Pirfenidone Plus M-DDO Gel in Moderate and Severe Acne
Condition: Acne Vulgaris Superficial Mixed Comedonal and Inflammatory
MeSH terms: Acne Vulgaris
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Acne vulgaris is a complex skin disorder involving multiple abnormalities of the
      pilosebaceous unit. Acne is the most common skin disease during puberty and worsens
      throughout adolescence. However, epidemiological studies suggest that acne can arise at any
      age, most frequently affecting individuals between puberty and 30 years of age, with 79%-95%
      of subjects aged between 16 years and 18 years and 80% of subjects between puberty and 30
      years of age. Acne is considered the main reason for consultation with the dermatologist in
      institutional and private clinical practice.

      Clinical features include seborrhoea, non-inflammatory lesions, inflammatory lesions and
      various degrees of scarring. There are many classifications of acne and scarring severity.
      Moderate to severe acne is about 15-20%.

      Facial acne scarring affects both sexes equally and occurs to some degree in up to 95% of
      cases. There is a significant correlation between the initial acne grade and the overall
      severity of scarring at all sites and in both sexes. This would suggest that treatment aimed
      at reducing the severity of acne might reduce the incidence of scarring. Both superficial
      inflammatory acne lesions as well as deep nodular lesions seem capable of producing scars.

      Conventional therapies recommended for the treatment of acne vulgaris include retinoids,
      benzoyl peroxide (BPO), antibiotics, and hormonal therapy. Combination therapy using agents
      with complementary mechanisms provides the opportunity to target multiple pathogenetic causes
      of acne vulgaris.

      The combination in gel with 0.1% adapalene and 2.5% BPO is a once-daily treatment of acne
      vulgaris. In several double- blind, randomized controlled trials (RCTs), the Adapalene-BPO
      (A-BPO) combination therapy applied once daily for 12 weeks significantly reduced the number
      of both inflammatory and non-inflammatory lesions in subjects with moderate acne vulgaris. In
      Mexico there is an available commercial product of this combination (Effezel®; Galderma). The
      limitation of this topical therapy is the low tolerability by patients as they can experiment
      several levels of irritation, erythema, dryness, desquamation, burning, and itching), and
      patients are advised to expect these side effects, which contribute to discontinue therapy if
      it becomes severe.

      On the other hand, 5-methyl-1-phenyl-2-(1h)-pyridone or pirfenidone (PFD) is a wide-spectrum
      antifibrotic drug that modulates diverse cytokines action, involving TGF-β, TNF-α, epidermal
      growth factor, platelet-derived growth factor, VEGF, IGF-1, fibroblast growth factor,
      interferon-γ, interleukin (IL)-1, IL-6, and IL-8 and it has shown promising effects in vitro
      and in vivo settings. Also, PFD has proven effective in the prevention and regression of
      pulmonary fibrosis, peritoneal sclerosis, hepatic cirrhosis, uterine fibromyoma, left
      ventricular fibrosis, renal interstitial fibrosis, and breast capsular contracture in
      experimental models. A recently open phase II clinical trial evaluated the therapeutic use of
      PFD gel in localized scleroderma. Results showed it acts on both the inflammatory and the
      fibrotic phases.

      The other component of Zaxcell is modified-diallyl disulfide oxide (M-DDO) an antimicrobial
      and antiseptic agent, which has been proved in patients with chronic diabetic ulcer as a
      potent germicide and has show to increase the beneficial effect of PFD preventing infections,
      accelerating and improving ulcer resolution. (Observations not published).

      According to this, the investigators believe that Zaxcell (PFD + M-DDO) could play an
      important role in the modulation of inflammatory and scarring process in acne. The
      investigators hypothesis is that PFD in patients with moderate to severe acne modulates
      amplification of the inflammatory response, regulating the inflammasome activation,
      macrophage polarization and its activity in regulating the wound healing process of the skin
      in an early fashion.

      Zaxcell is an innovative gel with a synergetic mode of action that could modulate the
      inflammatory response. Furthermore, has antiseptic properties and regulates the process of
      wound healing, fibrogenic and scarring process. In vitro and in vivo studies provide an
      initial body of evidence on the safety and clinical benefits of PFD, the main component of
      Zaxcell as a promising candidate for the treatment of moderate to severe acne.
    

Detailed description: 
      Participants will be randomized using a random number table to distribute in the control
      (Effezel) and the experimental group (Pirfenidone+M-DDO). Before screening, participants will
      undergo an informed consent process and they will sign an institutional review board-approved
      informed consent form. The study will be conducted in accordance with Good Clinical Practices
      and the principles that have their origins in the Declaration of Helsinki (revised Seoul,
      Korea, 2008). Potential subjects with acne scars will be selected from the investigators
      practices and solicited from advertisements. To be included, subjects must have met the
      inclusion criteria. Demographics data and medical history will be registered on a monthly
      basis. Before treatment, all subjects with inflammation and scars will be evaluated in the
      face and back area using the Investigator´s Global Assessment scale (IGA scale) and all the
      lesions will be counted. The face and back area affected will be mapped and photographed.
      Participants in the experimental group will receive topical Zaxcell (Pirfenidone 10% +M-DDO
      gel) two times a day on the face and superior back and patients in control group will receive
      Effezel (Adapalene 0.1%+Benzoyl peroxide 2.5%) once a day. Both groups will apply the topical
      treatment in acne on the face and superior back area for six months previous cleansing of the
      area with neutral soap. Two biopsies of skin will be taken at the beginning, at month one and
      month 3 from the back area where the treatment will be applied. After this time, only
      clinical evaluations and photographs will be performed. Participants will be evaluated at
      every month until 6 months after their last application.
    

Intervention name(s): PDF+M-DDO; A+PBO
Intervention type(s): Combination Product; Combination Product
Intervention description(s): Participants with moderate and severe acne will be treated two times a day on the face and superior back with a smooth layer (standard finger tip unit 0.5 g for an area of 100 to 120 square centimeters) of Zaxcell (Pirfenidone with M-DDO) in form of a gel. Patients have to wait 20 min without cover those sites.; Participants with moderate and severe acne will be treated once a day (at night) on the face and superior back with a smooth layer (standard finger tip unit 0.5 g for an area of 100 to 120 square centimeters) of Effezel (Adapalene with benzoyl peroxide) in form of a gel. Patients have to wait 20 min without cover those sites
Other intervention name(s): Zaxcell; 5-methyl-phenyl-2(1h)- pyridone with M-DDO; Effezel; Adapalene with benzoyl peroxide
Intervention MeSH terms: Adapalene; Benzoyl Peroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Modified diallyl disulfide oxide (M-DDO); Pirfenidone (PFD); Adapalene + Benzoyl peroxide (A-BPO)