O-027 Efficacy results from the phase II randomized clinical trial: OXO-001 in infertile women undergoing egg donation IVF/ICSI

Abstract Study question Does OXO-001 increase implantation and pregnancy rates in women undergoing egg donation IVF/ICSI and embryo transfer (ET) compared to placebo? Summary answer This proof-of-concept (PoC) prospective randomized and controlled study shows that OXO-001 treatment increases implantation and pregnancy rates in infertile women undergoing IVF/ICSI with studied doses. What is known already OXO-001 is a drug being developed as an innovative treatment to enhance embryo implantation through a direct effect on the endometrium. Preclinical results show an increase in embryo implantation and viability. Moreover, they show that OXO-001 is safe for the mother, the fetuses, and the newborns without any deleterious effect on the development, viability, and implantation potential of OXO-001-exposed embryos. Neither conceptus development nor morphological disturbances have been observed in the deciduas of treated-pregnant mice. Furthermore, clinical trials confirmed that OXO-001 has the necessary wide safety margin and non-complex kinetics, allowing further research on its therapeutic potential in infertility. Study design, size, duration It was a randomized, double-blind, placebo-controlled, and multicenter phase II clinical trial with three parallel arms conducted at 28 European centers (September/2021-January/2023. EudraCT Num:2021-000001-25). A subset of women ≤40 years were analyzed. A total of 173 were randomized in the three study arms (Placebo, 200 and 300mg/day OXO-001). Treatment started one menstrual cycle before the ET cycle and continued until 5 weeks after ET. The results of this communication are focused on the 300mg/day dose. Participants/materials, setting, methods Patients were infertile women (18-40 years; BMI 18-30 kg/m2) eligible for a fresh-single blastocyst (day 5 and ≥3BB) ET resulting from a donor egg. Exclusion criteria include gynecological abnormalities and history of ≥ 2 failed ET, among others. The primary endpoint was ongoing pregnancy rate (OPR). Secondary included biochemical and clinical pregnancy (BPR and CPR), live birth rate (LBR), and safety and tolerability of OXO-001. Main results and the role of chance 111 women were randomized, and 96 performed a single ET (42 Placebo, 54 OXO-001 300mg/day). Higher BPR, CPR, OPR, and LBR per delivery after were observed in the OXO-001 group versus placebo (75.9% vs. 52.4%*, 50.0% vs. 37.5%, 46.3% vs. 35.7%, 42.6% vs. 35.7%, respectively. *p<0.05). The logistic regression analysis showed a statistically significant difference in the BPR for OXO-001 versus placebo (OR 3.03, 95% CI 1.17-7.85; p = 0.022), and a clinically meaningful difference for CPR, OPR, and LBR after a single ET. In safety evaluation, the frequency of treatment-emergent adverse events (TEAEs) assessed as at least possibly related to the study medication were similar between groups (14 for OXO-001 and 10 for placebo). Most TEAEs were mild or moderate in severity. The most common TEAES were headache, nausea and vomiting, gastrointestinal and dizziness. The assigned study medication was well tolerated, and relevant changes in laboratory analyses (hematology and biochemical profile) were not observed. Limitations, reasons for caution This PoC study was designed to define clinically meaningful differences in fertility outcomes and find patient profiles. It was not empowered to find statistical differences in the OPR. An empowered phase III study is needed to confirm the positive results from phase II. Wider implications of the findings his phase II PoC has achieved its objectives showing that OXO-001 increases more than 10% pregnancy rates in infertile women undergoing IVF/ICSI, with a safe and well-tolerated profile. This is a step forward toward the first therapeutic tool to increase embryo implantation and ET success. Trial registration number EudraCT Number: 2021-000001-25