A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Adaptive Phase 3 Study to Evaluate the Efficacy and Safety of Sinecatechins (Defined Extract of Green Tea Leaves) Ointment in Adult Patients with Actinic Keratosis of the Scalp and the Face.
- Trial ID
- 2022-502811-12-00
- Protocol
- Pro_VER-01-21_AR
- Sponsor
- Aresus Pharma GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **superiority** of Veregen® 10% ointment over placebo in achieving complete (100%) clearance of a pre-defined treatment area (TA) in patients with **Actinic Keratosis** (AK) of the scalp and/or face. This is assessed following a 12-week treatment period and a subsequent 4-week post-treatment period, totaling a maximum of 16 weeks for patients who do not achieve complete clearance by the end of the treatment period. The clinical relevance of this objective lies in its potential to establish an effective topical treatment option for AK, a condition that can progress to squamous cell carcinoma if left untreated.
Secondary objectives include: - Evaluating the efficacy of Veregen® 10% ointment compared to placebo by measuring clinical clearance, lesion count, AK severity grading, and assessment of erythema and thickness of individual AK lesions in the TA. - Assessing the recurrence of AK in the TA at any timepoint after complete clinical clearance until the end of the post-treatment follow-up. - Evaluating the safety profile of the treatment through adverse event (AE) and serious adverse event (SAE) recording, local skin reactions, and tolerability assessments. - Determining the incidence of squamous cell carcinoma (SCC) in the TA and on the head during the study. - Evaluating patient satisfaction with Veregen® 10% ointment treatment compared to placebo.
Participants
The clinical trial focuses on individuals diagnosed with **Actinic Keratosis** (AK) of the scalp and/or face. The study population includes both male and female participants aged 18 years and older. Participants are required to have a clinically confirmed diagnosis of mild to moderate AK, with at least 4 but not more than 8 isolated lesions in a contiguous treatment area of 25 square centimeters on the face or bald scalp. The lesions must be typical AK lesions of Olsen grade I or II. The trial population was selected based on their willingness to participate and ability to follow study instructions, as well as their likelihood to complete all study requirements. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations may be in place to ensure participant safety and ethical conduct throughout the study.
Plans and Procedures
The clinical trial is designed as a **randomized**, **placebo-controlled**, **double-blind**, adaptive Phase 3 study to evaluate the efficacy and safety of a sinecatechins ointment, a defined extract of **green tea** leaves, in adult patients with **actinic keratosis** of the scalp and face. The trial aims to demonstrate the superiority of Veregen 10% ointment over a placebo by achieving complete clearance of a predefined treatment area following a 12-week treatment period and a 4-week post-treatment period. The study is expected to conclude by March 31, 2026, with recruitment starting on October 2, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of mild to moderate actinic keratosis, and the presence of 4 to 8 isolated lesions in a contiguous treatment area. The treatment period includes on-site visits at 2, 4, 8, and 12 weeks, during which the primary endpoint of complete clinical clearance will be assessed. A 4-week post-treatment visit will follow for those without complete clearance at the end of treatment. The study also includes a 1-year post-treatment follow-up period with visits at 8 weeks post-treatment, and at 3, 6, 9, and 12 months post-treatment to monitor long-term efficacy and safety.
Participant involvement is expected to last up to 16 weeks for the treatment and post-treatment phases, with an additional 12 months for follow-up. Conditions that may lead to early termination from the study include withdrawal of consent, non-compliance with study procedures, or the occurrence of adverse events that, in the investigator's opinion, warrant discontinuation. The study will assess both efficacy endpoints, such as lesion clearance and severity grading, and safety endpoints, including adverse events and local skin reactions, throughout the trial duration.
Treatment
The clinical trial involves the use of **Veregen 10% Ointment**, which contains the active substance **Camellia sinensis (green tea) leaf extract**. This experimental medication is formulated as an ointment and is intended for **topical use**. The maximum daily dose is 750 mg, with a total maximum dose of 63,000 mg over the treatment period. The treatment is administered over a period of 12 weeks, with a subsequent 4-week post-treatment observation period. The ointment is applied directly to the affected area on the scalp and face, targeting **actinic keratosis**. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.
The study also includes a **placebo** comparator, which is designed to match the **Veregen 10% Ointment** in color, texture, and packaging. The placebo is a brown, smooth ointment free from gritty particles, ensuring that it is indistinguishable from the active treatment in appearance. This placebo is used to maintain the double-blind nature of the trial, allowing for an unbiased assessment of the efficacy and safety of the experimental medication. Participants are randomly assigned to receive either the active treatment or the placebo, and the administration follows the same schedule and route as the active ointment.
Efficacy
The efficacy of the investigational product, Veregen® 10% ointment, will be assessed in a multicenter, randomized, placebo-controlled, double-blind, adaptive Phase 3 study. The primary endpoint for evaluating efficacy is the complete clinical clearance of the treatment area (TA) following a 12-week treatment period and a 4-week post-treatment (PT) period. Complete clinical clearance is defined as the total disappearance of all clinically visible and/or palpable **actinic keratosis** (AK) lesions in the TA, resulting in a total number of AK lesions (TN) equal to zero.
Secondary efficacy endpoints include the assessment of clinical clearance at various time points during the treatment and post-treatment follow-up periods. These include complete clinical clearance at every on-site visit during the treatment period (at 2, 4, 8, and 12 weeks) and at 4 weeks PT, as well as the time to complete clinical clearance. Additionally, at least 75% clinical clearance of the TA will be evaluated at each on-site visit, defined as a 75% reduction in the number of AK lesions compared to baseline. Lesion count and AK severity grading will also be measured, with assessments of the total number of AK lesions, the number of new lesions, and the severity of AK according to Olsen and modified Stockfleth criteria.
Data collection will occur at specified intervals throughout the study, including during a 1-year post-treatment follow-up (PTFU) period, with visits at 8 weeks PT, and at 3, 6, 9, and 12 months PT. The recurrence of AK lesions will be monitored, including the proportion of patients with recurrence and the extent and time to recurrence. Efficacy assessments will be conducted using validated clinical scales and methods to ensure accurate and reliable data collection and analysis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients willing to participate, obtained written informed consent.
- Male or female patients ≥ 18 years.
- Clinically confirmed diagnosis of mild to moderate Actinic keratosis (AK) of the face including the forehead (excluding eyelids, lips and mucosa) and/or the bald scalp.
- Presence of at least 4 but not more than 8 isolated (i.e. discrete and quantifiable) AK lesions located in a contiguous treatment area (TA) on the face and/or bald scalp of 25 square-cm.
- AK lesions of the TA must be clinically typical AK lesions of Olsen grade I and/or grade Olsen grade II.
- Ability to follow study instructions and likely to complete all study requirements.
Exclusion Criteria
- TA is within 5 cm of an incompletely healed wound or infected area of the skin.
- AK lesions in the TA with atypical clinical appearance (e.g. TA contains massively hyperkeratotic and hypertrohic lesions (Olsen grade III AK), recalcitrant lesions, cutaneous horns, and/or lesions that had not responded to 2 previous cryotherapies).
- Within the TA, any suspicion of other malignant or benign skin tumors.
- History of a genetic skin-cancer disorder (e.g. xeroderma pigmentosum) and/or invasive tumor in the TA, such as a Merkel cell tumor, an invasive spinocellular carcinoma or a BCC (Basal Cell Carcinoma) and/or any skin cancer (suspected or diagnosed recently or within 5 years ago before screening).
- History or evidence of skin conditions other than AK that would interfere with evaluation of the study medication (e.g. eczema, unstable psoriasis).
- Patients having any significant physical abnormalities in the TA that may cause difficulty with examination or AK assessments (e.g. tattoes, scars, hyperpigmentation, etc.).
- Evidence of clinically significant or unstable medical conditions such as: (a) metastatic tumor or tumor with high probability of metastatic spread, (b) heart failure (NYHA class III or higher), (c) immunosuppressive disorder (e.g. HIV, organ transplant patients), (d) hematologic, hepatic, renal, neurologic or endocrine disorder, (e) collagen-vascular disorder (e.g. cerebro-vascular or other bleeding disorder), (f) gastrointestinal disorder (e.g. active ulcera or history of recurrent peptic ulcera or hemorrhage).
- Patients not willing to stop using skin care products (e.g. self-tanning products, sunscreens, make-ups/colored day care cremes, topical treatments with anti-aging products, vitamin A, vitamin C, and/or vitamin E containing ointments and gels) in the TA during the interventional period of the study (i.e., during the treatment and until 4 weeks post-treatment).
- Patients not willing to stop any use of make-ups colored day care cremes, and sunscreens in the treatment area within 12 hours prior to an on-site visit during the PTFU period.
- Patients not willing to abstain from sunbathing (including solarium) or any outdoor activities with intensive sun exposure without taking appropriate measures to protect the treatment areas during the study.
- Patients with a tendency to manipulate skin parts e.g. scratching.
- Pregnant or breast-feeding patients.
- Patients currently or within the past 4 weeks participating in another clinical study.
- Any previous randomization into this clinical study.
- Any suspicion of current drug and/or alcohol abuse.
- Patient is institutionalized because of legal or regulatory order.
- Dependency (as an employee or relative) to the sponsor/responsible CRO or investigator.
- Any condition that in the opinion of the investigator can influence the evaluation of the treatment, and other assessments.
- Hypersensitivity, intolerance or allergies against ingredients of Veregen® 10% ointment and/or Placebo ointment.
- Have received the following topical or physical treatments for any indication in the treatment area within the designated time period before treatment with study drug: a) Curettage, Photodynamic therapy, Topical inhibitors of Src tyrosine kinase signaling and tubulin polymerization (e.g.,Tirbanibulin) for/in a period of 12 weeks; b) Topical retinoids, Topical diclofenac preparations, Topical 5-fluorouracil preparations, Topical immunomodulators (e.g., Imiquimod) for/in a period of 6 weeks; c) Topical steroids, Cryo-, thermo- or chemodestruction, Surgical excision for/in a period of 4 weeks.
- Initiation of treatment with the following systemic treatments for any indication within 2 weeks before Baseline: Immunomodulators or immunosuppressive therapies, Diclofenac, Corticosteroids (oral or injectable), Inhaled corticosteroids (>1200 µg/day for beclomethasone, or >600 µg/day for fluticasone)
- Current or planned intake of high dosed oral green tea preparations for any reason
- Current or planned application of dermal preparations with astringent effect on the TA, such as zinc paste or tannin-containing ointments/creams
- Patients taking a drug with known potential for skin reactions must have taken it at a stable dose for at least 2 weeks prior to Baseline, except in cases where no previous skin reactions have occurred at any dose.
- Women of childbearing potential (WOCBP) will not be considered unless they use a highly effective method of contraception (failure rate of less than 1% per year) during the interventional period until 4-weeks PT (EoI, V9).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 02 Oct 2023 | 280 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Veregen 10% Salbe | Test | SALBE | TOPICAL USE | 750 | 12 | PRD7622589 |
Placebo to Veregen® 10% Ointment: it is a brown, smooth ointment, free from gritty particles manufactured to match the verum ointment in colour, amount of material in the primary container and appearance. | Placebo | N/A | — | — | — | N/A |