Acne, Acne Vulgaris
Conditions
Keywords
acne vulgaris, C. acnes, vaccine, dose escalation, first in human, FIH, skin microbiome, placebo
Brief summary
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.
Interventions
DRUGORG101 - Experimental 1
C. acnes vaccine Injection, 25 mcg, 75 mcg, 225 mcg, 4 single i.m. injections given in monthly intervals
DRUGORG101PL - Placebo 1
Injection, sterile aqueous solution of aluminium hydroxide, 4 single i.m. injections given in monthly intervals
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from the baseline in physical examination | Through study completion, an average of 9 months | Clinically significant change from the baseline in physical examination, as compared to placebo |
| Incidence of solicited and unsolicited local and/or systemic adverse events (AEs) | 7 days following each vaccination | Number of participants with AEs as assessed by electronic diary (eDiary) and/or PI assessment, and compared to placebo |
| Incidence of AEs and serious adverse events (SAEs) | Through study completion, an average of 9 months | Incidence of AEs and SAEs |
| Number of participants with AEs or SAEs as assessed by physical examination | Through study completion, an average of 9 months | 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) |
| Change from the baseline in laboratory data | Through study completion, an average of 9 months | Clinically significant change from the baseline in laboratory data as compared to placebo |
| Change from the baseline in vital signs | Through study completion, an average of 9 months | Clinically significant change from the baseline in vital signs as compared to placebo |
| Change from the baseline in ECG | Weeks 0 and 36 | Clinically significant change from the baseline in electrocardiogram (ECG) as compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in inflammatory lesion counts | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | Absolute and percentage change from Baseline in the number of inflammatory acne lesions |
| Change in non-inflammatory lesion counts | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | Absolute and percentage change from Baseline in the number of non-inflammatory acne lesions |
| Investigator's global assessment (IGA) - change from Baseline | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | Absolute change in IGA score from Baseline \[scores: 0-4; 0=clear, 4=severe\] |
| Investigator's global assessment (IGA) - percentage of subjects with improvement | Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36 | Percentage of subjects with at least one-grade improvement in their Baseline IGA score (assessment of mild, clear or almost clear) \[scores: 0-4; 0=clear, 4=severe\] |
| Assessment of subjects' treatment acceptability | Week 16 | Treatment acceptability, as assessed by the pre-defined questionnaire |
| Immunogenicity assessment | Weeks 0, 4, 8, 12, 16, 24 and 36 | The amount of vaccine-antigen-specific serum antibody titers (IgG), measured by ELISA, compared to placebo and compared among different treatment groups |
Countries
Germany
Outcome results
None listed