Anti-inflammatory Effects of Topical Erythromycin and Clindamycin in Acne Patients

NCT03883269 | Recruiting Phase 4 FDA Drug

• 1 other identifier: CHDR1732
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The combined bacteriostatic and immunomodulatory effects of erythromycin and clindamycin will be explored. Treatment effects will be extensively characterized by conventional methods including lesion counts, global assessment scales and visual grading as well as state-of-the-art methodology, including multi-modal photo analysis, perfusion by laser speckle contrast imaging, analysis of local skin surface, biopsy biomarkers and skin microbiota. This extensive response profiling, combined with the mechanistic insights from concurrent in vitro and in vivo studies in healthy volunteer challenges, will increase the understanding of erythromycin's and clindamycin's effects in acne vulgaris.

Conditions

Acne Vulgaris

Outcome Measures

Primary Outcomes (12)

• Efficacy endpoint 1 - Change in lesion count

  The inflammatory lesions include papules pustules and nodules/cysts. At screening and every study visit, the evaluator will count the inflammatory lesions separately by area on the face (forehead, right cheek, left cheek, chin and nose). All lesion counts during the treatment and follow-up period will be performed by a treatment-blinded evaluator

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Efficacy endpoint 2 - Change in investigator Global Assessment acne (IGA)

  Acne severity will be assessed at screening and every study visit by the Investigator Global Assessment for facial acne (clear, almost clear, mild, moderate, severe, very severe). This will be done by a treatment blinded evaluator.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Change in Patient Reported Outcome (PRO)

  Pre-dose and at EOT patients will be asked how they would rate their acne that day using the subjective Patient Global Assessment (clear, almost clear, mild, moderate, severe, very severe)

  Day 0 and day 28

• Pharmacodynamic endpoints 1 - Change in Standardized facial photography by Canfield Visia and via selfie app

  A standardized set of 3 facial photos (front, left, right) will be taken every study visit by Canfield Visia CR. Furthermore, patients will take daily selfies with a validated mobile app.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 2 - Change in Sebum measurements by Sebumeter®

  Sebum excretion will be measured every study visit by Sebumeter®. The measurement will be repeated for 3 times and the average will be used for the analysis.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 3 - Change in Perfusion by Laser Speckle Contrast Imaging (LSCI)

  Cutaneous microcirculation will be assessed using the laser speckle imager (LSCI; PeriCam PSI System, Perimed Jäfälla, Sweden). Measurements have to be performed in a temperature controlled room with a temperature around 22°C. The subject has to get accommodated to the room temperature for a minimum of 15 minutes prior to testing. After this, the speckle assessments can commence. Briefly, the subject will be resting for at least ten minutes before any measurements take place. A suitable area of the face will be identified. This area will be illuminated' by the laser and the response signal will be captured. If no suitable area can be identified, the measurement will not be performed and data will be entered as missing.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 4 - Change in Morphology by Optical Coherence Tomography (OCT)

  Skin morphology will be assessed by optical coherence tomography at every study visit. Optical coherence tomography uses reflected light returning from skin tissue to create an image of the skin and 2 mm below the skin. The visualization can be done because different skin structures reflect light in a different way and can therefore be distinguished. Optical coherence tomography is similar to ultrasound however instead of sound it uses light refraction to visualize tissue.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 5 - Change in Local skin biopsy biomarkers

  Two-millimetre punch biopsies are taken at day 0 and day 28 from a papule or pustule. Moreover, at day 0 a biopsy will be taken from nonlesional non-facial skin (upper back) as healthy control. The biopsies will be placed in RNAlater medium directly after harvest of the biopsy and stored at 4°C. Biomarker sequencing will be performed by RNA extraction and quantitative PCR will be performed for a subset of immunomodulatory biomarkers (including but not limited to IL-1b, IL-1a, TNF-a IL-6, IL-12, IL-8, IL-10, IL-17, IFN-g).

  Day 0 and day 28

• Pharmacodynamic endpoints 6 - Change in Local skin surface biomarkers by TAP

  Skin biomarkers will be measured pre-dose and after 7, 14, 21, 28, and 42 days by TAP (FibroTx, Estonia). TAP consists of a multiplex capture-antibody micro-array that is supported by a dermal adhesive bandage for fixture to skin. When TAP is applied to skin and left on for 20 minutes, the antibodies printed on the micro-array capture biomarkers from skin through immune recognition. Biomarkers (IL-1a, IL-1b, TNF-a, IL-8, IL-6, IL-17) captured from skin by TAP are qualitatively and quantitatively analyzed by spot-ELISA by a specific TAP analyzer.

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 7 - Change in skin microbiota

  The skin swab will be placed in a 2 ml lysis tube containing DNA/RNA shield to stabilize and preserve the DNA. The DNA extraction will be performed using adapted DNA extraction method based on the Zymo Research fecal DNA extraction methodology. The microbiome will be analyzed according to 16S rRNA gene sampling

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 8 - Change over time in p. acnes cultures

  Swabs of predefined lesional (papule of pustule) and non-lesional skin will be taken with a sterile cotton swab. Colony numbers (colony forming units - CFU) and minimal inhibitory concentrations (MIC) will be reported. In addition, swabs of other lesions (i.e. nodules or scars) may be taken if applicable. Moreover, in order to study P. acnes in the pilosebaceous unit a comedo extraction will be performed and the sebum will be cultured for P. acnes. Comedo extraction will be performed if applicable (i.e. if the patient has comedones).

  Day 0, day 7, day 14, day 21, day 28 and day 42

• Pharmacodynamic endpoints 9 - Change over time in faecal microbiota

  Faecal samples will be collected at home. Subjects will use a 'faeces catcher' in their toilet and afterwards use a cotton swab to transfer a scoop of faeces to a 2 ml lysis tube (REF ZY-R1103, Zymo Research) containing DNA/RNA shield to stabilize and preserve the DNA.

  before day 0 and after day 28

Study Arms (3)

Erythromycin 4%

EXPERIMENTAL

Erythromycin 4% topical gel formulation, BID, 4 weeks

Drug: Erythromycin 4% topical gel formulation

Clindamycin 1%

EXPERIMENTAL

Clindamycin 1% topical lotion formulation, BID, 4 weeks

Drug: Clindamycin 1% topical lotion formulation

ethanol solution

PLACEBO COMPARATOR

70% topical ethanol solution, BID, 4 weeks

Drug: 70% topical ethanol solution

Interventions

Erythromycin 4% topical gel formulation DRUG

Erythromycin 4% topical gel formulation, BID, 4 weeks

Erythromycin 4%

Clindamycin 1% topical lotion formulation DRUG

Clindamycin 1% topical lotion formulation, BID, 4 weeks

Clindamycin 1%

70% topical ethanol solution DRUG

70% topical ethanol solution, BID, 4 weeks

ethanol solution

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects, 18 to 45 years of age. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease other than AV following a detailed medical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, virology and urinalysis;
• Mild to moderate inflammatory acne vulgaris on the face, ≥5 inflammatory lesions (papules and/or pustules), present at screening and baseline visit
• A maximum of 5 nodules present at screening and baseline visit
• Inflammatory acne present for at least 6 months
• Fitzpatrick skin type I-II (Caucasian)
• Able and willing to give written informed consent and to comply with the study restrictions.
• Willing to comply with 2x2mm facial skin punch biopsies

You may not qualify if:

• Severe acne where systemic treatment is needed
• Use of any topical (anti-acne) medication (prescription or OTC) within 2 weeks prior to baseline
• Use of any oral/systemic treatment for acne, including oral antibiotics, excluding OAC, within 4 weeks prior to baseline
• Use of systemic isotretinoin within 6 months prior to baseline
• History of pathological scar formation (keloid, hypertrophic scar)
• Known hypersensitivity to erythromycin or clindamycin, drugs of the same class, or any of their excipients.
• Known contact dermatitis reaction to any product
• Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment.
• Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
• Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening
• Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding

Sponsors & Collaborators

• Centre for Human Drug Research, Netherlands: lead
• Maruho Co., Ltd.: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

RECRUITING

MeSH Terms

Conditions

Acne Vulgaris

Interventions

Erythromycin; Clindamycin

Condition Hierarchy (Ancestors)

Acneiform Eruptions; Skin Diseases; Skin and Connective Tissue Diseases; Sebaceous Gland Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Robert Rissmann, PharmD, PhD

  CHDR

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Rissmann, PharmD, PhD

CONTACT

+31 71 5246 400; clintrials@chdr.nl

Diana Noort

CONTACT

+31 71 5246 400; clintrials@chdr.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Evaluator-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized, open-label, placebo-controlled, evaluator-blinded study.

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: March 20, 2019
• Study Start: March 20, 2018
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 20, 2019

Record last verified: 2019-03

Locations

NL (1)