Phase III/IV Multicenter Trial on Escalating Treatment of Scabies with Permethrin 5% and 10% Cream and Ivermectin Tablets

The primary objective of this clinical trial is to evaluate the **clinical efficacy** of treatment regimens for **scabies**. In stage I, the focus is on assessing the efficacy of the standard treatment with InfectoScab 5% cream, determining treatment success on day 14 for patients with a single application and on day 28 for those requiring a repeated application. In stage II, the efficacy of a higher concentration permethrin 10% cream is evaluated, with treatment success assessed on day 14 for patients in treatment arm A with one application, on day 28 for those with repeated applications, and on day 21 for patients in treatment arm B. This evaluation is clinically relevant as it aims to establish effective treatment protocols for scabies, a condition that can significantly impact quality of life.

Secondary objectives include:

• Effectiveness (therapy success) for various treatment stages and regimens.
• Frequency of required second treatments and the impact of prior antiscabial treatments.
• Assessment of itching using the Numerical Rating Scale and changes from baseline.
• Evaluation of the number and type of affected body regions.
• Proportion of patients with evidence of mites and use of non-trial-conforming antiscabiosa.
• Incidence of new scabies efflorescences and treatment failures.
• Analysis of adverse events, serious adverse events, and adverse drug reactions.
• Proportion of patients with reinfestation and cumulative efficacy of pure permethrin treatment.

The clinical trial focuses on evaluating the efficacy of treatments for **scabies**. The study population includes both male and female participants, with an age range from 6 to 85 years for stage I and from 2 to 85 years for stage II. The trial involves a vulnerable population, as it includes minors who require consent from legal guardians. Participants were selected based on confirmed acute scabies disease, verified through the detection of mites or mite larvae using microscopy. The sponsor has not provided information regarding the total number of participants. The trial population is required to have the investigational medication applied by trained specialist staff or, if not feasible, with the assistance of a third person to ensure proper application. No specific lifestyle considerations such as diet or physical activity are mentioned in the trial details.

The clinical trial is designed to evaluate the **efficacy** and safety of treatment regimens for **scabies** using permethrin-based therapies. This is a prospective, open-label, multicenter trial with an initial single-arm phase, followed by a randomized, three-arm phase if treatment failure occurs. The trial is structured in two stages: Stage I involves the application of InfectoScab 5% cream, while Stage II investigates higher-concentration permethrin cream regimens. The trial is expected to conclude by December 31, 2026, with participant recruitment having commenced on April 26, 2021.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility, which includes the detection of mites or mite larvae through microscopy. The inclusion criteria specify an age range of 6 to 85 years for Stage I and 2 to 85 years for Stage II, along with the requirement for informed consent. The trial involves multiple follow-up visits to assess treatment success, defined as the absence of mites and scabies symptoms, at specified intervals: day 14 or 28 for Stage I, and day 14, 21, or 28 for Stage II, depending on the treatment arm.

The expected duration of participant involvement varies based on the treatment response, with the maximum treatment period being four weeks. Participants may be withdrawn from the study if they experience adverse events, use non-conforming antiscabial treatments, or fail to adhere to the study protocol. The trial's primary endpoints focus on the efficacy of the permethrin treatments, while secondary endpoints include the frequency of required treatments, changes in itching severity, and the proportion of patients with new scabies lesions.

The clinical trial involves the use of **InfectoScab® 5% Crème**, a topical formulation containing the active substance **permethrin**. This medication is presented in a cream form and is intended for **cutaneous use**. The maximum daily dose is 60 grams, with a total maximum dose of 120 grams over a treatment period of up to 2 days. The cream is applied directly to the skin, and the treatment regimen may involve one or two applications depending on the patient's response. The product is manufactured by Infectopharm Arzneimittel und Consilium GmbH and is classified under the ATC code P03AC04.

Another treatment used in the trial is **DRIPONIN 3 mg Tabletten**, which contains the active substance **ivermectin**. This medication is available in tablet form and is administered **orally**. The dosing regimen is based on body weight, with a maximum daily dose of 200 micrograms per kilogram. The treatment period is limited to a single day. DRIPONIN is produced by Pädia GmbH and is categorized under the ATC code P02CF01. Compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol.

The trial also includes a higher concentration **permethrin cream** for escalated treatment regimens. This cream is used for **cutaneous application** and has a maximum daily dose of 60 grams, with a total maximum dose of 240 grams over a treatment period of up to 4 days. The cream is applied to the entire body, and the treatment may involve one or two applications depending on the study arm and patient response. This product is also manufactured by Infectopharm Arzneimittel und Consilium GmbH.

Throughout the trial, participant compliance with the treatment regimens is closely monitored to ensure accurate assessment of the clinical efficacy and safety of the treatments. The trial aims to evaluate the success of the treatments at specified intervals, with outcomes measured on days 14, 21, and 28, depending on the treatment arm and regimen.

The clinical trial aims to assess the efficacy of treatments for **scabies** using a structured approach across two stages. In Stage I, the primary endpoint is the clinical efficacy of the standard treatment with InfectoScab 5% cream, evaluated as treatment success on day 14 for patients receiving a single application, or on day 28 for those requiring a second application. Stage II involves assessing the efficacy of a higher-concentration permethrin 10% cream, with treatment success determined on day 14 or day 28 for patients in study arm A, and on day 21 for those in study arm B.

Secondary endpoints include the effectiveness of therapy, frequency of required second treatments, and changes in itching measured by the Numerical Rating Scale (NRS) from 0-10. The trial will also monitor the number and type of affected body regions, the proportion of patients with evidence of mites, and the use of non-trial-conforming antiscabiosa. Additionally, the trial will evaluate the proportion of patients with new scabies efflorescences and those with confirmed treatment failure, as well as adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs).

Efficacy assessments will be conducted through clinical evaluations at specified time points, including days 14, 21, and 28, depending on the treatment arm and stage. The trial will utilize reflected light microscopy or light microscopy of skin samples to confirm the presence of mites, nymphs, or larvae, ensuring accurate measurement of treatment outcomes. The trial is designed to provide comprehensive data on the efficacy and safety of escalating treatment regimens for scabies, contributing to improved therapeutic strategies for this condition.