A randomised, placebo-controlled, multicentre, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia

Abstract

Objectives: To evaluate the efficacy and safety of three dosing schemes of GV1001 in patients with benign prostatic hyperplasia (BPH).

Patients and methods: Eligible patients were men aged ≥50 years, with an International Prostate Symptom Score (IPSS) of ≥13, maximum urinary flow rate (Q_max ) of 5-15 mL/s, post-void residual urine volume (PVR) of ≤200 mL, and prostate volume of ≥30 mL. After a 4 week run-in period, patients were randomly assigned to one of three treatment schedules: Group 1, GV1001 0.4 mg, 2-week interval; Group 2, GV1001 0.56 mg, 2-week interval; Group 3, GV1001 0.56 mg, 4-week interval) or placebo (Group 4). The eligible patients were administered GV1001 or placebo, for a total of seven intradermal injections that were administered at 2-week intervals at weeks 0, 2, 4, 6, 8, 10, and 12. Treatment continued for 12 weeks, and efficacy was evaluated at weeks 4, 8, 12, 13, and 16. Safety was evaluated throughout the 16-week period. The primary efficacy variable was change from baseline (CFB) in total IPSS. Secondary endpoints were CFB in Q_max , PVR, prostate volume, International Index of Erectile Function score, plasma testosterone level, dihydrotestosterone level, and prostate-specific antigen level.

Results: A total of 161 patients were included (Group 1, n = 41; Groups 2-4, n = 40). Most patients (88.8%) received all planned doses of the study treatment. At week 13, a statistically significant difference in the mean CFB in IPSS was seen in GV1001 treatment Groups 1 and 2 vs the control group for the full analysis population (-3.5 [control] vs -7.2 and -6.8 in Groups 1 and 2, respectively; both P < 0.05). There were also statistically significant differences in CFB at weeks 8, 12, 13, and 16 in treatment Groups 1 and 2 vs control in the per-protocol population. There was a statistically significant reduction in prostate gland volume at week 16 vs control in all treatment groups (0.8 [control] vs -4.6, -2.5, and -4.2 mL in Groups 1-3, respectively; all P < 0.05). There were no statistically significant differences found in other secondary outcome measures. Adverse event (AE) reporting was similar across all four groups. No treatment-emergent AEs were considered to be related to the study drug.

Conclusions: The results indicate that GV1001 was effective and well tolerated, and may provide potential beneficial effects in patients with BPH. Compared with medical therapies that require daily dosing, the convenient dosing regimen of GV1001 may provide greater patient adherence. Further investigation of these observations will require large-scale clinical evaluation.

Keywords: #UroBPH; GV1001; benign prostatic hyperplasia; intradermal injection therapy; lower urinary tract symptoms.