A Study of the Safety, Engraftment, and Action of NB01 in Adults With Moderate Acne

NCT03450369 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: NB01-P1BSA
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Acne Vulgaris

Outcome Measures

Primary Outcomes (12)

• Number of Participants With Successful Engraftment of Probiotic Following a Single Application.

  Engraftment is defined as the percentage of bacteria recovered from hair follicles that are health-associated (NB01) as measured with proprietary quantitative polymerase chain assays. Successful follicular engraftment, defined as both deoR/PanBac \>40% and Cas5/PanBac \>40% in the Day 2 (24H) ) Biore Strip samples. Cas5/PanBac and deoR/PanBac are the percentages of bacteria in a sample containing the CRISPR associated protein Cas5 and a repressor of porphyrin production deoR, respectively. Pan-Bacterial (PanBac) is a loci found in nearly all bacteria found on the face and thus serves as the denominator to calculate the percentage of bacteria with any loci.

  2 Months

• Dose Schedule Determination Based on Time to Peak deoR and Cas5

  To determine longevity of the live biotherapeutic after a single application, swab samples were collected at Baseline, 6, 24 and 48 hours after application, and genotyped as above. For each participant the absolute change, from Baseline, in the percentage of the two loci present in the live biotherapeutic (deoR and Cas5) were calculated. A significant positive change is indicative of the continued presence of the live biotherapeutic.

  From Baseline to 48 hours after application

• Number of Participants With Change in Investigator Global Assessment (IGA) Score

  Number of participants with a changed Investigator Global Assessment (IGA) score after single application of NB01; positive number if grade is reduced (e.g. from 3 to 2) or negative number is IGA grade increased. The Investigator Global Assessment 5-Point Score is a standard FDA acne assessment tool with scoring as follows: Grade 0-Clear (Clear skin with no inflammatory or non-inflammatory lesions. The category of clear should represent true absence of disease) Grade1-Almost Clear (A few scattered comedones and no more than one small papule) Grade 2-Mild (Some comedones, some papules and pustules; no nodules) Grade 3-Moderate (Many comedones, papules and pustules; one nodule may be present) Grade 4-Severe (Covered with comedones, numerous papules and pustules and no more than a few nodular lesions)

  28 Days

• Safety Profile and Tolerability of a Singly Applied NB01 Using Acne Lesion Counts.

  Absolute Lesion Count: All Lesions for the Whole Face; with higher numbers of lesion representing worsening or more severe acne

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Peeling

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Skin Peeling. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Irritant/Allergic Contact Dermatitis

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Irritant/Allergic Contact Dermatitis. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Hyperpigmentation

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Hyperpigmentation. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Ocular Irritation

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Ocular Irritation. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Conjunctival Injection

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Conjunctival Injection. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Mucosal Toxicity

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Mucosal Toxicity. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Erythema.

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Skin Erythema. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

• Number of Participants With Change in Investigator Assessment of Tolerability Score: Skin Dryness.

  Safety profile and tolerability of a singly applied NB01 using the Investigator Assessment of Tolerability Scoring (0 = None; 1 = Slight; 2 = Moderate; 3 = Intense) for Skin Dryness. Reference: ClinicalTrials.gov: Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Acne.

  From Screening to 28 days after application, typically 2 months

Study Arms (1)

NB01

EXPERIMENTAL

NB01 is a live probiotic containing a single strain of P. acnes, frozen, on a pad, in a single use pouch, for topical application. Open label and dose escalation of a single application of NB01 to subjects with moderate acne, with approximately 5 subjects assigned to lower bound dose before escalation to upper bound dose.

Biological: NB01

Interventions

NB01 BIOLOGICAL

Use an existing therapy designed to kill existing facial bacterial followed by populating facial skin with a single application of NB01

NB01

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide written informed e-consent.
• Males and Females ages 18-40.
• 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).
• 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).
• 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).
• Females with non-cyclical acne.
• 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.
• 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.

You may not qualify if:

• Active bacterial, viral, or fungal skin infections.
• 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.
• Comorbid skin conditions in the area of application.
• Active periodontal disease or ongoing procedures (e.g., gum grafting).
• History/current ocular infections/surgeries within 6 months of enrollment, with the exception of any history of cataracts.
• History of sarcoidosis.
• History septic joints/endocarditis.
• Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier.
• Sensitivity to or difficulty tolerating glycerin, polyethylene glycol.
• History of isotretinoin use, with the exception of sub-therapeutic treatment within 8 weeks of enrollment.
• Less than 80% compliance with BPO, or less than 5 days' worth of BPO pre-treatment (whichever is greater) during the Screening period.
• Current major systemic comorbid conditions.
• Currently participating in (or within 8 weeks of enrollment) another acne trial or other investigational drug.
• Participants with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices/implantable devices/hardware.
• 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.

Sponsors & Collaborators

• Naked Biome, Inc.: lead
• Dermatology Research Institute: collaborator
• QST Consultations, Ltd.: collaborator
• Science 37: collaborator

Study Sites (1)

Dermatology Research Associates

Los Angeles, California, 90045, United States

Location

Related Publications (28)

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Related Links

• \[ClinicalTrials.gov\] Investigator Assessment Tolerability Scoring: A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Facial Acne. Received: August 2009; Updated: October 2016.
• DermNet New Zealand. Acne vulgaris: Acne Grading
• \[FDA\] Guidance for Industry: Acne Vulgaris: Developing Drugs for Treatment. Draft: September 2005
• Investigator Assessment Tolerability Scoring. A Study to Evaluate Tolerability of Two Topical Drug Products in the Treatment of Facial Acne, 2009; updated 2016
• Propionibacterium acnes e a resistência bacteriana \[Propionibacterium acnes and bacterial resistance\]
• Propionibacteriales ord. Nov. In: Whitman W, et al. eds. Bergey's Manual of Systematic Bacteriology

MeSH Terms

Conditions

Acne Vulgaris

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Emma Taylor, MD CEO
• Organization: Naked Biome

emma.t@nakedbiome.com

626-260-1230

Study Officials

• Emma Taylor, MD

  CEO

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label.

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: March 1, 2018
• Study Start: January 24, 2018
• Primary Completion: June 18, 2018
• Study Completion: June 18, 2018
• Last Updated: August 3, 2020
• Results First Posted: August 3, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)