O-021 Magnetic Resonance Imaging (MRI) evaluation of Quinagolide Vaginal Ring (QVR) treatment on endometrioma, Deep Infiltrating Endometriosis (DIE), and adenomyosis lesion characteristics: QLARITY trial results
Authors: Pellicer A , Taylor H S , Alberich-Bayaari Á , Liu Y , Gamborg M , Barletta K , Heiser P W , Pinton P , Bagger Y W 
Published: July 2024

Abstract

Study question
Can MRI provide a useful assessment of changes to endometrioma, DIE, and adenomyosis lesion burden resulting from QVR treatment?

Summary answer
MRI successfully measured changes in the number, size, diffusion, and perfusion biomarkers of endometriotic and adenomyotic lesions enabling evaluation of QVR treatment efficacy.

What is known already
Endometriosis and adenomyosis are associated with chronic pelvic pain, painful menses, and infertility. Determining treatment efficacy is reliant on patient reported outcomes (PRO) which are sensitive to response style effects and may lag changes in underlying pathology. Availability of biomarkers measuring lesion burden could accelerate the development of therapies treating disease rather than managing symptoms. MRI is routinely used in oncology to provide non-invasive biomarkers of treatment effect, a paradigm adapted in this trial. Quinagolide is a dopamine D2 receptor agonist formulated in an extended-release vaginal ring in development for treatment of endometriosis based on presumed inhibition of lesion angiogenesis.

Study design, size, duration
QLARITY was a randomized, placebo-controlled phase 2 trial investigating the mechanism of action of QVR (1080 µg) administered for four menstrual cycles. Randomization was 1:1 QVR (n = 35) to placebo vaginal ring (n = 32). Primary endpoint was change in the sum of lesion sizes by type from baseline to end of cycle 4 as measured by MRI. Secondary endpoints included changes in lesion volume, PROs and adverse events. MRI-derived imaging biomarkers were analyzed as exploratory endpoints.

Participants/materials, setting, methods
Women, 18-45 years old with at least one type of lesion (endometrioma, adenomyosis, and/or DIE) visualized by MRI, were enrolled. The analyses were performed by treatment for each of the three lesion types individually and for all types combined. Change in lesion size was analyzed using ANCOVA adjusted for baseline. Number of subjects with lesion regression was analyzed using a Chi-Square test. MRI-derived diffusion and perfusion imaging biomarkers were analyzed as exploratory endpoints.

Main results and the role of chance
Demographics and baseline characteristics were comparable between treatment groups. Patients had a mean age of 36.1 years and had been diagnosed for 5.25 years on average. Most patients (n = 42, 62.7%) had 2-4 lesions. No statistically significant changes in the sum of lesion sizes or PROs (Numerical Rating Scale, Biberoglu and Behrman Scale, and Endometriosis Health Profile-30) after treatment were noted, when compared to placebo. However, across all lesion types, a statistically significantly higher proportion of QVR patients than placebo patients demonstrated lesion regression of ≥ 65.0% volume (61.3% vs 35.5%, p = 0.042). In the DIE group, lesion regression occurred in more patients treated with QVR than those on placebo (36.8% vs 7.7%, p = 0.016). For diffusion imaging biomarkers, a significant difference in the diffusion coefficient standard deviation of DIE lesions (p = 0.039) was found in the QVR group compared to placebo. For perfusion imaging biomarkers, a statistically significant relationship with the treatment was identified in the endometrioma group for the 25th percentile of difference in fractional volume of extravascular extracellular space (mean difference −1.69, p = 0.009) from baseline. Incidence and severity of adverse events were similar between QVR and placebo.

Limitations, reasons for caution
MRI cannot currently detect superficial, highly vascularized endometriosis, which may be more responsive to QVR treatment than the more advanced stage of endometriosis (indicated by relatively large endometrioma and DIE) imaged in QLARITY. Moreover, 4 cycles may not be of sufficient duration for optimal treatment of these lesions.

Wider implications of the findings
QLARITY provides support for the use of MRI to diagnose and characterize changes in endometriotic/adenomyotic lesions. It is also the first MRI characterization of the placebo response in this population. Imaging biomarkers show promise in generating insights. QVR is safe and well tolerated; further studies of its efficacy are warranted.

Trial registration number
NCT03749109