E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to severe Acne conglobata in adults (ages 18 to 65 years, inclusive) |
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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 | 10000501 |
E.1.2 | Term | Acne conglobata |
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 primary objective of the study is to evaluate the proportion of subjects who achieve at least a 50% reduction in total number of inflammatory lesions at week 24 |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are
•To evaluate the IGA (Investigator’s Global Assessment) of acne severity •To evaluate the improvement of skin condition measured in SSRI (Symptoms Score Reduction Index) •To evaluate the effect of Apremilast in reduction of pain and itch of the inflammatory lesions measured by the visual analogue scale (VAS) of pain and itch •To evaluate lesion check, number of inflammatory lesions •Assessment of quality of life (QoL) by using DLQI •Assessment of depression profile by using PHQ9 •To evaluate compliance (drug accountability) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria •Diagnosis of acne conglobata for a minimum of 6 months •Active condition of acne conglobata •No clinical significant or severe abnormality of skin (e.g. scars, other severe skin disease) based on medical/medication history or physical examination as determined by the treating physician •Number of abscesses ≤ 2 •Minimum IGA of 2 (5-point scale) of severity of acne conglobata •Written informed consent obtained from the patients prior to the initiation of any protocol-required procedures •Compliance to study procedures and study protocol •Age 18 – 65 years
Main inclusion criteria related to prior treatments: •patients who do not tolerate or no longer tolerate therapies or for whom the following treatment options are contraindicated: oTopical retinoid therapy oIsotretionin and/or acitretin as standard therapy oTopical treatment with antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors osystemic antibiotics, systemic glucocorticoids osystemic retinoids
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E.4 | Principal exclusion criteria |
Main exclusion criteria •Previous use of Apremilast, or any other PDE-4 inhibitor.
Exclusion criteria related to IMP •According to SmPC •Known hypersensitivity to any component of the IMP •Current use of strong CYP3A4 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, and St. John’s Wort)
Exclusion criteria related to general health •Active dermatologic conditions which may confound the diagnosis of acne conglobata or would interfere with the assessment of treatment (e.g., acne inversa, atopic dermatitis, seborrheic dermatitis, ichtyosis, and psoriasis) •History of clinically significant infection within the last 4 weeks before screening, which, in the opinion of the treating physician, may compromise the safety of the patient •Presentation of special type of acne, including but not limited to: oMedication related acne (e.g., steroid abuse) oAcne with facial edema oRecalcitrant acne oAcne cosmetic, pomade acne oAcne mechanica oChloracne •History of any kind of cancer or carcinoma in situ within the last 5 years before screening •History of chronic alcohol/drug abuse within the last 12 months before screening •Pregnant or breastfeeding women •Females of childbearing potential not willing to use effective contraception (defined as PEARL index <1 - e.g. hormonal contraceptive containing estrogen and progesterone, or progesterone only, applied orally, intravaginal, transdermal or to be injected, IUD) for the duration of the study, strict abstinence, or partner had a vasectomy •Severe kidney insufficiency (GFR < 30 ml/min) •Any severe disease, which, in the opinion of the treating physician, may interfere or worsen the acne conglobata or could become a safety problem for patients •History of or current Hepatitis-B, Hepatitis-C or HIV infection •Any active medication which suppresses the immune system, including disease modifying anti-rheumatic drugs (DMARDs) •Current participation in another investigational clinical trial or participation in another investigational clinical trial within 30 days prior to screening •Major surgery within the last 4 weeks before screening •Subject susceptible to take a local corticosteroid treatment (class I – III) during the study except inhaled or topic when needed to treat a condition outside the treatment area (head, neck, upper trunk)
Exclusion criteria related to prior treatments: •Washout times for previous therapy for acne conglobata before screening: o1 week for any topical treatment (e.g., antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors) o4 weeks for any systemic antibiotics, systemic glucocorticoids or UV-therapy o12 weeks for any systemic retinoids or any investigational drug oPatients who take any kind of contraceptive therapy (eg. estrogene, gestagene) with known positive effect on acne must be on stable dosage for a minimum of 6 month
Exclusion criteria related to formal aspects: •Underage or incapable patients •Patients who are legally institutionalized |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy: •Determination of proportion of subjects who achieve at least a 50% reduction in total number of inflammatory lesions at week 24 compared to baseline
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy: •At week 24 compared to baseline
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E.5.2 | Secondary end point(s) |
Secondary efficacy: Determination of •the proportion of subjects who achieve an IGA 0 / 1 or an improvement of a minimum 2 points on an IGA 5-point scale •change in skin condition measured in SSRI •change in pain and itch of the inflammatory lesions measured by a VAS •change in quality of life measured by DLQI •change in depression profile measured by PHQ-9 •change in compliance (drug accountability) as indicated in flow chart.
Overall safety parameters: •Frequency and seriousness of adverse events (AEs) (as detailed under Protocol Version 2.0 dated 20. May 2019)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The entire assessments will be done on week 0 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5), week 16 (visit 6) and week 24 (visit 7).
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |