Clinical trial NCT04161456: Preliminary Efficacy and Safety of Apremilast in the Treatment of Acne Conglobata
Official title: Preliminary Efficacy and Safety of Apremilast in the Treatment of Acne Conglobata: A Phase II, Single Centre, Open Label, Proof of Concept Study for the Treatment of Acne Conglobata With the PDE-4 Inhibitor Apremilast (APACCO-Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acne Conglobata
Keywords: Acne conglobata
Phosphodiesterase (PDE)-Inhibitor
Lead sponsor: Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
Sponsor class: OTHER
Collaborators: name: Dermatology Department University Hospital Frankfurt
name: Celgene
First posted: 2019-11-13
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients will be treated with Apremilast
Primary purpose: TREATMENT

Brief summary: Apremilast mediates its clinical effect through the cAMP-PKA-NFkappaB pathway which results in a clinical picture changes to a decrease of all signs of inflammation.

Due to the NFkappaB mediated chronical inflammation in the pathogenesis of acne conglobata, a treatment with Apremilast seems to be an effective option.

In this study, treatment with Apremilast (Otezla®) will be performed in patients with acne conglobata to observe its preliminary efficacy and safety in an open label, single-centre proof of concept study design.

Detailed description: Treatment options for acne conglobata are limited and those which are effective can only be used in short term such as systemic steroids, antibiotics or retinoids due to their association to side effects or potentially teratogenetic effects.

Apremilast, a specific inhibitor for PDE-4, mediates its clinical effect through the cAMP-PKA-NFkappaB pathway which results in a decrease of pro-inflammatory and increase of anti-inflammatory cytokines in several types of leukocytes. The clinical picture changes to a decrease of all signs of inflammation.

Due to the NFkappaB mediated chronical inflammation in the pathogenesis of acne conglobata, a treatment with Apremilast seems to be an effective option.

In this study, treatment with Apremilast (Otezla®) will be performed in patients with acne conglobata to observe its preliminary efficacy and safety in an open label, single-centre proof of concept study design.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acne conglobata for a minimum of 6 months
* Active condition of acne conglobata, defined as minimum IGA of 2 (5-point scale) of severity of acne conglobate
* 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
* 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
* patients who do not tolerate or no longer tolerate therapies or for whom the following treatment options are contraindicated:

  * Topical retinoid therapy
  * isotretinoin and/or acitretin as standard therapy
  * Topical treatment with antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors
  * systemic antibiotics, systemic glucocorticoids
  * systemic retinoids

Exclusion Criteria:

* Previous use of Apremilast, or any other PDE-4 inhibitor
* According to Summary of Product characteristics (SmPC); see special warnings regarding suicidal ideation and behaviour
* Known hypersensitivity to any component of the investigator medicinal product (IMP)
* Current use of strong CYP3A4 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, and St. John's Wort) 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, ichthyosis, 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:

  * Medication related acne (e.g., steroid abuse)
  * Acne with facial edema
  * Recalcitrant acne
  * Acne cosmetic, pomade acne
  * Acne mechanica
  * Chloracne
* 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 including also strict abstinence, or partner had a vasectomy
* Severe kidney insufficiency (glomerular filtration rate (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) and biologicals
* Current participation in another investigational clinical trial or participation 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)
* History and current status of suicidal thoughts or behaviour or previous suicidal attempt
* Washout times for previous therapy for acne conglobata before screening:

  * 1 week for any topical treatment (e.g., antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors)
  * 4 weeks for any systemic antibiotics, systemic glucocorticoids or UV-therapy
  * 12 weeks for any systemic retinoids or any investigational drug
  * Patients who take any kind of contraceptive therapy (eg. estrogen, gestagen) with known positive effect on acne must be on stable dosage for a minimum of 6 month
* Underage or incapable patients
* Patients who are legally institutionalized

Primary outcomes:
measure: 50% reduction in number of lesion
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportionof subjects in Investigator global assessment (IGA)
timeFrame: Baseline to visit 3 (week 2)
measure: proportion of subjects in Investigator global assessment (IGA)
timeFrame: Baseline to visit 4 (week 4)
measure: proportion of subjects in Investigator global assessment (IGA)
timeFrame: Baseline to visit 5 (week 8)
measure: proportion of subjects in Investigator global assessment (IGA)
timeFrame: Baseline to visit 6 (week 16)
measure: proportion of subjects in Investigator global assessment (IGA)
timeFrame: Baseline to visit 7 (week 24)
measure: change in skin condition
timeFrame: at visit 3 (week 2)
measure: change in skin condition
timeFrame: at visit 4 (week 4)
measure: change in skin condition
timeFrame: at visit 5 (week 8)
measure: change in skin condition
timeFrame: at visit 6 (week 16)
measure: change in skin condition
timeFrame: at visit 7 (week 24)
measure: change in pain of the inflammatory lesions
timeFrame: at visit 3 (week 2)
measure: change in pain of the inflammatory lesions
timeFrame: at visit 4 (week 4)
measure: change in pain of the inflammatory lesions
timeFrame: at visit 5 (week 8)
measure: change in pain of the inflammatory lesions
timeFrame: at visit 6 (week 16)
measure: change in pain of the inflammatory lesions
timeFrame: at visit 7 (week 24)
measure: change in itch of the inflammatory lesions measured by a VAS
timeFrame: at visit 3 (week 2)
measure: change in itch of the inflammatory lesions measured by a VAS
timeFrame: at visit 4 (week 4)
measure: change in itch of the inflammatory lesions measured by a VAS
timeFrame: at visit 5 (week 8)
measure: change in itch of the inflammatory lesions measured by a VAS
timeFrame: at visit 6 (week 16)
measure: change in itch of the inflammatory lesions measured by a VAS
timeFrame: at visit 7 (week 24)
measure: change in quality of life
timeFrame: Baseline to visit 3 (week 2)
measure: change in quality of life
timeFrame: Baseline to visit 4 (week 4)
measure: change in quality of life
timeFrame: Baseline to visit 5 (week 8)
measure: change in quality of life
timeFrame: Baseline to visit 6 (week 16)
measure: change in quality of life
timeFrame: Baseline to visit 7 (week 24)
measure: change in depression profile
timeFrame: Baseline to Visit 3 (week 2)
measure: change in depression profile
timeFrame: Baseline to Visit 4 (week 4)
measure: change in depression profile
timeFrame: Baseline to Visit 5 (week 8)
measure: change in depression profile
timeFrame: Baseline to Visit 6 (week 16)
measure: change in depression profile
timeFrame: Baseline to Visit 7 (week 24)
measure: compliance to therapy (drug accountability)
timeFrame: at visit 3 (week 2)
measure: compliance to therapy (drug accountability)
timeFrame: at visit 4 (week 4)
measure: compliance to therapy (drug accountability)
timeFrame: at visit 5 (week 8)
measure: compliance to therapy (drug accountability)
timeFrame: at visit 6 (week 16)
measure: compliance to therapy (drug accountability)
timeFrame: at visit 7 (week 24)
measure: Frequency of adverse events (AEs)
timeFrame: at visit 3 (week 2)
measure: Frequency of adverse events (AEs)
timeFrame: at visit 4 (week 4)
measure: Frequency of adverse events (AEs)
timeFrame: at visit 5 (week 8)
measure: Frequency of adverse events (AEs)
timeFrame: at visit 6 (week 16)
measure: Frequency of adverse events (AEs)
timeFrame: at visit 7 (week 24)
measure: Frequency of adverse events (AEs)
timeFrame: at Follow-up (week 28)
measure: Seriousness of adverse events (AEs)
timeFrame: at visit 3 (week 2)
measure: Seriousness of adverse events (AEs)
timeFrame: at visit 4 (week 4)
measure: Seriousness of adverse events (AEs)
timeFrame: at visit 5 (week 8)
measure: Seriousness of adverse events (AEs)
timeFrame: at visit 6 (week 18)
measure: Seriousness of adverse events (AEs)
timeFrame: at visit 7 (week 24)
measure: Seriousness of adverse events (AEs)
timeFrame: at Follow-up (week 28)
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
state: Hessia
Study officials:
affiliation: University Hospital of Goethe-University Frankfurt
name: Andreas Pinter, MD
role: PRINCIPAL_INVESTIGATOR
References: