E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000496 |
E.1.2 | Term | Acne |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the study is to evaluate the efficacy and the local and systemic
safety of 2% and 5% N-Acetyl-GED-0507-34-Levo gel, in comparison to the corresponding
vehicle gel, applied once daily (OD) for 12 weeks in patients with facial acne
vulgaris |
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E.2.2 | Secondary objectives of the trial |
The objective of the study is to evaluate the efficacy and the local and systemic
safety of 2% and 5% N-Acetyl-GED-0507-34-Levo gel, in comparison to the corresponding
vehicle gel, applied once daily (OD) for 12 weeks in patients with facial acne
vulgaris |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained. Written informed consent, before any study-related procedure, personally signed and dated by the patient if the patient is ≥ 18 years old, or signed and dated by the parent(s) or the legal guardian if the patient is ≥ 14 to < 18 years old. An additional informed assent form must be signed by patient if ≥ 14 to <18 years old to confirm his willingness to participate in the study. If the patient becomes 18 years of age during the study, the patient must provide written informed consent at that time to continue study participation.
2. Male and female patients aged ≥ 14 to ≤ 30 years old inclusive;
3. Diagnosis: Patients with facial acne vulgaris with an investigator’s global assessment (IGA) score of 3–4 at screening and baseline visits; 4. Inflammatory lesions: Patients with ≥ 20 and ≤ 100 inflammatory lesions (papules and pustules) on the face (excluding the nose) and ≤ 1 nodules;
5. Non-inflammatory lesions: Patients with ≥ 20 and ≤ 100 non-inflammatory lesions (open and closed comedones) on the face (excluding the nose);
6. Full comprehension: Patient’s and parent(s)/legal guardian for <18 years old patient’s ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study;
7. Women of childbearing potential* who are sexually active with a male partner must either be surgically sterile (hysterectomy or tubal ligation) or agree to use a reliable method of contraception with a failure rate of less than 1 % per year when used consistently and correctly such as:
•Hormonal oral, implantable, transdermal, or injectable contraceptives must be stable for at least 6 months before the screening visit
•A non-hormonal intrauterine device (IUD) must be started at least 2 months before the screening visit
•Sexual abstinence in accordance to the preferred life style or vasectomized partner** during the 12-week treatment period
*Note: According to Reccomendations related to contraception and pregnancy testing in clinical trials (CTFG, September 2014), a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 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 post-menopausal 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.
**Note: Provided that partner is the sole sexual partner of the female trial participant and has received medical assessment of the surgical success.
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E.4 | Principal exclusion criteria |
1.Patients with spontaneously improving or rapidly deteriorating acne within at least 3 months before study baseline. Patients who have a known history of acne unresponsive to topical and/or oral treatments. In particular subjects with history of persistent acne (a continuation of the disease from adolescence into adulthood) and subjects with history of relapsing acne. Patients with generalized or localized acne forms other than acne vulgaris, e.g., acne conglobata, acne fulminans, acne rosacea, secondary acne (chloracne, drug-induced acne, etc), nodule-cystic acne, acne tarda or acne requiring systemic treatment.
2.Patients who have a beard or who intend to grow a beard and/or to perform a facial tattoo during the study. Patient has facial hair or facial tattoos that could interfere with the study assessments in the opinion of the investigator.
3. Patients with other active skin diseases (e.g., urticaria, atopic dermatitis, sunburn, seborrheic dermatitis, perioral dermatitis, rosacea, skin malignancies) or active skin infections in the facial region (bacterial, fungal, or viral) or any other facial disease or condition that might interfere with the evaluation of acne or place the patient at unacceptable risk.
4. Known or suspected hypersensitivity to any active or inactive ingredient in the study products. Patients with a history of an allergic reaction or significant sensitivity to the formulations’ ingredients
5. Patients using, will use during the study, or discontinued less than 4 weeks before study baseline, prescribed or over-the-counter topical therapies for the treatment of acne including but not limited to: corticosteroids, antibiotics, azelaic acid, benzoyl peroxide salicylates, α-hydroxy/glycolic acid, any other topical cosmetic therapy for acne and retinoids on the face.
6. Patients using, will use during the study, or discontinued less than 4 weeks before study baseline, facial application of products containing glycolic or other acids, masks, washes or soaps containing benzoyl peroxide or salicylic acid, non-mild cleansers or moisturizers containing retinol, salicylic or alpha- or beta-hydroxy acids, facial procedures such as chemical peel, laser treatment, photodynamic therapy, acne surgery, cryodestruction or chemodestruction, x-ray therapy, intralesional steroids, dermabrasion, or depilation (except eyebrow shaping).
7. Patients using, will use during the study, or discontinued less than 12 weeks before study baseline, phototherapy for the treatment of acne including but not limited to: UV-A, UV-B, heliotherapy. Patients who have the need or plan to be exposed to artificial tanning devices or excessive sunlight during the study.
8. Patients using, will use during the study, or discontinued less than 12 weeks before study baseline, systemic therapies for the treatment of acne including but not limited to: antibiotics, isotretinoin. Other systemic therapy which, in the opinion of the investigator, could affect the patient’s acne (i.e., anabolics, lithium, EGRF inhibitors, iodides, systemic corticosteroids or other immunosuppressants).
9. Known systemic diseases that can lead to acneiform eruptions: a. Increased androgen production. 1) Adrenal origin: e.g., Cushing’s disease, 21-hydroxylase deficiency; 2) Ovarian origin: e.g., polycystic ovarian syndrome, ovarian hyperthecosis b. Cryptococcosis disseminated c. Dimorphic fungal infections.
10. Participation in the evaluation of any investigational product or device within 30 days before study baseline
11. Patient with underlying uncontrolled or unstable conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator could significantly compromise the patient’s safety and/or place the patient at an unacceptable risk. Any condition which in the investigator’s opinion would make it unsafe for the patient to participate in the study
12. History of alcohol or other substance abuse within one year before screening
13. Patient and parent(s)/legal guardian (if applicable) unable to communicate or cooperate with the investigator due to e.g., language problems, impaired cerebral function, bad mental conditions
14. Patient who may be unreliable for the study including patients who are unable to return for the scheduled visits.
15. Pregnant or breastfeeding women or planning to become pregnant during the study.
16.Affiliation with the investigator: Close affiliation with the investigator (e.g. a close relative) or persons working at the respective trial site or the subject is an employee of the sponsor; 17.Institutionalization: Subject is institutionalized because of legal or regulatory order.
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E.5 End points |
E.5.1 | Primary end point(s) |
Two primary efficacy endpoints: To demonstrate the efficacy of a 12 weeks treatment with 5% N-Acetyl-GED-0507-34-Levo gel, the following family of primary efficacy endpoints will be analyzed:
1. Endpoint 1 (E1): the percent change from baseline in total lesion count (inflammatory plus non-inflammatory) at V6/Wk12.
2. Endpoint 2 (E2): proportion of patients with an IGA success defined as score of “clear” (score = 0) or “almost clear” (score = 1) and at least a 2-score point reduction in IGA at V6/Wk12.
The assessment of E1 and E2 will be performed according to the hierarchical order above (chosen according to each endpoint clinical relevance), i.e. success on endpoint E1 will permit analysis of E2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
2. To demonstrate the efficacy of a 12 weeks treatment with both 2% and 5% N-Acetyl-
GED-0507-34-Levo on the following parameters: a. Absolute change from baseline in
total lesion count at V6/Wk12. b. Percent (%) change from baseline in inflammatory
lesion count at V6/W12. c. Percent (%) change from baseline in non-inflammatory lesion
count at V6/W12. d. Absolute change from baseline in inflammatory lesion count at
V6/Wk12. e. Absolute change from baseline in non-inflammatory lesion count at V6/Wk12.
f. Percent (%) change from baseline in total lesion count at each post-baseline visit.
g. Percent (%) change from baseline in inflammatory lesion count at the other postbaseline
assessment times. h. Percent (%) change from baseline in non-inflammatory
lesion count at the other post-baseline assessment times. i. Proportion of patients
with an IGA success defined as score of “clear” (score = 0) or “almost clear” (score =
1) and at least a 2-score point reduction in IGA at the other post-baseline assessment
times. j. Absolute change from baseline in total lesion count (inflammatory plus non-inflammatory)
at the other post-baseline visits. k. Absolute change from baseline in
inflammatory and non-inflammatory lesion count separately at the other post-baseline
assessments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
V6/W12 and the other post-baseline assessment times as described in details in E.5.2 section |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |