NCT06395285招募中1 期
A Phase Ib, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 in ROSAH Syndrome Patients
Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)9 个研究点 分布在 3 个国家目标入组 12 人开始时间: 2025年5月27日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
As this is an open label study, there are no blinding requirements for safety data.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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
- •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%.
- •Moderate or severe hepatic impairment (categorized as Child-Pugh class B and C, respectively, on the Child-Pugh Score for Cirrhosis Mortality)
研究组 & 干预措施
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.
干预措施: DF-003 (Drug)
结局指标
主要结局
Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
时间窗: Baseline to Day 78 (±2)
Frequency and Severity of Serious Adverse Events (SAEs) (Local and Systemic) as Assessed by CTCAE v5.0
时间窗: Baseline to Day 78 (±2)
次要结局
- 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))
- Changes in Serum 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 Serum 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))
- 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))
研究者
研究点 (9)
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相关资讯
Drug Farm Secures $55 Million Series D to Advance AI-Discovered First-in-Class Candidates DF-003 and DF-006- Drug Farm completed the first closing of a $55 million Series D financing co-led by Shanghai Pudong Leading Area Investment Center and Shanghai Puxing Collaborative Private Equity Fund Partnership Enterprise.
- Proceeds will support pivotal development of DF-003, an ALPK1 inhibitor for ROSAH syndrome entering Phase 3, and clinical proof-of-concept in atherosclerotic cardiovascular disease.
- DF-003 is among the first AI-discovered drugs to advance toward late-stage clinical development and holds FDA Fast Track, Orphan Drug, and Rare Pediatric Disease designations.
- Additional funding will continue clinical development of DF-006, an oral ALPK1 agonist immunomodulator, for chronic hepatitis B.2 months agoDrug Farm's DF-003 Receives FDA Fast Track Designation for ROSAH Syndrome Treatment- Drug Farm announced that the FDA has granted Fast Track designation to DF-003, a first-in-class ALPK1 inhibitor for treating ROSAH syndrome, a rare autoinflammatory disease with no approved therapies.
- DF-003 is a structurally novel, orally administered small-molecule inhibitor that crosses blood-retina and blood-brain barriers and significantly suppresses inflammatory cytokines in preclinical models.
- The drug has completed Phase 1 trials in healthy volunteers and is currently enrolling patients in a Phase 1b clinical trial, with results expected to be reported in 2026.
- ROSAH syndrome is a rare genetic disease characterized by progressive visual loss, optic nerve pathology, and systemic inflammation, typically beginning in childhood or early adulthood.7 months agoDrug Farm's DF-003 Shows Promising Safety Profile in Phase 1 Trial for Rare ROSAH Syndrome- Drug Farm reported positive Phase 1 results for DF-003, a first-in-class ALPK1 inhibitor targeting ROSAH syndrome, showing excellent safety with no serious adverse events across all tested doses.
- The randomized, placebo-controlled study in 48 healthy volunteers demonstrated dose-proportional pharmacokinetics supporting once-daily oral administration for future trials.
- DF-003 achieved blood concentrations consistent with efficacy in preclinical models, positioning the company to advance into proof-of-concept trials for ROSAH syndrome and cardio-renal disease.
- The drug represents a potential breakthrough for ROSAH syndrome, a rare genetic disease with no approved treatments that causes progressive vision loss and inflammatory symptoms.last year