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

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

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.

Study Overview

• Status: Recruiting
• Conditions: ROSAH
• Intervention / Treatment: Drug: DF-003

Detailed Description

This is a Phase Ib open-label, single-arm, single-dose study that will be conducted in up to 12 ROSAH syndrome patients. The study will investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DF-003 (study drug). DF-003 will be administered orally (PO), once daily (QD) for 28 days (4 weeks). Patients will be followed up for 8 weeks after administration of the last dose of study drug.

A total of 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 after a review of safety data by the Study Safety Committee. Patients will receive loading doses of 140 mg DF-003 on Days 1, 2, and 3, followed by a maintenance dose of 45 mg DF-003 starting on Day 4 through Day 28. Individual dose modification is not allowed in this study.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kenneth Truitt, MD; Phone Number: 732-221-7104; Email: kenneth.truitt@drug-farm.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Recruiting
      • Save Sight Institute - University of Sydney Eye Hospital
      • Contact: Sarah Hussain; Phone Number: +61 2 9382 7300; Email: Sarah.hussain@sydney.edu.au
      • Principal Investigator: John Grigg, MBBS, MD, FRANZCO FRACS
• China
  • Beijing, China, 100730
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Prof. Sui Ruifang; Email: hrfsui@163.com
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Withdrawn
      • National Institutes of Health Clinical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Eye Center - Duke University Hospital
      • Contact: Ethel Cuenca; Phone Number: 919 660 3522; Email: ethel.garcia@duke.edu
      • Principal Investigator: Oleg Alekseev, MD, PhD
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • John A. Moran Eye Center - University of Utah Health
      • Contact: Lucia Lucci; Phone Number: 801-585-6647; Email: lucia.lucci@hsc.utah.edu
      • Principal Investigator: Kathleen Digre, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DF-003; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 High-Sensitivity C-reactive Protein (hs-CRP) 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)
Maximum Plasma Concentration (Cmax) of DF-003		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Time to Reach Maximum Plasma Concentration (Tmax) of DF-003		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to time t (AUC0-t)		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to the time of the last quantifiable concentration (AUC0-last)		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Area Under the Concentration-Time Curve (AUC) of DF-003 from time zero to infinity (AUC0-inf, first dose only)		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Terminal Phase Half-Life (t1/2)		Day 1 (-1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 2 (24 hours post-dose), 8(±2), 15(±2), 22(±2), 28(±2; -1, 0.5, 1, 2, 4, 6, 8, and 12 hours relative to dosing), 29(±2; 24 hours post-dose), 36(±2), 50(±2), 64(±2), 78(±2)
Changes in Serum Chemokine Levels	Chemokine (C-C motif) ligand CCL2, CCL4, C-X-C motif chemokine ligand (CXCL)-1, CXCL9, CXCL10	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 Serum Cytokine Levels	Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-2RA soluble, IL-18, Tumor Necrosis Factor (TNF)-Alpha	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 Serum Serum Amyloid A (SAA) Levels	Serum Amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Headache Impact Test-6 (HIT-6) Scores	To evaluate the effects of DF-003 on headache in ROSAH syndrome patients. Test scores range from 36 to 78, with larger scores reflecting greater impact. Little or no impact = HIT-6 score of 49 or less; some impact = HIT-6 score of 50-55; substantial impact = HIT-6 score of 56-59; severe impact = HIT-6 score > 60.	Baseline to Day 28 (±2)
Change in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Scores	To evaluate the effects of DF-003 on health-related quality of life in ROSAH syndrome patients. This test assesses frequency of symptoms on a 7-point scale (0=no impairment, 6=maximum impairment).	Baseline to Day 28 (±2)
Changes in Eye Anterior Chamber Aqueous Fluid Chemokine Levels	Eye anterior chamber fluid collection is optional and will be collected for assessment of chemokine (C-C motif) ligand CCL2, CCL3, CCL4, CCL5, C-X-C motif chemokine ligand (CXCL)-1, CXCL9, CXCL10	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	Eye anterior chamber fluid collection is optional and will be collected for assessment of Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-2RA soluble, IL-18, Tumor Necrosis Factor (TNF)-Alpha, Serum Amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) 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	Eye anterior chamber fluid collection is optional and will be collected for assessment of Serum Amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) 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 High-Sensitivity C-reactive protein (hs-CRP) levels	Eye anterior chamber fluid collection is optional and will be collected for assessment of high-sensitivity C-reactive protein (hs-CRP) 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)

Collaborators and Investigators

• Sponsor: Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)
• Investigators: Principal Investigator: Kathleen Digre, University of Utah (Moran Eye Center); Principal Investigator: Oleg Alekseev, Duke University (Duke Eye Center); Principal Investigator: John Grigg, University of Sydney (Save Sight Institute); Principal Investigator: Simon Chatfield, Melbourne Health

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: macular edema; uveitis; cone-rod dystrophy; papillary edema; retinal dystrophy; ROSAH syndrome; alpha-protein kinase 1; T237M
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Uveal Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cone-Rod Dystrophies; Uveitis; Macular Edema; Retinal Dystrophies
• Other Study ID Numbers: DF-003-1002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No