一项评估VT-1953局部凝胶治疗恶臭恶性蕈样伤口患者安全性和疗效的2期试验最终结果

Background: Malignant fungating wound (MFW) is a chronic inflammatory condition that afflicts 5-14% of patients with advanced cancers. MFWs are extremely distressing to patients (pts) given their high burden of symptoms, including extreme malodor and pain. The malodor associated with MFWs has a significant negative effect on quality of life (QOL). Currently, there are no approved treatments for the symptoms of malodorous MFW. There is a need for an effective treatment of symptoms of MFW. Methods: VT-1953 is a dual DNA gyrase and MD2-TLR inhibitor. We tested the safety and efficacy of VT-1953 2% topical gel in an open-label, investigator-initiated phase 2 clinical trial (CTRI/2024/05/066875). Male or female pts aged ≥9 years with a diagnosis of malodorous MFW corresponding to 0, 1 or 2 on the 6-point TELER odor scale, ECOG performance status ≤3, and anticipated survival ≥3 months were eligible. VT-1953 (7.5 g) was applied twice daily to wounds for 14 days; a vehicle arm was included for comparison. The primary endpoint was the change in malodor score associated with MFW from baseline (BL) to Day 14, rated by investigators using the TELER scale. Secondary endpoints were the change in investigator-rated malodor (TELER) at Day 7 from BL. Exploratory endpoints included change in pt-rated malodor (10-point VAS) at Days 7 and 14, change in pain associated with MFW (by pts) using a 10-point VAS and the change in QOL (by pts) using a 10-point VAS on Days 7 and 14 compared to BL. Results: At the time of the final analysis, 15 pts were eligible and included; 10 pts were in the VT-1953 arm and 5 in the vehicle arm. The results are summarized in the Table. There were no treatment-emergent side effects and no severe local skin reactions. Conclusions: Our data indicate that VT-1953 has a favorable safety profile, significantly decreased malodor and pain, and improved the QOL of pts with MFW. These results support VT-1953 as a promising option for the symptomatic management of MFW. Table: Endpoint Arm Baseline median (Q1-Q3 or range) Day 14 median (Q1-Q3 or range) p vs baseline (within arm) p vs vehicle at Day 14 Investigator-rated malodor (TELER 0-High- 5- Low) VT-1953 (Active) 0.5 (0-2.0) 4.0 (3.0-4.0) p = 0.0020 p = 0.0015 Vehicle 1.0 (1.0-2.0) 1.0 (1.0-1.0) not significant (NS) - Patient-rated Malodor (VAS 0-Low - 10-High) VT-1953 (Active) 7.5 (Q1 7.0, Q3 9.0) 2.5 (Q1 2.0, Q3 3.0) p = 0.0020 p = 0.0023 Vehicle 6.0 (Q1 5.0, Q3 6.0) 7.0 (Q1 6.0, Q3 7.0) NS - Patient-rated Pain (VAS 0-Low - 10-High) VT-1953 (Active) 6.0 (Q1 5.0, Q3 7.0) 4.0 (Q1 3.0, Q3 4.0) p = 0.0020 p = 0.0026 Vehicle 6.0 (Q1 6.0, Q3 6.0) 6.0 (Q1 6.0, Q3 6.0) NS - Patient-rated Quality of life (VAS 0-High- 10- Low) VT-1953 (Active) 5.5 (Q1 4.5, Q3 6.0) 3.0 (Q1 2.8, Q3 3.3) p = 0.0020 p = 0.0032 Vehicle 4.8 (Q1 4.3, Q3 4.8) 5.0 (Q1 4.5, Q3 5.0) NS - Values are medians (Q1-Q3 or range). Within-arm p values test change from baseline using Wilcoxon signed-rank tests. Between-arm p values (VT-1953 vs vehicle) compare Day 14 scores using Wilcoxon rank-sum tests.