Efficacy and Safety Evaluation of Topical Alanyl Glutamine (MC2-25) in Women with Vulvar Lichen Sclerosus: A Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2023-503516-32-00
Protocol: MC2-25-C3
Sponsor: Mc2 Therapeutics Limited

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Diseases & Conditions

Lichen sclerosus

Objectives

The primary objective of this clinical trial is to evaluate the **efficacy** of MC2-25 cream compared to the MC2-25 vehicle in women diagnosed with **vulvar lichen sclerosus** (VLS). This objective is clinically relevant as it aims to determine the therapeutic potential of MC2-25 cream in alleviating the symptoms associated with VLS, a chronic inflammatory skin condition affecting the vulvar area, which can significantly impact the quality of life.

Secondary objectives include:

Exploring the **safety** of MC2-25 cream compared to the MC2-25 vehicle in VLS, which is crucial for assessing the risk-benefit profile of the treatment.
Investigating the burden of VLS on women's lives, providing insights into the broader impact of the condition beyond clinical symptoms.

Participants

The clinical trial focuses on evaluating the efficacy of MC2-25 cream in treating **vulvar lichen sclerosus** (VLS). The study population comprises exclusively female participants, aged 18 years and older, who have been clinically diagnosed with VLS by a dermatologist or gynecologist. Participants must have experienced symptoms such as itching or pain for at least six months prior to the baseline visit. The trial includes women of both childbearing and non-childbearing potential, with specific requirements for contraception and pregnancy testing for those of childbearing potential. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on the presence of specific clinical signs of VLS, such as hyperkeratosis or sclerosis, in designated vulvar areas. Participants are required to have documented moderate itch levels, as measured by the WI-NRS scores, to ensure consistent symptom severity at baseline. The study does not include male subjects and involves a vulnerable population, emphasizing the need for careful ethical considerations in the trial's conduct.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of MC2-25 cream compared to its vehicle in women diagnosed with **vulvar lichen sclerosus** (VLS). The trial will span a duration of 12 weeks, with the primary objective being to assess the mean change in the weekly mean Worst Itch Numeric Rating Score (WI-NRS) from baseline to week 12. Secondary endpoints include changes in the Worst Pain Numeric Rating Score (WP-NRS) and improvements in Skindex-29 domains.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis of VLS, and the presence of specific symptoms. Following the screening, participants will be randomized to receive either the MC2-25 cream or the vehicle. Study visits will occur at baseline, followed by regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the trial, where final assessments will be conducted.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with trial procedures. Participants are required to adhere to the trial protocol, including the use of effective contraception for women of childbearing potential, and to maintain accurate diary entries for symptom assessment. The trial is not classified as a low-intervention study and is conducted under phase IV, ensuring rigorous evaluation of the investigational product's therapeutic potential.

Treatment

The clinical trial involves the evaluation of **MC2-25 cream**, an experimental medication formulated as a topical cream. The active ingredient in this formulation is **alanyl glutamine**, a compound categorized under the origin of "Protein - Other." The cream is intended for topical application, with a maximum daily dose of 12 applications per day. The total maximum dose over the treatment period is 1008 applications, with the treatment duration extending up to 12 weeks. The cream is manufactured by MC2 Therapeutics Ltd and is not a pediatric formulation. The primary objective of the trial is to assess the efficacy and safety of MC2-25 cream in women diagnosed with vulvar lichen sclerosus (VLS).

The study also includes a comparator treatment, referred to as the **MC2-25 vehicle**, which serves as a placebo. This vehicle is identical to the test product in formulation but lacks the active substance, alanyl glutamine. The vehicle is used to ensure the double-blind nature of the trial, allowing for an unbiased comparison of the therapeutic effects of the active cream versus the placebo. The vehicle is applied topically in the same manner and frequency as the MC2-25 cream, ensuring consistency in administration across both study arms.

Efficacy

The efficacy of the investigational product, MC2-25 cream, in the treatment of vulvar lichen sclerosus (VLS) will be assessed through a series of predefined endpoints. The primary endpoint is the mean change in the weekly mean **Worst Itch Numeric Rating Score (WI-NRS)**, as recorded in the patient's diary, from Baseline to Week 12. This will be compared between the MC2-25 cream and the MC2-25 vehicle. Secondary endpoints include the mean change in the weekly mean **Worst Pain Numeric Rating Score (WP-NRS)** over the same period, as well as the percentage of patients achieving a ≥4-point and ≥3-point improvement in both WI-NRS and WP-NRS. Additionally, changes in Skindex-29 domains from baseline to week 12 will be evaluated.

Data collection will involve patient-reported outcomes, specifically the WI-NRS and WP-NRS, which patients will record in their diaries. These scores will be collected weekly and analyzed to determine the efficacy of the treatment. The trial is designed as a parallel group, randomized, double-blind study over a 12-week period, ensuring that the data collected is robust and reliable. The analysis will focus on comparing the efficacy of the MC2-25 cream against the vehicle, providing insights into its potential benefits for patients with VLS.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Women, of any race or ethnicity, who are ≥18 years of age at the time of Screening 1.
Able to understand the trial and willing to comply with trial requirements.
Has provided written informed consent.
Clinical diagnosis of VLS made by either a dermatologist or a gynaecologist familiar with VLS.
Presence of at least one of the following signs of VLS: a. Hyperkeratosis (i.e., patches/plaques of bright white skin with a ‘powdery’ texture) and/or b. Sclerosis (i.e., areas of yellowish/ivory white skin with a smooth/waxy/firm texture. Sclerosis is often seen at the tips of the labia minora, or on periclitoral or perineal skin) in at least one of the following vulvar areas: Clitoris and/or periclitoral skin (C); Right interlabial sulcus and labium minus (R); Left interlabial sulcus and labium minus (L); Posterior Fourchette and/or perineum (P)
First symptoms of VLS (e.g., itching and/or pain) noticed by the patient at least 6 months before baseline.
At least four WI-NRS scores available in the diary for calculation of the average WI-NRS at the baseline visit.
At least moderate itch defined as average WI-NRS ≥4 at the Baseline visit (average WI-NRS is calculated as the average of all available and at least four WI-NRS scores which are to be reported once daily by the patient in the diary for 7 days prior to the Baseline visit
Women must be of either: a) Non-childbearing potential, i.e., post-menopausal* or confirmed sterile (e.g., hysterectomy, bilateral salpingectomy or bilateral oophorectomy) (*Note: a postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient) OR, b) Childbearing potential with a negative highly sensitive* urine pregnancy test at the Baseline visit (*Note: a highly sensitive urine pregnancy test must have a sensitivity down to at least 25 mIU/ml for human chorionic gonadotropin (hCG)).
Women of childbearing potential must agree to use a highly effective method of contraception (i.e., a method with a failure rate of less than 1 % per year when used consistently and correctly) while receiving double-blind treatment.

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Exclusion Criteria

Pregnant, breast feeding, or planning to become pregnant during the trial.
Any (other than VLS) ongoing localised or systemic disease involving the vulvar region – e.g., lichen planus, psoriasis, eczema, ulcerative colitis or known active infection (bacterial, viral or fungal).
Ongoing symptomatic Urinary Tract Infection (UTI).
Ongoing or prior diagnosis of any genitoanal malignancy or pre-malignancy
Any kind of ongoing cancer (or anti-cancer treatment within 3 months or 5 half-lives (whichever is longest) prior to the Baseline visit).
Any chronic or acute systemic medical condition that, in the opinion of the investigator, may pose a risk to the safety of the patient or may interfere with the assessment of efficacy in this trial.
Known history of allergic reaction to any ingredients in MC2-25 cream or MC2-25 vehicle
Start of a new or change of existing non-biologic systemic treatment, including but not limited to corticosteroids, cyclosporin, methotrexate and tacrolimus, within 21 days prior to the Baseline visit.
Start of a new or change of existing biologic systemic treatment, including but not limited to etanercept, adalimumab, alefacept, infliximab, and ustekinumab within 3 months or 5 half-lives (whichever is longest) prior to the Baseline visit.
Start of a new or change of existing systemic or intravaginal treatment with estrogen containing products, within 21 days prior to the Baseline visit
Start of new or change of menstrual care routines within 21 days prior to the Baseline visit.
Use of emollients (including but not limited to creams, ointments, oils, or soaps with emollient properties) on the vulvar region within 3 days prior to the Baseline visit.
Use of any topical treatment on the vulvar region, including but not limited to calcineurin inhibitors, corticosteroids or anti-infectives within 14 days prior to the Baseline visit.
Use of any light therapy on the vulvar region, including but not limited to UV-B, UV-A, and laser, within 28 days prior to the Baseline visit.
Received a non-marketed or blinded drug within 28 days or 5 half-lives (whichever is longer) prior to the Baseline visit.
If in the opinion of the investigator, the patient is unlikely to comply with the clinical trial protocol.
Previously randomised in this trial.