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

• Sponsor: Naked Biome, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03709654
• Collaborator: Therapeutics, Inc. (Industry)
• Enrollment: 36
• Locations: 3
• Arms: 2
• Actual Duration (Months): 10.9
• Patients Per Site: 12
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Biological: NB01; Other: Vehicle Control	Phase 1

Detailed Description

A Multicenter, Randomized, Double-Blind, Vehicle-Controlled Phase 1B Study of the Safety, Short-Term Engraftment and Action of 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 (NB01) to restore the skin to a healthy state via this replacement therapy.

The investigators aim to test this in a Phase 1B multiple application study evaluating the safety, tolerability, and clinical impact that a multiple, daily, applications 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 and tolerability of a multiple application of topical P. acnes microbiome transplant ("NB01").

Exploratory Objectives:

1. To define engraftment duration of NB01.

2. To evaluate preliminary clinical efficacy using Acne Lesion Counts (total, inflammatory, and non-inflammatory), Investigator Global Assessment (IGA), and subjective improvement of acne based on subject reported outcomes (Acne QoL Questionnaire).

3. To evaluate treatment effects, based on sebum production in a subpopulation from sites 02 and 03.

Approximately 36 total male and female adult subjects combined with moderate, non-cyclical acne will be enrolled into the trial. Approximately twenty four (24) subjects will be randomly assigned treatment and twelve (12) subjects will be randomly assigned to vehicle control.

This is a multiple topical application study of live bacteria for the study of acne in adult subjects. Following a 5-7 day pretreatment of gold standard benzoyl peroxide therapy to kill resident facial bacterial, 11 weeks of daily topical application of NB01 will be evaluated.

Subject participation in the trial will approximately 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Double Blind Vehicle Controlled Trial, dual arm with 2:1 treatment to vehicle assignmentRandomized Double Blind Vehicle Controlled Trial, dual arm with 2:1 treatment to vehicle assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double blind
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Vehicle-Controlled Phase 1B Study of the Safety, Short-Term Engraftment and Action of NB01 in Adults With Moderate Acne
• Actual Study Start Date: Nov 1, 2018
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically.	Biological: NB01; 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
Placebo Comparator: Vehicle Control Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically.	Other: Vehicle Control; 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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Changes in Local Skin Reactions [Day 0 through day 80]

   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.

2. Number of Participants With Successful Follicular Engraftment of NB01 [12 weeks]

   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.

3. Absolute Change in Genotype Markers: Skin Surface Engraftment "Success" [Day 0 through day 80]

   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.

4. Absolute Change From Screening in Acne Lesion Counts [Day 0 through day 80]

   Reporting absolute change in counts.

5. Percent Change From Screening in Acne Lesion Counts [Day 0 through day 80]

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

6. Number of Participants Achieving "Success" on Investigator Global Assessment (IGA) [Day 0 through day 80]

   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.

7. Change in Acne QoL Questionnaire Score [Day 0 through day 80]

   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.

8. Absolute Change From Screening in Acne Lesion Counts: Outlier Censored [Day 0 through day 80]

   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.

9. Percent Change From Screening in Acne Lesion Counts: Outlier Censored [Day 0 through day 80]

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

10. Follicular Engraftment [12 weeks]

    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.

Secondary Outcome Measures

1. Absolute Change in Sebum Production. [Day 0 through day 80]

   Exploratory Endpoint: Absolute change from Baseline to week 12 in sebum production measured at the mid-glabellar region of the forehead using a Sebumeter.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has provided written informed consent.

2. Subject is male or non-pregnant female, 18-40 years of age, inclusive at Screening.

3. Subject has moderate facial acne vulgaris

4. Female subject with non-cyclical acne.

5. Women of childbearing potential (WOCBP) willing to use adequate contraception during study participation

6. Male subjects willing to use an acceptable method of contraception during study participation.

7. Subject has the ability to personally apply benzoyl peroxide (BPO) and study drug, as per protocol.

Exclusion Criteria:

1. Subject has active bacterial, viral, or fungal skin infections.

2. Subject has active nodulocystic acne or acne conglobate, acne fulminans, or other forms of acne (e.g., acne mechanica).

3. 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.

4. Subjects with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices/implantable devices/hardware.

5. Subject has a history of chronic human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infections.

6. Subject has a history of malignancy (with the exception of non-melanoma skin cancer).

7. Subject is immunosuppressed (such as resulting from transplantation, immunosuppressive therapy, active HIV infection/acquired immune deficiency syndrome [AIDS], neutropenia).

8. 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.

9. Subjects with close contacts (e.g., spouses, children, or members in the same household) that have severe skin barrier defects or are immunocompromised.

10. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	03	San Diego	California	United States	92123
2	01	Arlington	Texas	United States	76011
3	02	Austin	Texas	United States	78759

Sponsors and Collaborators

• Naked Biome, Inc.
• Therapeutics, Inc.

Investigators

• Study Director: Emma Taylor, MD, Naked Biome

Study Documents (Full-Text)

• Study Protocol - Jul 18, 2019
• Statistical Analysis Plan - Aug 15, 2019

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: Naked Biome, Inc.
• ClinicalTrials.gov Identifier: NCT03709654
• Other Study ID Numbers: NB01-P1BMA
• First Posted: Oct 17, 2018
• Last Update Posted: Aug 3, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Naked Biome, Inc.: acne; pimple; black head; white head; zit; probiotic
• Additional relevant MeSH terms: Acne Vulgaris

Study Results

Participant Flow

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Period Title: Overall Study
STARTED	23	13
COMPLETED	20	11
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Treatment Arm	Vehicle Control	Total
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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	Total of all reporting groups
Overall Participants	23	13	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (6.19)	24.6 (4.7)	24.4 (5.63)
Sex: Female, Male (Count of Participants)
Female	16 69.6%	8 61.5%	24 66.7%
Male	7 30.4%	5 38.5%	12 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 43.5%	7 53.8%	17 47.2%
Not Hispanic or Latino	13 56.5%	6 46.2%	19 52.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 8.7%	0 0%	2 5.6%
Asian	0 0%	1 7.7%	1 2.8%
Native Hawaiian or Other Pacific Islander	1 4.3%	0 0%	1 2.8%
Black or African American	3 13%	0 0%	3 8.3%
White	17 73.9%	12 92.3%	29 80.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	13 100%	36 100%
Investigator's Global Assessment (IGA) Score - Face (Score on scale) [Mean (Standard Deviation) ]
IGA at Screening	3 (0)	3 (0)	3 (0)
IGA at Baseline	3 (0)	3 (0)	3 (0)
Skin bacterial genotype (percentage of genotype) [Mean (Standard Deviation) ]
deoR/Panbac	21.8 (24.2)	26.0 (27.4)	23.3 (25.4)
Cas5/Panbac	7.3 (12.8)	7.8 (13.0)	7.5 (12.9)
Lesion Count (number of lesions) [Mean (Standard Deviation) ]
Inflammatory lesions	29.1 (7.3)	30.5 (5.6)	29.6 (6.7)
Non-Inflammatory lesions	35.9 (13.5)	37.4 (12.8)	36.4 (13.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Changes in Local Skin Reactions
Description	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.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

The Safety population included all randomized subjects who received and applied study drug.

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	21	12
Erythema: No Change / Improved	19 82.6%	11 84.6%
Erythema: Worsened	2 8.7%	1 7.7%
Edema: No Change / Improved	19 82.6%	9 69.2%
Edema: Worsened	2 8.7%	3 23.1%
Erosion/Ulceration: No Change / Improved	20 87%	12 92.3%
Erosion/Ulceration: Worsened	1 4.3%	0 0%
Scaling/Dryness: No Change / Improved	16 69.6%	11 84.6%
Scaling/Dryness: Worsened	5 21.7%	1 7.7%
Scabbing/Crusting: No Change / Improved	19 82.6%	12 92.3%
Scabbing/Crusting: Worsened	2 8.7%	0 0%
Itching: No Change / Improved	15 65.2%	11 84.6%
Itching: Worsened	6 26.1%	1 7.7%
Pain: No Change / Improved	20 87%	12 92.3%
Pain: Worsened	1 4.3%	0 0%

2. Primary Outcome

Title	Number of Participants With Successful Follicular Engraftment of NB01
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all randomized subjects who were dispensed the study drug and had at least 1 post-baseline assessment. Subjects were included in the treatment group to which they were randomized, regardless of the treatment received. All randomized subjects (N=36) were included in the mITT population.

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Count of Participants [Participants]	1 4.3%	0 0%

3. Primary Outcome

Title	Absolute Change in Genotype Markers: Skin Surface Engraftment "Success"
Description	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.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT)

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Genotype 1 (deoR), 2 weeks	6.9 (20.32)	2.5 (14.17)
Genotype 1 (deoR), 7 weeks	5.5 (17.63)	2.9 (16.96)
Genotype 1 (deoR), 12 weeks	3.9 (25.27)	14.9 (36.76)
Genotype 2 (Cas 5), 2 weeks	3.7 (8.16)	4.8 (12.56)
Genotype 2 (Cas 5), 7 weeks	6.6 (17.84)	3.9 (10.42)
Genotype 2 (Cas 5), 12 weeks	4.0 (10.32)	19.6 (38.69)

4. Primary Outcome

Title	Absolute Change From Screening in Acne Lesion Counts
Description	Reporting absolute change in counts.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT) population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Inflammatory Lesion Count: week 2	-4.3 (4.77)	-4.7 (6.8)
Inflammatory Lesion Count: week 7	-8.4 (6.64)	-6.7 (7.32)
Inflammatory Lesion Count: week 12	-15.5 (7.84)	-14.5 (9.56)
Non-Inflammatory Lesion Count: week 2	-1.9 (8.89)	-3.0 (6.30)
Non-Inflammatory Lesion Count: week 7	-8.6 (8.58)	-9.2 (8.52)
Non-Inflammatory Lesion Count: week 12	-15 (16.93)	-17.6 (10.66)

5. Primary Outcome

Title	Percent Change From Screening in Acne Lesion Counts
Description	Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT) population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Inflammatory Lesion Count: week 2	-15.8 (18.72)	-14.8 (20.1)
Inflammatory Lesion Count: week 7	-28.9 (20.72)	-20.0 (22.41)
Inflammatory Lesion Count: week 12	-54.8 (26.29)	-49.2 (27.19)
Non-Inflammatory Lesion Count: week 2	-5.8 (23.99)	-6.2 (16.09)
Non-Inflammatory Lesion Count: week 7	-25.0 (23.55)	-21.5 (17.93)
Non-Inflammatory Lesion Count: week 12	-43.5 (44.96)	-49 (23.84)

6. Primary Outcome

Title	Number of Participants Achieving "Success" on Investigator Global Assessment (IGA)
Description	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.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT) population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Success at 2 weeks	0 0%	0 0%
Success at 7 weeks	1 4.3%	0 0%
Success at 12 weeks	6 26.1%	1 7.7%

7. Primary Outcome

Title	Change in Acne QoL Questionnaire Score
Description	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.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT) population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	23	13
Mean (Standard Deviation) [score on a scale]	9.7 (16.2)	33.2 (23.65)

8. Primary Outcome

Title	Absolute Change From Screening in Acne Lesion Counts: Outlier Censored
Description	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.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

Ad Hoc Subject 02-005 (outlier) Censored mITT Population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	22	13
Inflammatory Lesion Count: week 2	-4.2 (4.82)	-4.7 (6.8)
Inflammatory Lesion Count: week 7	-8.5 (6.81)	-6.7 (7.32)
Inflammatory Lesion Count: week 12	-15.1 (7.79)	-14.5 (9.56)
Non-Inflammatory Lesion Count: week 2	-3.6 (2.77)	-3.0 (6.30)
Non-Inflammatory Lesion Count: week 7	-9.7 (7.35)	-9.2 (8.52)
Non-Inflammatory Lesion Count: week 12	-18 (10.31)	-17.6 (10.66)

9. Primary Outcome

Title	Percent Change From Screening in Acne Lesion Counts: Outlier Censored
Description	Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

Ad Hoc Subject 02-005 Censored mITT Population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	22	13
Inflammatory Lesion Count: week 2	-15.2 (18.91)	-14.8 (20.10)
Inflammatory Lesion Count: week 7	-29.0 (21.25)	-20.0 (22.41)
Inflammatory Lesion Count: week 12	-53.0 (25.72)	-49.2 (27.19)
Non-Inflammatory Lesion Count: week 2	-10.5 (8.55)	-6.2 (16.09)
Non-Inflammatory Lesion Count: week 7	-27.8 (20.18)	-21.5 (17.93)
Non-Inflammatory Lesion Count: week 12	-51.8 (26.42)	-49.0 (23.84)

10. Primary Outcome

Title	Follicular Engraftment
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT) population

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	20	11
Mean (Standard Deviation) [Percent increase Cas5]	6518.9 (6711.94)	492 (939.20)

11. Secondary Outcome

Title	Absolute Change in Sebum Production.
Description	Exploratory Endpoint: Absolute change from Baseline to week 12 in sebum production measured at the mid-glabellar region of the forehead using a Sebumeter.
Time Frame	Day 0 through day 80

Outcome Measure Data

Analysis Population Description

modified intent-to-treat subpopulation visiting a subset of sites with a Sebumeter.

Arm/Group Title	Treatment Arm	Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
Measure Participants	19	9
Mean (Standard Deviation) [μg/cm^2]	26.2 (52.48)	-22.9 (34.47)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Treatment Arm		Vehicle Control
Arm/Group Description	Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of NB01 probiotic applied topically. NB01: 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		Subjects will undergo 1 week lead-in with BPO followed by 11 weeks of vehicle applied topically. Vehicle Control: 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
All Cause Mortality
	Treatment Arm		Vehicle Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/13 (0%)
Serious Adverse Events
	Treatment Arm		Vehicle Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Arm		Vehicle Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		1/13 (7.7%)
General disorders
Application site dryness	2/23 (8.7%)	2	0/13 (0%)	0
Application site irritation	1/23 (4.3%)	1	0/13 (0%)	0
Influenza like illness	1/23 (4.3%)	1	0/13 (0%)	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/23 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Acne	1/23 (4.3%)	1	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.