Atopic Dermatitis, Atopic Dermatitis Eczema
Conditions
Keywords
Dermatitis, Eczema
Brief summary
The goal of this study is to determine the safety and effects of ENS-002, a live biotherapeutic product (LBP) consisting of commensal, clonal, non-pathogenic bacteria in participants with atopic dermatitis.
Detailed description
This is a Phase 1, open-label, non-randomized, study investigating ENS-002, a live biotherapeutic product (LBP) consisting of commensal, clonal non-pathogenic bacteria The purpose of this dose escalation study is to determine the recommended Phase 2 dose (RP2D) of ENS-002 in participants with mild, moderate or severe atopic dermatitis. Participation in this study will continue until dose limiting toxicity or therapy intolerance, or participant withdrawal.
Interventions
BIOLOGICALENS-002
Live biotherapeutic product (LBP) consisting of commensal, clonal, non-pathogenic bacteria. Low Dose ENS-002 High Dose ENS-002
Sponsors
Concerto Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3 participants will be included in each of three cohorts of ENS-002.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand and sign an informed consent form (ICF). 2. Age 18 years or older on the day of signing the ICF. 3. Diagnosis of AD according to Hanifin and Rajka 4. Atopic dermatitis has been diagnosed and present for ≥ 6 months prior to the first planned ENS-002 administration. 5. EASI (Eczema Area and Severity Index) score of 5 to 7 (mild) or 7.1 to 21 (moderate), or ≥ 21.1 or severe at screening. 6. Mild, moderate or severe AD as scored by the IGA at screening and baseline For Cohort 1, in which only a single antecubital fossa or other body site lesion will be administered ENS-002, a target lesion IGA will be performed. 7. Body surface area involvement must be ≥ 2% for mild AD and \>10% for moderate to severe AD (excluding scalp, face, groin, and genitalia) at both screening and baseline as estimated based on the rule of nines and/or the palmar rule. Participants who have only one or a limited number of areas affected by AD (eg, neck, antecubital fossa, hands/feet, or popliteal involvement), as long as these sites have at least moderate severity, may also be eligible even if they do not meet the minimum BSA required - these participants will need to be approved by the Concerto Medical Monitor. 8. Presence of specific bacteria via qPCR. Two affected skin sites will be sampled as part of the screening tests; if at least one of the affected skin sites contains the specified bacteria, the participant is eligible pending eligibility in all the other inclusion/
Exclusion criteria
. If the qPCR test does not detect the specified bacteria, the participant is not eligible, but the bacteria skin swabs may be repeated. No more than 2 attempts to detect the specified bacterial colonization over 28 days may be made. 9. Acceptable screening laboratory values that are within normal limits or are not clinically significantly abnormal. If clinical significance is unclear, the investigator must consult with Concerto's medical monitor. * Complete blood count with WBC differential (including absolute values). * Chemistry panel including hepatic transaminases. * CRP. * Urinalysis. * 12-lead electrocardiogram. * For women of childbearing potential (WOCBP), serum and/or urine test consistent with a non-pregnant state. 10. If using an oral and/or topical H1 antihistamine for pruritus and/or insomnia, must have been on a stable dose and frequency for at least 14 days prior to screening and must continue at the same dose and frequency throughout the study. 11. Willing and able to complete once-daily electronic diary entries for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of ENS-002 total doses | Up to 43 days | Incidence of adverse events after applying different total doses of ENS-002 as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Safety of ENS-002 dose frequency | Up to 43 days | Incidence of adverse events after applying different dose frequencies of ENS-002 as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Safety of ENS-002 different dose durations | Up to 43 days | Incidence of adverse events after applying different dose durations of ENS-002 as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Tolerability of ENS-002 total doses | Up to 43 days | Evaluate the tolerability of different total doses of ENS-002 administration as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Tolerability of ENS-002 different dose frequencies | Up to 43 days | Evaluate the tolerability of different dose frequencies of ENS-002 administration as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Tolerability of ENS-002 different dose durations | Up to 43 days | Evaluate the tolerability of different dose durations of ENS-002 administration as measured by clinical laboratory tests, vital signs and physical examination at end of treatment compared to baseline |
| Recommended Phase 2 Dose (RP2D) | Up to 43 days | Evaluate the safety of applying different total doses, dose frequencies, and durations of ENS-002 administration to determine a tentative recommended Phase 2 dose (RP2D). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ENS-002 Administration Compliance recorded in ePRO diary | Up to 14 days | Assess compliance of actual ENS-002 administrations by directed questions as recorded in an electronic participant reported outcome (ePRO) diary. |
| Severity of Pruritus Scale (SPS) pruritus | Up to 43 days | Determine effects of ENS-002 on pruritus by absolute and mean changes in SPS at end of treatment compared to baseline |
| Severity of Pruritus Scale (SPS) affected skin | Up to 43 days | Determine effects of ENS-002 on affected skin area by absolute and mean changes in SPS at end of treatment compared to baseline |
| Severity of Pruritus Scale (SPS) severity | Up to 43 days | Determine effects of ENS-002 on severity by absolute and mean changes in SPS at end of treatment compared to baseline |
| Eczema Area and Severity Index (EASI) affected skin | Up to 43 days | Determine effects of ENS-002 on affected skin area by absolute change and percent of participants with a ≥ 50%, ≥ 75%, or ≥ 90% reduction in EASI at end of treatment compared to baseline |
| Eczema Area and Severity Index (EASI) severity | Up to 43 days | Determine effects of ENS-002 on severity by absolute change and percent of participants with a ≥ 50%, ≥ 75%, or ≥ 90% reduction in EASI at end of treatment compared to baseline |
| Investigator Global Assessment (IGA) 0 to 1 | Up to 43 days | Determine percent of participants with an Investigator Global Assessment (IGA) of 0 or 1 at end of treatment compared to baseline |
| Investigator Global Assessment (IGA) absolute decrease of at least 2 points | Up to 43 days | Determine percent of participants with an absolute decrease of at least 2 points for moderate atopic dermatitis (AD) in Investigator Global Assessment (IGA) at end of treatment compared to baseline |
| Body Surface Area (BSA) absolute change | Up to 43 days | Absolute change from baseline in percent BSA affected |
| Body Surface Area (BSA) mean change | Up to 43 days | Mean change from baseline in percent BSA affected |
| Changes in corticosteroid use by participants | Up to 43 days | Determine type, potency and frequency of corticosteroid use |
| Changes in corticosteroid use for flares | Up to 43 days | Determine number of participants resorting to corticosteroids for flares. |
| ENS-002 Administration Compliance - percentage of planned administrations | Up to 14 days | Assess compliance of actual ENS-002 administrations as a percentage of planned administrations determined by counting used and unused vials and asking participants |
| Levels of specified bacterial colonization on affected skin | Up to 43 days | Measure levels of specified bacterial colonization on affected skin by quantitative polymerase chain reaction (qPCR). |
| Levels of specified bacterial colonization on non-affected skin | Up to 43 days | Measure levels of specified bacterial colonization on non-affected skin at end of treatment compared to baseline by quantitative polymerase chain reaction (qPCR). |
| ENS-002 skin colonization | Up to 43 days | Measure extent of ENS-002 skin colonization at end of treatment compared to baseline quantitative by polymerase chain reaction (qPCR). |
| Peak Pruritus Numerical Rating Scale (PPNRS) pruritus | Up to 43 days | Determine effects of ENS-002 on pruritus by absolute and mean changes in PPNRS at end of treatment compared to baseline |
| Peak Pruritus Numerical Rating Scale (PPNRS) affected skin | Up to 43 days | Determine effects of ENS-002 on affected skin area by absolute and mean changes in PPNRS at end of treatment compared to baseline |
| Peak Pruritus Numerical Rating Scale (PPNRS) severity | Up to 43 days | Determine effects of ENS-002 on severity by absolute and mean changes in PPNRS at end of treatment compared to baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in WBC subsets in peripheral blood | Up to 43 days | Assess blood samples for changes in WBC subsets (eg, neutrophils, lymphocytes) after ENS-002 administration |
| Changes in C-Reactive Protein (CRP) in peripheral blood | Up to 43 days | Assess blood samples for changes in CRP after ENS-002 administration |
| Changes in immune cells in peripheral blood | Up to 43 days | Assess blood samples for changes in immune cells after ENS-002 administration |
| Changes in cytokines in peripheral blood | Up to 43 days | Assess blood samples for changes in cytokines after ENS-002 administration |
| Changes in immunoglobulin E (IgE) in peripheral blood | Up to 43 days | Assess blood samples for changes in immunoglobulin E (IgE) after ENS-002 administration |
| Changes in chemokines in peripheral blood | Up to 43 days | Assess blood samples for changes in chemokines after ENS-002 administration |
| Changes in skin inflammatory markers | Up to 43 days | Skin tape strips will be taken to assess changes in immune markers including cytokines and chemokines after ENS-002 administration |
| Microbiome changes on affected skin not administered ENS-002. Microbiome changes on affected and non-affected skin. | Up to 43 days | Skin swabs to evaluate microbiome changes on affected skin that was not administered ENS-002 |
| Microbiome changes on affected skin administered ENS-002. Microbiome changes on affected and non-affected skin. | Up to 43 days | Skin swabs to evaluate microbiome changes on affected skin that was administered ENS-002 |
| Microbiome changes on non-affected skin Microbiome changes on affected and non-affected skin. | Up to 43 days | Skin swabs to evaluate microbiome changes on non-affected skin |
| Participant preferences and feedback on feasibility and tolerability of ENS-002 administration. | Up to 43 days | Collect Electronic participant reported outcomes (ePRO). The ePRO diary will include specific questions on skin color change, pruritus, rash, pain, tenderness, fever, chills, night sweats, and other side effects, along with ease of application, skin feel, interference with use of emollients or other topically applied agents, effect on usual hygiene practices, residual feel after dosing has stopped, and effect on activities of daily living (eg, sleep, exercise, wearing clothing). |
| Changes in White Blood Count (WBC) in peripheral blood | Up to 43 days | Assess blood samples for changes in white blood cell (WBC) count after ENS-002 administration |
Countries
United States
Outcome results
None listed