Safety, Tolerability, and Immunogenicity of ORI-A-ce001 for the Treatment of Acne Vulgaris

Study Overview
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Brief Summary
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Acne vulgaris, or acne, is one of the most prevalent diseases worldwide, with skin conditions being one of the top causes of years lived with disability and non-fatal disease burden. Despite being one of the most prevalent diseases worldwide, the most widely used treatments in acne have changed little in the past 30 years. To date there is still no effective treatment that can prevent and cure this disease. The currently available acne therapies have been discovered several decades ago, and almost no progress was made in developments of novel, breakthrough treatment approaches. The present randomized, placebo-controlled, dose escalation, Phase 1 trial (ORI-101-PAC) is intended to investigate the safety, tolerability and immunogenicity of an acne vulgaris vaccine (ORI-A-ce001) at three different dose levels in subjects aged ≥18 years suffering from moderate facial acne vulgaris who are otherwise healthy. The present study will also generate preliminary data on efficacy (inflammatory and non-inflammatory acne lesion counts, acne severity), immunogenicity and functionality of the vaccine, as well as a possible impact on skin microbiome composition. Control groups receiving placebo are included. Data from this trial will be used to inform the design of future studies.

Official Title
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A Phase I, Multi-center, Double-blind, Randomized, Dose Escalating, Parallel Group, Placebo-controlled Safety, Tolerability and Immunogenicity Study of ORI-A-ce001 for the Treatment of Facial Acne Vulgaris

Conditions
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Acne Vulgaris, Acne

Intervention / Treatment
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* Drug: ORG101 - Experimental 1
* Drug: ORG101PL - Placebo 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Male or female subject aged ≥18 years at the time of informed consent signature Female subjects of childbearing potential must have a negative serum or urine pregnancy test at Screening and before vaccination and must be willing to practice a highly effective method of contraception during the study Subject with a clinical diagnosis of moderate facial acne vulgaris (grade 3 on a 5-grade IGA scale) at Baseline Visit Subject must have a maximum of 40 non-inflammatory acne lesions (open and closed comedones) and between a minimum of 20 and a maximum of 70 inflammatory acne lesions (papules and pustules) and a maximum of 1 nodulocystic lesion (nodules and cysts) on the face (e.g., forehead, nose, cheeks, chin, upper lip) at Baseline Visit Negative Covid test at Baseline Visit Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Subject who is pregnant, lactating or is planning a pregnancy during the study period Subject who has active nodulocystic acne, acne conglobata, acne fulminans, secondary acne or other forms of acne Subject who has more than one facial nodules/cysts (where nodule/cyst is defined as an inflammatory lesion greater than or equal to 0.5 cm in size with or without cystic changes) Subject who has any skin pathology or condition that, in the Investigator's opinion, could interfere with the evaluation of the Investigational Medicinal Product (IMP) or requires use of interfering topical, systemic, or surgical therapy Subject with excessive facial hair, facial skin disorders, skin reactions that may interfere with the study assessments in the Investigator's opinion or skin infection History of Guillain-Barré-Syndrome Subject who has used any acne-affecting treatment without an appropriate washout period Subject who receives active or passive vaccination within 30 days prior to Baseline - Visit Initiation or change of hormonal contraceptive use within 12 weeks prior to Screening Visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1<br>C. acnes vaccine in adjuvanted formulation will be administered in double-blind fashion in 3 single increasing doses given i.m. | Drug: ORG101 - Experimental 1<br>* C. acnes vaccine Injection, 25 mcg, 75 mcg, 225 mcg, 4 single i.m. injections given in monthly intervals<br>|
| Placebo Comparator: Placebo 1<br>Placebo in adjuvanted formulation will be administered in double-blind fashion in single i.m. injections | Drug: ORG101PL - Placebo 1<br>* Injection, sterile aqueous solution of aluminium hydroxide, 4 single i.m. injections given in monthly intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited and unsolicited local and/or systemic adverse events (AEs) | Number of participants with AEs as assessed by electronic diary (eDiary) and/or PI assessment, and compared to placebo | 7 days following each vaccination | 
| Incidence of AEs and serious adverse events (SAEs) | Incidence of AEs and SAEs | Through study completion, an average of 9 months | 
| Number of participants with AEs or SAEs as assessed by physical examination | Number of participants with AEs or SAEs as assessed by physical examination, vital signs, local skin responses, as assessed by treatment arm (vaccine and placebo) | Through study completion, an average of 9 months | 
| Change from the baseline in laboratory data | Clinically significant change from the baseline in laboratory data as compared to placebo | Through study completion, an average of 9 months | 
| Change from the baseline in vital signs | Clinically significant change from the baseline in vital signs as compared to placebo | Through study completion, an average of 9 months | 
| Change from the baseline in ECG | Clinically significant change from the baseline in electrocardiogram (ECG) as compared to placebo | Weeks 0 and 36 | 
| Change from the baseline in physical examination | Clinically significant change from the baseline in physical examination, as compared to placebo | Through study completion, an average of 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity assessment | The amount of vaccine-antigen-specific serum antibody titers (IgG), measured by ELISA, compared to placebo and compared among different treatment groups | Weeks 0, 4, 8, 12, 16, 24 and 36 | 
| Change in inflammatory lesion counts | Absolute and percentage change from Baseline in the number of inflammatory acne lesions | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | 
| Change in non-inflammatory lesion counts | Absolute and percentage change from Baseline in the number of non-inflammatory acne lesions | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | 
| Investigator's global assessment (IGA) - change from Baseline | Absolute change in IGA score from Baseline [scores: 0-4; 0=clear, 4=severe] | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | 
| Investigator's global assessment (IGA) - percentage of subjects with improvement | Percentage of subjects with at least one-grade improvement in their Baseline IGA score (assessment of mild, clear or almost clear) [scores: 0-4; 0=clear, 4=severe] | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | 
| Assessment of subjects' treatment acceptability | Treatment acceptability, as assessed by the pre-defined questionnaire | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acne vulgaris, C. acnes, vaccine, dose escalation, first in human, FIH, skin microbiome, placebo