240 mL of water in the morning once daily for 28 consecutive days.

DF-003

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm): lead

Study Sites (4)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

WITHDRAWN

Duke Eye Center - Duke University Hospital

Durham, North Carolina, 27705, United States

RECRUITING

John A. Moran Eye Center - University of Utah Health

Salt Lake City, Utah, 84132, United States

RECRUITING

Save Sight Institute - University of Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

RECRUITING

MeSH Terms

Conditions

Cone-Rod Dystrophies; Macular Edema; Retinal Dystrophies; Uveitis

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Macular Degeneration; Uveal Diseases

Central Study Contacts

Neil Solomons, MD

CONTACT

+12502173267; neil.solomons@drug-farm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: As this is an open label study, there are no blinding requirements for safety data.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ROSAH syndrome patients will receive oral (PO) doses of DF-003 once daily (QD) for a duration of 28 days (4 weeks). In this study, 8 patients will be evaluated in one cohort. The cohort will have a minimum of 6 patients. Additional patients (maximum of 12 patients) may be enrolled in the event of insufficient data. Patients will receive loading doses of 140 mg on Days 1, 2, and 3, followed by a maintenance dose of 45 mg QD starting on Day 4 through Day 28. Individual dose modification is not allowed in this study. If the overall cohort dose needs modification, this will be determined based on review of all available safety and pharmacokinetics (PK) data from this study.

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 2, 2024
• Study Start: May 27, 2025
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (1)