Comparative Efficacy and Safety of Ivermectin 10 mg/g Cream Versus Vehicle in Patients with Papulopustular Rosacea: A Randomized, Double-Blind Study
- Trial ID
- 2023-505897-13-00
- Protocol
- 23-03/Iver-C
- Sponsor
- Dermapharm AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this double-blind, randomized clinical study is to compare the **efficacy** of Ivermectin cream (10 mg/g) versus Soolantra® 10 mg/g cream and a vehicle in reducing inflammatory lesions in patients with **papulopustular rosacea** at Day 84 ± 4. This is clinically relevant as it aims to establish the most effective treatment option for reducing the inflammatory lesions associated with this chronic skin condition, potentially improving patient outcomes and quality of life.
Secondary objectives include:
- Comparing the efficacy of Ivermectin cream versus Soolantra® cream and vehicle in achieving a clinical response of "success" at Day 84 ± 4.
- Evaluating the reduction of inflammatory lesions at all other time points.
- Assessing the reduction of facial erythema at all time points.
- Examining changes in the Investigator's Global Assessment (IGA).
- Determining the overall therapeutic success.
- Comparing the safety profiles of the treatments.
- Assessing the tolerability of the treatments.
Participants
The clinical trial involves participants diagnosed with **papulopustular rosacea**, a condition characterized by inflammatory lesions on the face. The study population includes both women and men aged 18 years and older. Participants are required to have between 15 and 50 inflammatory lesions, with no more than 2 nodular lesions, and must have a moderate to severe grade of rosacea as assessed by the Investigator's Global Assessment. The trial includes both male and female subjects, with specific considerations for female participants of childbearing potential, who must use a highly efficient contraceptive method and have a negative high-sensitivity urine pregnancy test prior to the study. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on the diagnosis of papulopustular rosacea and the presence of specific lesion criteria. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating additional ethical considerations in the study design.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, and controlled study to evaluate the efficacy and safety of **Ivermectin** 10 mg/g cream compared to Soolantra® 10 mg/g cream and a vehicle in patients with **papulopustular rosacea**. The primary objective is to assess the reduction in inflammatory lesions over a period of 84 days, with the primary endpoint being the percent change in lesion count from baseline to the end of treatment. Secondary endpoints include the proportion of subjects achieving a clinical response, changes in lesion count and facial erythema, and the incidence of adverse events.
The trial will commence with a screening visit to confirm eligibility based on inclusion criteria such as age, diagnosis, and lesion count. Participants will be required to provide written consent and, for females of childbearing potential, a negative pregnancy test. The study will involve multiple follow-up visits to monitor progress and assess endpoints, with visits scheduled at regular intervals throughout the 12-week treatment period. The end-of-study visit will evaluate the overall therapeutic success and tolerability of the treatment.
Participants are expected to be involved in the study for approximately 12 weeks, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or adverse events that necessitate discontinuation. The trial is anticipated to start recruitment in September 2024 and conclude by September 2027, ensuring a comprehensive evaluation of the investigational product's efficacy and safety in the target population.
Treatment
The clinical trial involves the use of three treatments to evaluate their efficacy and safety in patients with **papulopustular rosacea**. The first treatment is the experimental medication, **Ivermectin Cream**, which contains the active substance ivermectin at a concentration of 10 mg/g. This cream is manufactured by Dermapharm AG and is intended for **cutaneous use**. The pharmaceutical form of the product is a cream, and it is administered topically. The maximum daily dose is 2.14 grams, with a total maximum dose of 180 grams over a treatment period of up to 12 weeks. The cream is of chemical origin and is not a paediatric formulation.
The second treatment is the comparator, **Soolantra 10 mg/g Creme**, which also contains ivermectin as the active ingredient at the same concentration of 10 mg/g. This product is manufactured by Galderma Laboratorium GmbH and is similarly intended for cutaneous use. The pharmaceutical form is a cream, and it is applied topically. The dosing schedule is identical to that of the Ivermectin Cream, with a maximum daily dose of 2.14 grams and a total maximum dose of 180 grams over a 12-week period. This product is also of chemical origin and is not formulated for paediatric use.
The third treatment is a **Vehicle to Test Product**, which serves as a placebo in this study. The vehicle is used to match the appearance and application method of the active treatments but does not contain the active substance ivermectin. The pharmaceutical form and route of administration are not specified, but it is implied to be similar to the other treatments for consistency in the trial. The vehicle is used to assess the efficacy of the active treatments by providing a baseline for comparison.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the reduction of inflammatory lesions in patients with **papulopustular rosacea**. The primary endpoint is the percent change from baseline to the end of treatment (Visit 8) in the count of inflammatory lesions, specifically papules and pustules. Secondary endpoints include the proportion of subjects achieving a clinical response of "success," defined as an Investigator's Global Assessment (IGA) score of "0 = Clear" or "1 = Almost Clear" at Day 84 ± 4. Additionally, the percent and absolute change in inflammatory lesion count will be measured at various visits, including Visit 2 through Visit 7, compared to baseline (Visit 1).
Further secondary endpoints involve the change in facial erythema and the IGA score from baseline to subsequent visits, as well as the evaluation of overall therapeutic success by both the investigator and the patient at the end of treatment. The incidence of adverse events and the tolerability of the treatment will also be assessed from Visit 2 to Visit 8. These efficacy parameters will be collected and analyzed at specified timepoints throughout the study to determine the comparative efficacy of Ivermectin 10 mg/g Cream, Soolantra® 10 mg/g Cream, and the vehicle in reducing inflammatory lesions associated with papulopustular rosacea.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Women and men ≥ 18 years of age
- Written consent to study participation after patient information by the investigator
- Diagnosis of papulopustular rosacea according to generally accepted criteria
- On the face, ≥ 15 and not more than 50 inflammatory lesions (e.g. papules and pustules), thereof ≤ 2 nodular lesions
- Investigator`s Global Assessment (IGA) of rosacea severity grade 3 (moderate) or 4 (severe)
- For all female patients of childbearing potential: Application of an established highly efficient contraceptive method during the whole study
- For all female patients of childbearing potential: Urine pregnancy test with negative result prior to study start. The urine pregnancy test used must have a sensitivity down to at least 25 mIU/ml for human chorionic gonadotrophin (hCG) (High sensitivity pregnancy test)
Exclusion Criteria
- Presence of other forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin) or other dermatoses that may be confounded with papulopustular rosacea, such as perioral dermatitis, facial keratosis pilaris, seborrheic dermatitis and acne
- Other concomitant diseases which may - taking the present knowledge into account - influence the parameters evaluated in the study in a way that an objective evaluation would be impossible
- Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of rosacea
- Known intolerance or hypersensitivity against ivermectin or any of the other ingredients in the study medication
- Use within 6 months prior to baseline of oral retinoids (e.g. isotretinoine) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed)
- Use within 30 days prior baseline or during the study of topical facial treatment with retinoids, benzoyl peroxide, antibiotics, corticosteroids, immunomodulators (like e.g. tacrolimus), or other topical rosacea treatment (e.g. azelaic acid, metronidazole, brimonidine, oxymetazoline)
- Use within 30 days prior to baseline of systemic antibiotics known to have an impact on the severity of facial rosacea (like e.g. tetracycline and its derivatives doxycyclin or minocyclin, macrolides (like erythromycine, clarithromycine, azithromycine), or systemic corticosteroids
- Exposure to excessive UV radiation within two weeks prior baseline, or the subject is planning exposure during the study (e.g. occupational exposure to the sun, planned holidays in the sun during the study, phototherapy, tanning salon)
- Subjects with moderate or severe rhinophyma, dense telangiectases, or plaque-like facial edema, or ocular rosacea (e.g., conjunctivitis, blepharitis, or keratitis) of sufficient severity to require topical or systemic treatment
- Other severe acute or chronic concomitant disease with severe impairment of the general condition
- Other concomitant medication which may - taking the present knowledge into account - influence the methods of measurement used in this study or the resulting data
- Reasonable doubt concerning the co-operation of the patient
- Participation in another clinical study within the last 30 days prior to inclusion in this study
- Participation in this study at an earlier date
- Women with existing or intended pregnancy or during lactation
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 02 Sept 2024 | 726 |
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 |
|---|---|---|---|---|---|---|
Vehicle to Test Product | Placebo | N/A | — | — | — | N/A |
Ivermectin Cream | Test | CREAM | CUTANEOUS USE | 2.14 | 12 | PRD11157645 |
Soolantra 10 mg/g Creme | Comparator | CREME | CUTANEOUS USE | 2.14 | 12 | PRD2838920 |