Clinical trial NCT03151148: Targeted Microbiome Transplant in Atopic Dermatitis
Official title: A First in Man Evaluation of the Safety and Efficacy of an Allogeneic Targeted Microbiome Transplant in Adults With Moderate-to-Severe Atopic Dermatitis (ADRN-08)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Atopic Dermatitis (AD)
Keywords: allogeneic targeted microbiome transplant (TMT)
dysbiosis in AD
Staphylococcus aureus colonized skin
antimicrobial peptides (AMPs)
randomized trial
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Atopic Dermatitis Research Network
First posted: 2017-05-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the safety and effectiveness of a new therapy, commensal lotion containing infection fighting bacteria, on decreasing or eliminating the infection causing bacteria found on the skin of Atopic Dermatitis (AD) patients.

Detailed description: This study will enroll adult participants, 18-60 years of age, with moderate-to-severe atopic dermatitis (AD) and a positive Staphylococcus aureus (S. aureus) colonized lesion (at least 15 cm\^2 in size) on the upper extremities.

Participants who are eligible based on their positive Staph culture results will be randomized to one of two treatments: Targeted Microbiome Transplant Lotion (TMT) or Placebo (2:1 randomization). One lesional site measuring at least 15 cm\^2 and one non-lesional site of equal size will be identified on the participant's ventral upper extremities as the target swabbing areas. These sites will be photographed and marked for swabbing for reference at the participant's future visits. Participants will be instructed to apply investigational product with gloved hands to their ventral upper extremities bilaterally from the wrist to the upper humerus, which will include the identified lesional and non-lesional swabbing sites twice a day for 1 week starting on Day 0. Participants will return to clinic on Day 4 for the assessment of adverse events, the collection of skin swabs from the identified target sites, and to obtain additional investigational product and gloves. Participants will complete an additional clinic visit on Day 7 to correspond with the end of their 1 week treatment. During this visit, participants will be assessed for AEs and provide skin swab samples. All unused product and empty packets will be returned during the Day 4 and Day 7 visits. Three additional clinic visits on Days 8, 9, and 11 will be scheduled for additional skin swabs to assess the safety and the stability of the microbiome transplant and time to recurrence of Staph colonization. Participants will be followed through Day 38 to assess for safety and disease status.

Eligibility criteria: Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

* Participant must be able to understand and provide informed consent;
* Fulfills the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria (Appendix A) for active Atopic Dermatitis (AD);
* A Staphylococcus aureus (S. aureus) positive culture colonized lesion, at least 15 cm\^2 in size, located on a ventral upper extremity (e.g., arm);
* An Investigator Global Assessment (IGA) score, on the ventral arms, of at least moderate severity;
* A body surface area (BSA), as measured by Mosteller BSA Calculator, between 1.26 m\^2 (e.g., 4 feet, 10 inches and 85 pounds \[38.6 Kg\] and 2.25 m\^2 (e.g., 6 feet, 3 inches and 210 pounds \[95.5 Kg\]; and
* Females of childbearing potential who are willing to use adequate contraception 30 days prior to the Screening Visit and until participation in the study is complete.

  --Females of childbearing potential must agree to use an acceptable method of birth control (e.g. total abstinence, oral contraceptives, intrauterine device \[IUD\], barrier method with spermicide, surgical sterilization or surgically sterilized partner, Depo-Provera, Norplant, NuvaRing, or hormonal implants) for the duration of study participation.
* Male participants who are willing to use an acceptable method of contraception (e.g. barrier methods with spermicide, surgical sterilization or surgically sterilized partner) or practice abstinence until participation in the study is complete.

Exclusion Criteria:

* Inability or unwillingness of participant to give written informed consent or comply with study protocol;
* Pregnant or lactating females, or females who desire to become pregnant and/or breast feed within the duration of study participation;
* Active bacterial, viral, or fungal skin infections;
* Any noticeable breaks or cracks in the skin on the upper extremities, including severely excoriated skin or skin with open or weeping wounds suggestive of an active infection or increased susceptibility to infection;
* Sensitivity to or difficulty tolerating Dove fragrance-free bar soap, Cetaphil(R) Lotion, alcohol-based cleaners, macadamia nuts, soy, Vegetable glycerin, or palm kernels;
* Participants with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices;
* Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier;
* Any participant who is immunocompromised (e.g. history of lymphoma, Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS), Wiskott-Aldrich Syndrome) or has a history of malignant disease (with the exception of non-melanoma skin cancer);
* Participants with a history of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol;
* Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study;
* Ongoing participation in another investigational trial or use of investigational drugs within 8 weeks, or 5 half-lives (if known), whichever is longer, of the Screening Visit;
* Treatment with biologics within 16 weeks of Screening Visit;
* Participants with close contacts (e.g. spouses, children, or members in the same household) that have severe barrier defects or are immunocompromised;
* Use of topical (including steroids and calcineurin inhibitors) Atopic Dermatitis (AD) treatments within 7 days of the Treatment Visit; Use of topical steroids on areas outside of where investigational product is to be applied may be permitted, per investigator discretion;
* Treatment of AD with prescription moisturizers classified as medical device (e.g., Atopiclair®, MimyX®, Epicerum®, Cerave®, etc.) within 7 days of the Treatment Visit;
* Use of any oral or topical antibiotics within 7 days of the Treatment Visit;
* Participants who have taken a bleach bath within 7 days of the Treatment Visit;
* Use of any oral AD therapies (antihistamines, steroids, immunosuppressive therapies) within 28 days of the Treatment Visit; or
* Any phototherapy for skin disease (such as narrow band ultraviolet B \[NBUVB\], ultraviolet B \[UVB\], ultraviolet A1 \[UVA1\], psoralen + UVA \[PUVA\]) or regular use (more than 2 visits per week) of a tanning bed within 28 days of the Treatment Visit.

Primary outcomes:
measure: Per-Participant Daily Event Rate: Serious and Non-Serious Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 0 to Day 8
Secondary outcomes:
measure: The Occurrence of at Least One Serious or Non-Serious Treatment Emergent Adverse Event (TEAE)
timeFrame: Day 0 (after initiation of study treatment) through Day 8 (last day of study treatment)
measure: Per-Participant Daily Event Rate of Serious and Non-Serious Adverse Events (AEs)
timeFrame: Screening (up to 38 days before initiation of treatment) to Day 38 (last day of study participation)
measure: The Occurrence of at Least One Serious or Non-Serious Adverse Event (AE)
timeFrame: Screening (up to 38 days before initiation of treatment) to Day 38 (last day of study participation)
measure: The Eczema Area and Severity Index (EASI) Score of the Ventral Arms at Specific Days During the Measure Time Frame
timeFrame: Days 0, 4, 7, 8 and 11
measure: The Scoring Atopic Dermatitis (SCORAD) Score at Specific Days During the Measure Time Frame
timeFrame: Days 0, 4, 7, 8 and 11
measure: The Rajka-Langeland (RL) Score at Specific Days During the Measure Time Frame
timeFrame: Days 0 and 7
measure: The Pruritus Visual Analog Scale (VAS) Score of the Ventral Arms at Specific Days During the Measure Time Frame
timeFrame: Days 0, 4, 7, 8 and 11
measure: The Abundance of Coagulase Negative Staphylococcal (CoNS) Species, as Measured by Culture, on Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0, 4, 7, 8 and 11
measure: The Abundance of Coagulase Negative Staphylococcal (CoNS) Species, as Measured by qPCR (Quantitative Polymerase Chain Reaction), on Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: At days 0, 4, 7, 8 and 11
measure: The Change From Baseline Levels of Coagulase Negative Staphylococcal (CoNS) Bacteria Abundance, as Measured by Culture, on Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Change From Baseline Levels of Coagulase-Negative Staphylococcus (CoNS) Bacteria Abundance, as Measured by qPCR (Quantitative Polymerase Chain Reaction), on Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Change From Baseline Levels of S. Hominis A9 Bacteria Abundance, as Measured by Quantitative Polymerase Chain Reaction (qPCR), on Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of S. Aureus, as Measured by Culture, Between Treatment Groups on Lesional and Non-Lesional Skin Separately
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of S. Aureus, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of S. Aureus, as Measured by Culture, Between Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of S. Aureus, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Change From Baseline Levels of S. Aureus Abundance, as Measured by Culture, Between Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Change From Baseline Levels of S. Aureus Abundance, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Lesional and Non-Lesional Skin Within Each Treatment Group
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of Bacterial Deoxyribonucleic Acid (DNA) of Combined S. Hominis, as Measured by Quantitative Polymerase Chain Reaction (qPCR), Between Treatment Groups on Lesional and Non-Lesional Skin Separately
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of Bacterial Deoxyribonucleic Acid (DNA) of Combined Staphylococci, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
measure: The Abundance of Combined Bacterial Deoxyribonucleic Acid (DNA), as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately
timeFrame: Days 0 (1 hour post treatment), 4, 7, 8 and 11
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California - San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health General Clinical Research Center
state: Colorado
Study officials:
affiliation: University of California, San Diego: Dermatology Clinical Trials Unit
name: Richard Gallo, M.D., Ph.D.
role: STUDY_CHAIR
References:
citation: Nakatsuji T, Hata TR, Tong Y, Cheng JY, Shafiq F, Butcher AM, Salem SS, Brinton SL, Rudman Spergel AK, Johnson K, Jepson B, Calatroni A, David G, Ramirez-Gama M, Taylor P, Leung DYM, Gallo RL. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat Med. 2021 Apr;27(4):700-709. doi: 10.1038/s41591-021-01256-2. Epub 2021 Feb 22.