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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Number of Participants With Changes in Local Skin Reactions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
Number of Participants With Changes in Local Skin Reactions
时间窗: 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.
Change in Acne QoL Questionnaire Score
时间窗: 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.
Absolute Change in Genotype Markers: Skin Surface Engraftment "Success"
时间窗: 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.
Percent Change From Screening in Acne Lesion Counts
时间窗: Day 0 through day 80
Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)
Absolute Change From Screening in Acne Lesion Counts: Outlier Censored
时间窗: 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.
Percent Change From Screening in Acne Lesion Counts: Outlier Censored
时间窗: Day 0 through day 80
Efficacy endpoint: Percent change from Screening lesion counts at Day 80 (end of treatment)
Follicular Engraftment
时间窗: 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.
Number of Participants With Successful Follicular Engraftment of NB01
时间窗: 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.
Absolute Change From Screening in Acne Lesion Counts
时间窗: Day 0 through day 80
Reporting absolute change in counts.
Number of Participants Achieving "Success" on Investigator Global Assessment (IGA)
时间窗: 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.
次要结局
- Absolute Change in Sebum Production.(Day 0 through day 80)