Efficacy and Safety Evaluation of AMY109 and Desogestrel in Women with Endometriosis: A Phase II Randomized, Double-Blind Clinical Trial

The primary objective of this study is to evaluate the **efficacy** of AMY109, both as a monotherapy and in combination with **desogestrel**, compared to desogestrel alone, in reducing disease severity in women with **endometriosis**. This assessment will be conducted through two methods: laparoscopic appearance and magnetic resonance imaging (MRI). The clinical relevance of this objective lies in determining the potential of AMY109, alone or in combination, to provide a more effective treatment option for endometriosis, a condition characterized by chronic pelvic pain and infertility, thereby improving patient outcomes and quality of life.

The clinical trial involves a total of **40 participants** who are exclusively female, aged between **18 and 49 years**. The study population is specifically selected to include women diagnosed with **endometriosis**, a chronic condition characterized by the presence of endometrial-like tissue outside the uterus. Participants were chosen based on their willingness to switch from their usual analgesics for dysmenorrhea, dyspareunia, and non-menstrual pelvic pain (NMPP) to those permitted by the study protocol. The trial includes women with moderate to severe endometriosis-associated NMPP and dysmenorrhea, as indicated by a numerical rating scale (NRS) score of 4 or higher during the screening period. The trial population is divided into two cohorts: a laparoscopy cohort in the UK and an imaging cohort in the EU. The laparoscopy cohort includes patients who have undergone a laparoscopic diagnosis within nine months prior to the screening period and are willing to undergo laparoscopic surgery post-treatment. The imaging cohort consists of patients with a clinical diagnosis of endometriosis confirmed by imaging assessments such as MRI, with at least one ovarian endometrioma identified. The trial does not include male participants, and the population is considered vulnerable due to the nature of the condition and the interventions involved.

The clinical trial is a **Phase II, randomized, double-blind** study designed to evaluate the efficacy and safety of **AMY109** in women diagnosed with **endometriosis**. The trial will compare the effects of AMY109 alone, AMY109 combined with **desogestrel**, and desogestrel alone. The study is structured to include a control group receiving a placebo. The trial is expected to commence recruitment in August 2024 and conclude by May 2028, with a total duration of approximately 52 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age and severity of endometriosis symptoms. The screening will involve clinical assessments, including imaging techniques like MRI, to confirm the presence of endometriotic nodules. Following successful screening, participants will be randomized into one of the treatment arms. The trial will include regular follow-up visits to monitor the participants' response to treatment and any adverse effects. These visits will occur at predetermined intervals throughout the study duration.

The end-of-study visit will mark the completion of the trial for each participant, during which final assessments will be conducted to evaluate the primary endpoint: changes in the revised American Society of Reproductive Medicine (r-ASRM) score or the size of endometriotic nodules as assessed by MRI. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or choose to withdraw consent. The trial's design ensures that all data collected will contribute to understanding the therapeutic potential of AMY109 in managing endometriosis.

The clinical trial involves the administration of **AMY109**, an investigational drug formulated as a **solution for injection**. The active substance, AMY109, is of protein origin and is administered via **intravenous infusion**. The dosing regimen for AMY109 is set at a maximum daily dose of 10 mg/kg, with a total maximum dose of 130 mg/kg over a treatment period of 52 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial.

**Desogestrel** is used as a comparator treatment in the study. It is provided in the form of **film-coated tablets** and contains the active substance desogestrel, a chemical compound. The oral administration of desogestrel is set at a maximum daily dose of 75 µg, with a total maximum dose of 27,300 µg over a 52-week treatment period. The tablets undergo over-encapsulation, repackaging, and labeling in accordance with Good Manufacturing Practices (GMP) to ensure consistency and compliance.

Additionally, a **placebo** is utilized to match AMY109, serving as a control in the study. The placebo is designed to mimic the appearance and administration route of AMY109, ensuring blinding of the study participants and investigators. The placebo does not contain any active pharmaceutical ingredients and is administered following the same schedule as AMY109.

**Tramadol Hydrochloride** is included as an auxiliary treatment. It is provided in **capsule** form and administered orally. The maximum daily dose is 300 mg, with a total maximum dose of 26,100 mg over a 29-day treatment period. Compliance with the dosing regimen is monitored to ensure adherence.

**Codeine Phosphate** is another auxiliary treatment, available in **tablet** form for oral administration. The maximum daily dose is 240 mg, with a total maximum dose of 208,800 mg over a 29-day treatment period. Participant adherence to the dosing schedule is closely monitored.

**Naproxen Sodium** and **Naproxen** are also used as auxiliary treatments. Naproxen Sodium is provided as a **film-coated tablet**, while Naproxen is available as a **gastro-resistant tablet**, both administered orally. The maximum daily doses are 1,100 mg and 1,000 mg, respectively, with total maximum doses of 957,000 mg and 870,000 mg over a 29-day treatment period. Compliance with the dosing regimen is ensured through regular monitoring.

**Paracetamol** is included as an auxiliary treatment in the form of **film-coated tablets** for oral administration. The maximum daily dose is 4,000 mg, with a total maximum dose of 3,480,000 mg over a 29-day treatment period. Participant adherence to the dosing schedule is monitored to ensure compliance.

**Ibuprofen** is another auxiliary treatment, provided as a **film-coated tablet** for oral administration. The maximum daily dose is 1,200 mg, with a total maximum dose of 2,088,000 mg over a 29-day treatment period. Compliance with the dosing regimen is monitored throughout the study.

The efficacy of the investigational product AMY109 in women with **endometriosis** will be assessed through a randomized, double-blind clinical trial. The primary endpoints for evaluating efficacy include changes in the total score and stage of the revised American Society of Reproductive Medicine (r-ASRM) score, assessed by laparoscopy, and changes in the sum of the long diameters of endometriotic nodules, assessed by magnetic resonance imaging (MRI). These assessments will be conducted from pre-treatment to post-treatment.

The trial will involve two cohorts: the laparoscopy cohort, which will be assessed in the UK, and the imaging cohort, assessed in the EU. The laparoscopy cohort will undergo surgical evaluation to determine changes in disease severity, while the imaging cohort will have MRI assessments to evaluate the size and presence of endometriotic nodules. The central readers will assess the MRI images to ensure consistency and accuracy in the evaluation of the nodules.

The trial is designed to compare the efficacy of AMY109 alone, AMY109 in combination with desogestrel, and desogestrel alone. The study will follow a structured schedule for measuring and collecting data, with assessments conducted at specified time points throughout the treatment period. The trial aims to provide comprehensive data on the efficacy of AMY109 in reducing disease severity in women with endometriosis.