Study NCT03018275
Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis
Submitted Date:  February 25, 2021 (v41)
Quality Control Review Has Not Concluded

Note: The results information displayed below has not completed the quality control (QC) review process. ClinicalTrials.gov must post results information for applicable clinical trials (ACTs) within 30 days of submission, even if the submission has not completed the QC review process. The study sponsor or investigator is responsible for ensuring the results information meets the QC review criteria.

This submission includes brief standardized QC review comments added by the National Library of Medicine (NLM). These comments indicate the location of apparent errors, deficiencies, or inconsistencies. For more information, see the Final Rule (42 CFR Part 11) Information page.


General Comments

Quality Control Review Comment provided by the National Library of Medicine:

  1. Issues noted on a previous submission of this record do not appear to have been addressed.
Open or close this module Study Identification
Unique Protocol ID: 170033
Brief Title: Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis
Official Title: Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis Phase I/II
Secondary IDs: 17-I-0033
Open or close this module Study Status
Record Verification: October 2019
Overall Status: Completed
Study Start: April 20, 2017
Primary Completion: October 11, 2019 [Actual]
Study Completion: October 11, 2019 [Actual]
First Submitted: January 11, 2017
First Submitted that
Met QC Criteria:
January 11, 2017
First Posted: January 12, 2017 [Estimate]
Results First Submitted: June 9, 2020
Results First Submitted that
Met QC Criteria:
Results First Posted: March 17, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: March 17, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary:

Background:

Atopic dermatitis (AD) is a skin disease also called eczema. It is common in children and sometimes gets better on its own. However, chronic AD may cause asthma, food allergies, eye infections, and sleep problems. The cause of AD might be related to bacteria that live on the skin. Researchers want to see if introducing bacteria, R mucosa, from healthy skin onto the skin of someone with AD helps treat the disease.

Objective:

To test the safety and activity of R mucosa for treating AD.

Eligibility:

Part 1: People ages 18 and older with AD

Part 2: Children ages 3-17 with AD

Design:

Participants will be screened with:

Medical history

Physical exam

Examination of their AD

Blood and urine tests

At the baseline visit, participants will have blood tests and photos taken of their skin. They will get a supply of R mucosa and a memory aid to track their doses and record how they are feeling. Part 2 participants guardians will complete questionnaires about their child s AD.

Part 1 participants will spray R mucosa on their arm twice per week for 6 weeks.

Part 2 guardians will spray it on their child s arm twice per week for 16 weeks.

Participants will have follow-up visits to repeat some baseline tests and review their memory aid:

Part 1: Six weeks after the baseline visit

Part 2: Four times over 16 weeks; then 2 or 3 times for 1 year

Participants will be called or emailed to discuss how they are feeling:

Part 1: About 30 days after their last visit

Part 2: About every 10 days between visits

Detailed Description: The underlying pathology of atopic dermatitis (AD) consists of defective skin barrier function, susceptibility to Staphylococcus aureus skin infection, and immune imbalance. There is currently no cure for AD. Preclinical data in a mouse model of AD suggest that commensal Gram-negative bacteria (CGN), such as Roseomonas mucosa, from a healthy source can relieve symptoms of AD and have antimicrobial effects. In this study, we will first evaluate the safety of R mucosa-based biotherapy in adults with AD (age 18+ years; part 1), and then evaluate the safety and activity of R mucosa-based biotherapy in children (ages 3-17 years) with AD (parts 2A and 2B). In part 1, participants will receive twice-weekly doses of CGN biotherapy for 6 weeks, with dose escalations at 2 and 4 weeks. In part 2, participants will receive twice-weekly doses of CGN biotherapy for 4 months, with possible dose escalations at 4 and 8 weeks (part 2A only). Starting at 12 weeks for both parts 2A and 2B, dosing frequency may be increased to every other day. Participants in part 1 will be contacted 30 10 days after end of treatment for assessment of safety. Participants in parts 2A and 2B will also be followed for up to 1 year after the end of treatment for evaluation of long-term activity and safety. This will be the first study to test cutaneous live biotherapeutic products for AD. We hypothesize that altering the strains of CGN on the skin of people with AD will improve the patient s clinical outcome. We do not expect serious toxicities because R mucosa is rarely pathogenic; reported cases of bacteremia have typically been associated with percutaneous catheters in immunocompromised patients, who are excluded from this study.
Open or close this module Conditions
Conditions: Atopic Dermatitis
Keywords: Lyophilized Biotherapeutic, Microbiome, Probiotic
Commensal Gram-negative Bacteria
Staphylococcus Aureus
Transepidermal Water Loss
Allergic Diseases
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 31 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part 1: adults and young adults, aged 18+ years
Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)
Biological: Roseomonas mucosa
R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.
Experimental: Part 2A: children, aged 9-17 years
Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)
Biological: Roseomonas mucosa
R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.
Experimental: Part 2B: children, aged 3-17 years
Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)
Biological: Roseomonas mucosa
R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Reduction in SCORAD
[ Time Frame: 1 year ]

SCORAD ia a measure of eczema severity including rash, itch severity, and sleep disturbance. The primary outcome was a 50% reduction in antecubital-specific SCORing Atopic Dermatitis (SCORAD) with no adverse events related to product use. Frequency of solicited adverse events, unsolicited adverse events, serious adverse events, and death.
Secondary Outcome Measures:
1. A 30% Improvement in the Quality of Life as Measured by the Validated Children's Dermatology Life Quality Index (CDLQI)
[ Time Frame: 16 weeks ]

CDLQI is a measurement of how burdensome the disease is on the child. Lower numbers mean less disruption in their life.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
2. A 30% Improvement in the Quality of Life as Measured by the Validated Family Dermatology Life Quality Index (FDLQI)
[ Time Frame: 16 weeks ]

FDLQI is a measure of how burdensome the disease is on families

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Open or close this module Eligibility
Minimum Age: 3 Years
Maximum Age: 99 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:
  • INCLUSION CRITERIA:

Inclusion Criteria for Young Adults and Adults with AD (Part 1)

  1. Age 16+ years
  2. SCORAD of at least 10
  3. Have a clinical diagnosis of AD with active involvement of the antecubital fossa
  4. Willing to allow storage of blood for future research
  5. No history of other skin disease
  6. Initiated or attempted standard of care therapy at least 6 months prior to enrollment
  7. Must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) when engaging in sexual activities that can result in pregnancy. The effects of CGN live biotherapy on the developing human fetus are unknown. Adequate contraception must be used consistently, beginning before the first dose and lasting for the duration of study participation. Participants of childbearing potential must have a negative pregnancy test result before they receive CGN live biotherapy. During the course of the study, if a participant becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately.

Inclusion Criteria for Children with AD (Part 2)

  1. Age 3-16 years
  2. SCORAD of at least 10
  3. Have a clinical diagnosis of AD with active involvement of the antecubital fossa
  4. Willing to allow storage of blood and bacterial swabs for future research
  5. Initiated or attempted standard of care therapy at least 6 months prior to enrollment
  6. Participants who have begun menstruating must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) when engaging in sexual activities that can result in pregnancy.

EXCLUSION CRITERIA:

  1. Presence of an indwelling venous or arterial catheter
  2. Individuals living with anyone with a diagnosed immunodeficiency, cardiac valvular disease, and/of indwelling catheter
  3. Precence of allergies to aimkacin, ciprofloxacin, gentamicin, levofloxacin, and tobramycin (which would preclude treatment of any unexpected infection)
  4. History of cardiac valvular disease
  5. Any history of grade 2 or higher neutropenia or leukopenia
  6. Clinical suspicion of immunodeficiency, liver disorder, kidney disorder, and/or HIV
  7. Pregnant or breastfeeding
  8. Any history of anti-TNF treatment
  9. Inability to demonstrate proper bacteria administration procedure despite coaching and training
  10. Use of fluoroquinolone or aminoglycoside antibiotics within 2 weeks of enrollment
  11. Any condition that, in the opinion of the investigator, contraindicates participation in this Study

Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the investigator.

Open or close this module Contacts/Locations
Study Officials: Ian A Myles, M.D.
Principal Investigator
National Institute of Allergy and Infectious Diseases (NIAID)
Locations: United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: Boguniewicz M, Leung DY. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol. 2010 Jan;125(1):4-13; quiz 14-5. doi: 10.1016/j.jaci.2009.11.027. Review. PubMed 20109729
Myles IA, Williams KW, Reckhow JD, Jammeh ML, Pincus NB, Sastalla I, Saleem D, Stone KD, Datta SK. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016 Jul 7;1(10). pii: 86955. doi: 10.1172/jci.insight.86955. PubMed 27478874
Bantz SK, Zhu Z, Zheng T. The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma. J Clin Cell Immunol. 2014 Apr;5(2). pii: 202. PubMed 25419479
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol, Statistical Analysis Plan, and Informed Consent Form
Document Date: May 6, 2019
Uploaded: 06/08/2020 15:52
File Name: Prot_SAP_ICF_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Adults Children 9-17 Years of Age Children Age 3-17 Years
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Treatment with R mucosa at 10^3, 10^4, and 10^5 CFU/mL Treatment with R mucosa at 10^3, 10^4, and 10^5 CFU/mL
Period Title: Overall Study
Started 10 5 16
Completed 10 5 15
Not Completed 0 0 1
Reason Not Completed
Withdrawal by Subject 0 0 1
Open or close this module Baseline Characteristics
Arm/Group TitleAdultsChildren 9-17 Years of AgeChildren Age 3-17 YearsTotal
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Total of all reporting groups
Overall Number of Baseline Participants 10 5 16 31
Baseline Analysis Population Description
Age, Categorical
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed10 Participants5 Participants16 Participants31 Participants
<=18 years
0
0%
5
100%
16
100%
21
67.74%
Between 18 and 65 years
8
80%
0
0%
0
0%
8
25.81%
>=65 years
2
20%
0
0%
0
0%
2
6.45%
Age, Continuous
Mean (Full Range)
Unit of measure: years
Number Analyzed10 Participants5 Participants16 Participants31 Participants
23(18 to 70)11(9 to 14)7(3 to 15)19(2 to 70)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed10 Participants5 Participants16 Participants31 Participants
Female
9
90%
3
60%
7
43.75%
19
61.29%
Male
1
10%
2
40%
9
56.25%
12
38.71%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed10 Participants5 Participants16 Participants31 Participants
Hispanic or Latino
0
0%
2
40%
1
6.25%
3
9.68%
Not Hispanic or Latino
10
100%
3
60%
15
93.75%
28
90.32%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed10 Participants5 Participants16 Participants31 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
2
20%
1
20%
1
6.25%
4
12.9%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
2
12.5%
2
6.45%
White
8
80%
3
60%
13
81.25%
24
77.42%
More than one race
0
0%
1
20%
0
0%
1
3.23%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed10 Participants5 Participants16 Participants31 Participants
United States
1051530

Quality Control Review Comment provided by the National Library of Medicine:

  1. Results information appears incomplete.
Open or close this module Outcome Measures
1. Primary Outcome:
Title Reduction in SCORAD
Description SCORAD ia a measure of eczema severity including rash, itch severity, and sleep disturbance. The primary outcome was a 50% reduction in antecubital-specific SCORing Atopic Dermatitis (SCORAD) with no adverse events related to product use. Frequency of solicited adverse events, unsolicited adverse events, serious adverse events, and death.
Time Frame 1 year
Outcome Measure Data
Analysis Population Description
The majority of patients experienced a 50% reduction in SCORAD (a measure of eczema severity) without related adverse events.
 
Arm/Group TitleAdultsChildren 9-17 Years of AgeChildren 3-17 Years of Age
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

R mucosa at 10^3, 10^4, and 10^5 CFU/mLR mucosa 10^3, 10^4, and 10^5 CFU/mL
Overall Number of Participants Analyzed10 5 15
Measure Type: Count of Participants
Unit of Measure: Participants
10
100%
5
100%
15
100%

Quality Control Review Comment provided by the National Library of Medicine:

  1. A free-text field appears to include results data or conclusions drawn from the data. All results data must be reported in a tabular format.
  2. One or more numbers in the table appear to be nonmeaningful placeholders that do not reflect data collected during the study.
2. Secondary Outcome:
Title A 30% Improvement in the Quality of Life as Measured by the Validated Children's Dermatology Life Quality Index (CDLQI)
Description CDLQI is a measurement of how burdensome the disease is on the child. Lower numbers mean less disruption in their life.
Time Frame 16 weeks

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Outcome Measure Data
Analysis Population Description
Most families noted a significant improvement in their quality of life
 
Arm/Group TitleAdultsChildren 9-17 Years OldChildren 3-17 Years of Age
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

R mucosa 10^3, 10^4, and 10^5 CFU/mLR mucosa 10^3, 10^4, and 10^5 CFU/mL
Overall Number of Participants Analyzed0 5 10
Mean (Standard Deviation)
Unit of Measure: Points improvement
6(1.5) 5(1.7)

Quality Control Review Comment provided by the National Library of Medicine:

  1. A free-text field appears to include results data or conclusions drawn from the data. All results data must be reported in a tabular format.
3. Secondary Outcome:
Title A 30% Improvement in the Quality of Life as Measured by the Validated Family Dermatology Life Quality Index (FDLQI)
Description FDLQI is a measure of how burdensome the disease is on families
Time Frame 16 weeks

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Outcome Measure Data
Analysis Population Description
improvement in quality of life measures for both the patients (52%) and families (58.4%)
 
Arm/Group TitleAdultChildren 9-17 Years OldChildren 3-17 Years Old
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Overall Number of Participants Analyzed0 5 15
Mean (Standard Deviation)
Unit of Measure: Points improved
8(2.1) 8(1.7)

Quality Control Review Comment provided by the National Library of Medicine:

  1. Required information appears to be missing.
  2. A free-text field appears to include results data or conclusions drawn from the data. All results data must be reported in a tabular format.
Open or close this module Adverse Events
 
Time Frame 1 year
Adverse Event Reporting Description As in clinical trials.gov, all AE for the year in the study were reported
 
Arm/Group Title Adult Children 9-17 Years Old Children 3-17 Years Old
Arm/Group Description

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)

Roseomonas mucosa: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.

All-Cause Mortality
  AdultChildren 9-17 Years OldChildren 3-17 Years Old
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 10 (0%)0 / 5 (0%)0 / 16 (0%)
Serious Adverse Events
  AdultChildren 9-17 Years OldChildren 3-17 Years Old
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 10 (0%)0 / 5 (0%)0 / 16 (0%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
  AdultChildren 9-17 Years OldChildren 3-17 Years Old
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 10 (0%)0 / 5 (0%)0 / 16 (0%)
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact:
Name/Official Title:
Dr Ian A Myles
Organization:
NIH
Phone:
301-451-8420
Email:
Mylesi@nih.gov

Scroll to the Study top