Clinical trial NCT03450369: A Study of the Safety, Engraftment, and Action of NB01 in Adults With Moderate Acne
Official title: A Phase 1B Dose Escalating Study of the Safety, Short-Term Engraftment and Action of a Singly-Applied NB01 in Adults With Moderate Acne
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acne Vulgaris
Lead sponsor: Naked Biome, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Dermatology Research Institute
name: QST Consultations, Ltd.
name: Science 37
First posted: 2018-03-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label.
Primary purpose: TREATMENT

Brief summary: Acne vulgaris is a multifactorial disease caused by overgrowth of Propionibacterium acnes (P. acnes), impaction of hair follicles, excessive sebum production and hormonal dysregulation. Recent literature from the Human Microbiome Project has shown there are unique microbial signatures specific to healthy and acne disease states.

From this data, the investigators hypothesize that by eliminating resident disease-associated bacterial strains and replacing them with health-associated strains, recurrences/fares of acne may be improved, mitigated, and prevented. Instead of current approaches which focus on eliminating all bacteria from the skin, the investigators aim to deliver healthy bacteria to restore the skin to a healthy state via this replacement therapy.

The investigators aim to test this in a Phase Ib single application study evaluating the safety, tolerability, and clinical impact that a single application of NB01, a live strain of P. acnes, has on adult subjects with moderate acne.

Detailed description: A Phase 1B Dose Escalating Study of the Safety, Short-Term Engraftment and Action of a Singly Applied NB01 in Adults with Moderate Acne

Acne vulgaris is a multifactorial disease caused by overgrowth of Propionibacterium acnes (P. acnes), impaction of hair follicles, excessive sebum production and hormonal dysregulation. Recent literature from the Human Microbiome Project has shown there are unique microbial signatures specific to healthy and acne disease states.

From this data, the investigators hypothesize that by eliminating resident disease-associated bacterial strains and replacing them with health-associated strains, recurrences/fares of acne may be improved, mitigated, and prevented. Instead of current approaches which focus on eliminating all bacteria from the skin, the investigators aim to deliver healthy bacteria to restore the skin to a healthy state via this replacement therapy.

The investigators aim to test this in a Phase Ib single application study evaluating the safety, tolerability, and clinical impact that a single application of NB01 has on adult subjects with moderate acne. Investigators will be profiling the change in microbiome over the course of therapy to determine if exogenously delivered bacteria can populate the skin (engraftment) and cause a shift in the microbiome safely and subsequently impact acne biomarkers that may correlate with clinical disease.

The investigators intend for this therapy to eventually be used in acne subjects with ages ranging from 13-40, and all disease severities as either monotherapy for mild to mild/moderate acne and as an adjuvant therapy for moderate to severe acne at all body sites, with special attention to facial involvement.

This approach is standard to acne therapy whereby mild disease will be treated with a monotherapy (i.e., topical Benzoyl peroxide \[BPO\]) and moderate/severe disease will be treated with various combinatory regimens (topical antibiotics, BPO, topical retinoids, oral antibiotics).

Primary Objectives:

1. To determine the safety profile and tolerability of a singly applied NB01
2. To define engraftment of a singly applied topical NB01.
3. Dose schedule determination based on engraftment

Secondary Objective: To evaluate clinical efficacy using FDA standards of acne clinical assessments, namely the Investigator Global Assessment (IGA) and acne lesion counts of a singly applied NB01.

Approximately 10 total male and female adult subjects combined with moderate, non-cyclical acne will be enrolled into the trial. Approximately five (5) subjects will be assigned to each dose schedule

This is a single topical application study of live bacteria for the study of acne in adult subjects.

Subject participation in the trial will range from 5 weeks to 2 months.

Eligibility criteria: Inclusion Criteria:

1. Ability to provide written informed e-consent.
2. Males and Females ages 18-40.
3. Acne severity: Moderate (Grade 3 on 5-point IGA scale and Moderate on an acne lesion count scale (Appendix B \[Section 12.2\], IGA and Lesion Count Acne Grading).
4. Acne treatment-free period (including topical or oral antibiotics, retinoids, laser therapy, topical dapsone, topical azelaic acid, facial peels, dermabrasion, sulfacetamide sulfur, and salicylic acid), of at least 3 weeks prior to e-consent (with the exception of BPO pre-treatment under this protocol).
5. Lesion count: A minimum of at least a total of 15 inflammatory lesions (papules plus pustules), with a minimum of 10 inflammatory lesions within the designated application area (cheek/nose).
6. Females with non-cyclical acne.
7. Females of childbearing potential willing to use adequate contraception (e.g., total abstinence, intrauterine device (IUD), barrier method with spermicide, surgical sterilization or surgically sterilized partner, Depo-Provera®, Norplant®, or NuvaRing® for the duration of the Screening Period and during study participation. All oral contraceptive and hormonal implants will need to have been initiated and on a stable dose for at least 3 months prior to the screening period. Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal; postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.
8. Male participants willing to use an acceptable method of contraception (e.g., total abstinence, barrier methods with spermicide, surgical sterilization or surgically sterilized partner) during study participation.

Exclusion Criteria:

1. Active bacterial, viral, or fungal skin infections.
2. Any noticeable breaks or cracks in the skin on the face, including severely excoriated skin or skin with open or weeping wounds suggestive of an active infection or increased susceptibility to infection.
3. Comorbid skin conditions in the area of application.
4. Active periodontal disease or ongoing procedures (e.g., gum grafting).
5. History/current ocular infections/surgeries within 6 months of enrollment, with the exception of any history of cataracts.
6. History of sarcoidosis.
7. History septic joints/endocarditis.
8. Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier.
9. Sensitivity to or difficulty tolerating glycerin, polyethylene glycol.
10. History of isotretinoin use, with the exception of sub-therapeutic treatment within 8 weeks of enrollment.
11. Less than 80% compliance with BPO, or less than 5 days' worth of BPO pre-treatment (whichever is greater) during the Screening period.
12. Current major systemic comorbid conditions.
13. Currently participating in (or within 8 weeks of enrollment) another acne trial or other investigational drug.
14. Participants with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices/implantable devices/hardware.
15. Participants with close contact (e.g., spouses, children, or members in the same household) with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices/implantable devices/hardware.
16. Known chronic human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infections.
17. History of malignancy (with the exception of non-melanoma skin cancer).
18. Immunosuppression (such as resulting from transplantation, immunosuppressive therapy, active HIV infection/acquired immune deficiency syndrome \[AIDS\], neutropenia).
19. Major surgical procedure, open biopsy, or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed), or anticipation of the need for major surgery during the study.
20. The presence of a medical or psychiatric condition, history of drug or alcohol abuse that, in the opinion of the PI, makes the subject inappropriate for study inclusion.
21. Participants with close contacts (e.g., spouses, children, or members in the same household) that have severe barrier defects or are immunocompromised.
22. Inability or unwillingness of participant to comply with study protocol procedures.
23. Pregnant or lactating females, or females who desire to become pregnant and/or breast feed within the duration of study participation.
24. Imprisonment or under legal guardianship.

Primary outcomes:
measure: Number of Participants With Successful Engraftment of Probiotic Following a Single Application.
timeFrame: 2 Months
measure: Dose Schedule Determination Based on Time to Peak deoR and Cas5
timeFrame: From Baseline to 48 hours after application
measure: Number of Participants With Change in Investigator Global Assessment (IGA) Score
timeFrame: 28 Days
measure: Safety Profile and Tolerability of a Singly Applied NB01 Using Acne Lesion Counts.
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Peeling
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Irritant/Allergic Contact Dermatitis
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Hyperpigmentation
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Ocular Irritation
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Conjunctival Injection
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Mucosal Toxicity
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Erythema.
timeFrame: From Screening to 28 days after application, typically 2 months
measure: Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Dryness.
timeFrame: From Screening to 28 days after application, typically 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
Study officials:
affiliation: CEO
name: Emma Taylor, MD
role: STUDY_DIRECTOR
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