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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
WITHDRAWNDuke Eye Center - Duke University Hospital
Durham, North Carolina, United States
RECRUITINGJohn A. Moran Eye Center - University of Utah Health
Salt Lake City, Utah, United States
Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Time frame: Baseline to Day 78 (±2)
Frequency and Severity of Serious Adverse Events (SAEs) (Local and Systemic) as Assessed by CTCAE v5.0
Time frame: Baseline to Day 78 (±2)
Eye Uveitis as Measured by Changes in Macular Edema
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Chemokine (C-C motif) ligand CCL2, CCL4, C-X-C motif chemokine ligand (CXCL)-1, CXCL9, CXCL10
Time frame: 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
Time frame: 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)
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Save Sight Institute - University of Sydney Eye Hospital
Sydney, New South Wales, Australia
RECRUITINGChanges 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
Time frame: 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 High-Sensitivity C-reactive Protein (hs-CRP) Levels
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)