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

NCT03709654 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: NB01-P1BMA
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

Acne vulgaris is a disease caused my multiple factors including overgrowth of bacteria, clogged pores, excessive sebum production and hormonal changes. Recent literature from the Human Microbiome Project has shown there are bacterial strains specific to healthy and acne disease states (Fitz-Gibbon et al, 2013, Johnson et al, 2016, McDowell et al, 2012, Tomida et al, 2013) From this data, the investigators hypothesize that by eliminating disease-associated bacterial strains and replacing them with health-associated strains, recurrences or flares 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 multiple application study evaluating the safety, tolerability, and clinical impact that a multiple applications of NB01 have on adult subjects with moderate acne.

Conditions

Acne Vulgaris

Keywords

acne; pimple; black head; white head; zit; probiotic

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Changes in Local Skin Reactions

  Local Skin Reactions (LSRs) including Erythema, edema, erosion/ulceration, scaling/dryness, and scabbing/crusting scored at Baseline (day of first application) and Week 12 (end of treatment) and reported for each visit as: Absent, Mild, Moderate, or Severe. The number of participants (and %) with no change or improvement from Baseline to week 12 visit are reported. The number of participants (and %) whose score worsened from Baseline to week 12 visit are reported.

  Day 0 through day 80

• Number of Participants With Successful Follicular Engraftment of NB01

  Follicular engraftment sampling used Biore® Strips at Screening and day 80 (several days after end of treatment). The number of subjects with "success" at EOT where "success" is defined as a Follicular Biore® sample with "yes" outcome based on recovery of live NB01at day 80.

  12 weeks

• Absolute Change in Genotype Markers: Skin Surface Engraftment "Success"

  Skin surface engraftment "success" endpoint is defined by a change in genotype (TaqMan) markers compared to Screening; value is percentage of bacterial population containing health-associated genotype. Result is absolute change from screening value.

  Day 0 through day 80

• Absolute Change From Screening in Acne Lesion Counts

  Reporting absolute change in counts.

  Day 0 through day 80

• Percent Change From Screening in Acne Lesion Counts

  Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)

  Day 0 through day 80

• Number of Participants Achieving "Success" on Investigator Global Assessment (IGA)

  The investigator assessed the participant's inflammatory lesions on the face using the Investigator Global Assessment (IGA) 5-point scale. The scale ranges from 0 (best): clear, no evidence of papules or pustules to 4 (worst): severe, inflammatory lesions are more apparent, many papules/pustules. The outcome is the number of subjects in each treatment group achieving "success" at Week 12; "success" defined as an IGA score of "clear (score=0)" or "almost clear (score=1)" and at least a two-point reduction in IGA compared to Baseline.

  Day 0 through day 80

• Change in Acne QoL Questionnaire Score

  At each visit, subjects were asked to complete the Acne Quality of Life \[QoL\] Questionnaire to assess subjective improvement of acne with 7 response choices ranging from extremely to not at all. The total score ranges from 19 to 114; higher scores reflect improved QoL. Outcome measure is absolute change in Acne QoL (Total Score) from Baseline to Day 80.

  Day 0 through day 80

• Absolute Change From Screening in Acne Lesion Counts: Outlier Censored

  After reviewing the data, one Treatment Arm subject was found to be an extreme outlier and was censored from this ad-hoc analysis. Reporting absolute change in counts.

  Day 0 through day 80

• Percent Change From Screening in Acne Lesion Counts: Outlier Censored

  Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)

  Day 0 through day 80

• Follicular Engraftment

  Follicular communities were genotyped for health-associated loci at both Screening and 12-week visits. The percent increase of Cas5 in multiple communities from each subject is reported.

  12 weeks

Secondary Outcomes (1)

• Absolute Change in Sebum Production.

  Day 0 through day 80

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically.

Biological: NB01

Vehicle Control

PLACEBO COMPARATOR

Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically.

Other: Vehicle Control

Interventions

NB01 BIOLOGICAL

5-7 day pretreatment of gold standard benzoyl peroxide therapy to kill resident facial bacterial followed by 11 weeks of daily topical application of NB01

Treatment Arm

Vehicle Control OTHER

5-7 day pretreatment of gold standard benzoyl peroxide therapy to kill resident facial bacterial followed by 11 weeks of daily topical application of vehicle control

Vehicle Control

Eligibility Criteria

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

You may qualify if:

• Subject has provided written informed consent.
• Subject is male or non-pregnant female, 18-40 years of age, inclusive at Screening.
• Subject has moderate facial acne vulgaris
• Female subject with non-cyclical acne.
• Women of childbearing potential (WOCBP) willing to use adequate contraception during study participation
• Male subjects willing to use an acceptable method of contraception during study participation.
• Subject has the ability to personally apply benzoyl peroxide (BPO) and study drug, as per protocol.

You may not qualify if:

• Subject has active bacterial, viral, or fungal skin infections.
• Subject has active nodulocystic acne or acne conglobate, acne fulminans, or other forms of acne (e.g., acne mechanica).
• Subject is currently participating in an investigational drug, device, or biologic study or has used an investigational drug, biologic or device treatment within 30 days prior to first application of the study drug.
• Subjects with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices/implantable devices/hardware.
• Subject has a history of chronic human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infections.
• Subject has a history of malignancy (with the exception of non-melanoma skin cancer).
• Subject is immunosuppressed (such as resulting from transplantation, immunosuppressive therapy, active HIV infection/acquired immune deficiency syndrome \[AIDS\], neutropenia).
• Subject had a 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.
• Subjects with close contacts (e.g., spouses, children, or members in the same household) that have severe skin barrier defects or are immunocompromised.
• Female subject is pregnant or lactating or is planning to become pregnant and/or breast feed within the duration of study participation.
• Other entry criteria not listed above will be reviewed of each prospective subject by the study staff to confirm eligibility

Sponsors & Collaborators

• Naked Biome, Inc.: lead
• Therapeutics, Inc.: collaborator

Study Sites (3)

03

San Diego, California, 92123, United States

Location

01

Arlington, Texas, 76011, United States

Location

02

Austin, Texas, 78759, United States

Location

Related Publications (4)

• Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, Elashoff D, Erfe MC, Loncaric A, Kim J, Modlin RL, Miller JF, Sodergren E, Craft N, Weinstock GM, Li H. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013 Sep;133(9):2152-60. doi: 10.1038/jid.2013.21. Epub 2013 Jan 21.

  PMID: 23337890 RESULT

• Johnson T, Kang D, Barnard E, Li H. Strain-Level Differences in Porphyrin Production and Regulation in Propionibacterium acnes Elucidate Disease Associations. mSphere. 2016 Feb 10;1(1):e00023-15. doi: 10.1128/mSphere.00023-15. eCollection 2016 Jan-Feb.

  PMID: 27303708 RESULT

• McDowell A, Barnard E, Nagy I, Gao A, Tomida S, Li H, Eady A, Cove J, Nord CE, Patrick S. An expanded multilocus sequence typing scheme for propionibacterium acnes: investigation of 'pathogenic', 'commensal' and antibiotic resistant strains. PLoS One. 2012;7(7):e41480. doi: 10.1371/journal.pone.0041480. Epub 2012 Jul 30.

  PMID: 22859988 RESULT

• Tomida S, Nguyen L, Chiu BH, Liu J, Sodergren E, Weinstock GM, Li H. Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. mBio. 2013 Apr 30;4(3):e00003-13. doi: 10.1128/mBio.00003-13.

  PMID: 23631911 RESULT

Related Links

• DermNet New Zealand. Acne vulgaris: Acne Grading
• \[FDA\] Guidance for Industry: Acne Vulgaris: Developing Drugs for Treatment. Draft: September 2005
• Early Clinical Trials with Live Biotherapeutic FDA Guidance for Industry: Products: Chemistry, Manufacturing, and Control Information
• FDA Guidance for Industry CGMP for Phase 1 Investigational Drugs

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

  Naked Biome

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized Double Blind Vehicle Controlled Trial, dual arm with 2:1 treatment to vehicle assignment

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 17, 2018
• Study Start: November 1, 2018
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• 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 (3)