Non-interventional Translational Study in Mild, Moderate and Severe Acne Patients (VBE00011)

This study aims to uncover the specific immunopathology, microbiome and pathophysiology of acne vulgaris in people living in a tropical climate such as Singapore. This is a largely unexplored population in terms of acne pathogenesis, and will lead to population-specific interventions for the management of acne vulgaris.

Study Overview

• Status: Not yet recruiting
• Conditions: Acne

Detailed Description

The main objective of this translational study in healthy participants and in mild, moderate and severe acne participants is to deepen the current understanding of acne aetiology. A multi-omics approach will be leveraged to analyse the interactions between the local skin microbiota and host factors found in different stages of acne vulgaris and generate hypotheses on how these may contribute to different disease manifestations.

General objectives:

I. Deepen the current understanding of acne aetiology II. Identify key biological markers of disease severity and specific immune pathways III. Describe bacterial components associated with disease severity and inflammatory immune response IV. Determine antigens of the natural immune response against C. acnes

Data collected from participants includes:

• Demographic Data [age, sex, ethnicity, body mass index (BMI)]
• Skin type (using the Fitzpatrick skin classification scale)

Samples collected from participants:

• Pore Strip Application (comedo extraction)
• Facial swabbing
• Facial tape stripping
• Blood Samples
• Facial biopsies (optional)

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Etienne Wang Cho Ee Senior Consultant, MBBS; Phone Number: +65 6253 4455; Email: etienne@nhghealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants aged 18 to 25 years, with or without mild, moderate, or severe acne will be recruited from the Singapore population.

Description

INCLUSION CRITERIA:

AGE I01: Aged 18 to 25 years on the day of inclusion.

TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS

I02: Participants with a formal diagnosis of either:

• Mild facial acne vulgaris defined as Investigator's Global Assessment (IGA) of 2, or
• Moderate facial acne vulgaris defined as IGA score of 3, or
• Severe facial acne vulgaris defined as IGA score of 4, or
• Healthy volunteers without acne defined as IGA score of 0.

INFORMED CONSENT I03: Informed consent form has been signed and dated by participant capable of providing informed consent.

Note: For minor participants, informed consent form must also be signed and dated by the parent(s) or another legally acceptable representative(s).

OTHER INCLUSIONS I04: Participant or participant and parent(s)/legally acceptable representative(s) are able to attend all scheduled visits and to comply with all study procedures.

EXCLUSION CRITERIA

Participants are not eligible for the study if any of the following criteria are met:

MEDICAL CONDITIONS E01: Thrombocytopenia, presence of bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating blood sampling, currently or previously suffering from any immune disorder.

E02: Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion.

E03: Active nodulocystic acne, acne conglobata, acne fulminans, secondary acne (eg, chloracne, drug-induced acne) or other forms of acne (eg, acne mechanica).

E04: Skin pathology or condition that, in the investigator's opinion, could interfere with the evaluation of the study intervention or requires use of interfering topical, systemic, or surgical therapy.

E05: Excessive facial hair, facial tattoos, facial skin disorders, skin reactions that may interfere with the study assessments in the investigator's opinion (including - but not limited to - actinic keratosis, eczema, psoriasis, seborrheic dermatitis, rosacea, acute or recent sunburn) or skin infection.

E06: Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion.

E07: Self-reported or documented seropositivity for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.

E08: Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of samplings. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

PRIOR/CONCOMITANT THERAPY:

E09: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within 6 months prior to the study sample collection; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) within 3 months from study sample collection.

E10: Start or switch of hormonal contraceptive use within 12 weeks prior to the study visit.

E11: Previous use of oral isotretinoin. E12: Use of any acne-affecting treatment without an appropriate washout period (antibacterial/antifungal/antiseptic medications or topicals). Participants receiving prohibited medications/therapies at Screening Visit will have to observe a washout period of 2 to 24 weeks before enrolment to preserve eligibility in the study.

E13: Previous vaccination against C. acnes with an investigational vaccine E14: Receipt of immune globulins, blood or blood-derived products in the past 3 months E15: Pregnant or lactating women

PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE E16: Participation at the time of study enrolment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.

OTHER EXCLUSIONS:

E17: Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

E18 Identified as an Investigator or employee of the Investigator or study centre with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy Participants
Mild Acne
Moderate Acne
Severe Acne

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acne lesion counts	The number of total lesions, inflammatory lesions (papules and pustules), and non-inflammatory lesions (open and closed comedones) on the face will be counted. All lesions on the face should be counted, including those on the nose. Counts of nodulocystic lesion (nodules and cysts) will be reported separately and are not to be included in the inflammatory or non-inflammatory lesion counts.	2 years
Investigator's Global Assessment (IGA) Scale	The overall severity of facial acne will be assessed using the 5-point IGA scale (Table 6) (15). Each grade is defined by a distinct and clinically relevant morphologic description that minimizes interobserver variability. The IGA severity score assessments should be performed exclusively by site staff qualified as IGA rater. Investigators or designee should use the IGA scale provided in the study protocol throughout the study.	2 years
Patient Reported Outcome Measures	With the objective of evaluating the impact of different acne severities in the quality of life, participants will be asked to complete 2 quality of life (QoL) questionnaires: the Skindex-29 and the Acne-specific Quality of Life (Acne-QoL). The Skindex-29 questionnaire is a validated health-related quality of life self-administered questionnaire to assess the impact of skin diseases on patient's quality of life (17). Skindex-29 consists of 30 items, distributed into 3 domains (symptoms, emotion and function. Each item is scored on a 5-point Likert scale, from 1 to 5. Scores are standardized to 100, with lower score indicating higher levels of QoL. The Acne-QoL is a validated health-related quality of life self-administered questionnaire to assess quality of life among participants with facial acne (16). Acne-QoL consists of 19 items organized into 4 domains: self-perception, role-social, role-emotional and acne symptoms. Each item is scored	2 years
Facial Photographs	The investigator or designee will take digital photographs of the participants' face using Canfield Facial Image Photography Device. Photographs will be taken under standardized conditions. Images will be captured, viewed, and uploaded using Canfield Facial Image Photography Device software which automatically checksums, encrypts, packages, and transfers the data to secure, validated and compliant web servers hosted by Canfield Clinic. Deidentified images will be used to assess the skin condition of each participant and be the input data for the AI-based tool to derive acne severity.	2 years
Application of AI-based methods for assessing acne severity from images	Images will be analyzed with experimental AI technologies to develop and improve acne lesion count and severity grading. Deep learning-based methods will be used to automatically detect various categories of acne lesions and assess acne severity by quantifying the number of lesions in each category. The deep learning model will be trained on the dataset with ground truth bounding box labels annotated by dermatologists, enabling it to identify lesion locations and classify each lesion type, such as inflammatory lesions (papules, pustules, nodule, and cysts), noninflammatory lesions (open comedo and closed comedo), and others (eg, scar, melasma, and nevus). Facial images for the study are captured using the Canfield Facial Image Photography Device, ensuring high-quality, standardized input for robust model performance. The trained model will output bounding boxes with lesion classifications for test images, providing a detailed and objective assessment of acne severity based on lesion c	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Assessments	1.Surface Binding (SB) assays using a fluorescence cytometer will be used to determine the binding efficiency of serum antibodies to the cell surface of live C. acnes bacteria. 2. Opsonophagocytic killing (OPK) assays will be used to determine the ability of antibodies to induce opsonization of C. acnes bacteria. Bound antibodies mobilize and activate immune cells against the bacterium, leading to a reduction in the bacterial cell numbers. 3. Sheep Red Blood Cells Co-Hemolysis Neutralization Assay will be used to measure serological titers of neutralizing recombinant C. acnes CAMP2 polypeptide (CAMP2)-specific antibodies. 4. Antigen-specific Antibody Titers to further explore the humoral immune response elicited against C. acnes (e.g. C. acnes types IA1 [NCTC737], IB [KPA171202]), IgG, IgA titres and IgG subclasses distribution will be measured.	2 years
Immunogenicity Assessments	5. Antibody-dependent complement deposition titer documents the ability of C. acnes-specific Ig to activate the complement system via the classical pathway. For tested serum samples, the method consists of measuring the antibody-driven recruitment and deposition of the complement components C3b/iC3b on live C. acnes bacterial using flow cytometry. 6. Cell-Mediated Immunity against C. acnes antigens cytokine assessment in supernatant from whole blood culture, the cytokine responses in whole blood will be measured by either multiplex bead array assay or MSD ECL-based assay.7.Immunophenotyping of Peripheral Blood Mononuclear Cells (PBMCs) T cell profiling by flow cytometry subsequent to stimulation. PBMCs isolated from participants will be thawed and cultured with relevant reagents and then evaluated using cytometry, using BD analyzers, spectral flow and/or CyTOF as required as required to determine activated T cell signatures.	2 years
Immunogenicity Assessments	8. Peripheral blood cytokine concentration will be measured in the serum of participants by either multiplex bead array assay or MSD ECL-based assay or appropriate proteomics profiling platforms such as NULISA or OLINK. 9. Genomewide genetic analysis, DNA will be extracted from PBMCs isolated from the blood collected from each participant. This DNA will then be used for genetic analysis using genomewide genotyping arrays such as Infinium (Illumina).	2 years
METAGENOMIC AND METATRANSCRIPTOMIC ASSESSMENTS	To characterize the microbial strains, microbiome composition and transcriptional activity, skin swabs will be collected from the participants' forehead and cheeks. For sequencing assays, material from swabs will be dislodged and submerged in DNA/RNA shield and stored at -80°C prior to nucleic acid extraction. Microbial isolation will be done according to procedures described in 4.6. Analyses such as microbiome metagenomics profiling (taxonomic profiles, relative abundance, diversity, richness) and amplicon sequencing of isolates (C. acnes Single Locus Sequence Type) could be performed alongside similar analysis from follicular extracts. Alongside this metatranscriptomic analysis of collected microbial material will be undertaken. Collected samples will be processed and stored at sites according to the best practice for each material type prior to downstream analytical assays.	2 years
SPATIAL AND SINGLE CELL RNA SEQUENCING	Skin biopsies will be obtained and stored in an appropriate media (e.g. RPMI, PBS, or formalin) by clinical staff and kept at 4°C to await transport to A*STAR. To study components of the acne microenvironment skin biopsies will be prepared and analysed following best practices and aligned with manufacture's protocols for spatial and/or single cell RNAseq. Data will be pre-processed using the supplier's pipeline. For downstream analysis, including normalization, integration, dimensionality reduction, annotation and detection of differentially expressed genes, the resulting matrices will be processed using R or Python packages such Seurat or Monocle or by vendor specific programs.	2 years
SKIN SURFACE MATERIAL ASSESSMENTS OR METABOLIC AND PROTEOMIC ASSESSMENTS	Skin surface material assessment such as metabolomics or proteomics will be performed from skin tape strips to detect small molecules and larger lipids including ceramides, fatty acids, and triglycerides or skin surface protein expression. Skin tapes material will be extracted with organic solvents and injected into dual-column liquid chromatography-triple quadrupole mass spectrometry for high-throughput metabolomics measurements. Similarly, skin tape material could be extracted for proteomics analysis prior to LC-MS/MS analysis. Multivariate analyses will be conducted to differentiate participant group clustering and identification of top metabolites or proteins driving these differences.	2 years
MICROBIAL ISOLATION	Isolation of microbes from the skin surface and/or the follicular ostia will be performed with automation and/or standard selective culture and plating techniques. We will use conditions to mainly target C. acnes strains as the species of particular interest. Other strains such as Staphylococcus spp. may also grow under similar conditions that will also be isolated and banked for study. Representative isolates will be genome sequenced (Illumina) and genome assembled for phylotyping and gene analysis such as for virulence/vaccine target.	2 years

Collaborators and Investigators

• Sponsor: National Skin Centre
• Collaborators: Sanofi; A*Star

Publications and helpful links

General Publications

• Liu PF, Hsieh YD, Lin YC, Two A, Shu CW, Huang CM. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris. Curr Drug Metab. 2015;16(4):245-54. doi: 10.2174/1389200216666150812124801.
• Keshari S, Kumar M, Balasubramaniam A, Chang TW, Tong Y, Huang CM. Prospects of acne vaccines targeting secreted virulence factors of Cutibacterium acnes. Expert Rev Vaccines. 2019 May;18(5):433-437. doi: 10.1080/14760584.2019.1593830. Epub 2019 Mar 28.
• Goh E, Chavatte JM, Lin RTP, Ng LFP, Renia L, Oon HH. Vaccines in Dermatology-Present and Future: A Review. Vaccines (Basel). 2025 Jan 26;13(2):125. doi: 10.3390/vaccines13020125.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): February 14, 2028
• Study Completion (Estimated): February 14, 2029

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 6, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Skin and Connective Tissue Diseases; Acne Vulgaris
• Other Study ID Numbers: 2025-1033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Collaborators still undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No