Topical ENS-002 for Atopic Dermatitis in Adults

Atopic Dermatitis Clinical Trial

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Official title:

Phase 1 First in Human Dose Escalation and Safety Study of Topical ENS-002 for Atopic Dermatitis in Adults

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06469385
• Other study ID #: ENS-002-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 10, 2024
• Est. completion date: December 20, 2024

Study information

• Verified date: June 2024
• Source: Concerto Biosciences
• Contact: Barb Geiger, BSN
• Phone: 913-206-2798
• Email: barb[@]concertobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to determine the safety and effects of ENS-002, a live biotherapeutic product (LBP) consisting of 3 distinct commensal, clonal, non-pathogenic bacteria in participants with atopic dermatitis.

Description:

This is a Phase 1, open-label, non-randomized, study investigating ENS-002, a live biotherapeutic product (LBP) consisting of 3 distinct commensal, clonal, non-pathogenic bacteria that reduces growth of Staph Aureus on the skin. The purpose of this dose escalation study is to determine the recommended Phase 2 dose (RP2D) of ENS-002 in participants with mild to moderate atopic dermatitis. Participation in this study will continue until dose limiting toxicity or therapy intolerance, or participant withdrawal.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: December 20, 2024
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) at screening.

6. Mild-to-moderate AD as scored by the IGA at screening and baseline For Cohort 1, in which only a single antecubital fossa lesion will be administered ENS-002, a target lesion IGA will be performed, and the ventral arm site must have an IGA score of at least moderate severity (ie, IGA of at least 3).

7. Body surface area involvement must be = 5% and = 40% for mild-to-moderate 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 antecubital fossa or popliteal involvement, as long as they have moderate severity, may also be eligible - these participants will need to be approved by the Concerto medical monitor.

8. Presence of S. aureus colonization 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 S. aureus, the participant is eligible pending eligibility in all the other inclusion/exclusion criteria. If the qPCR test does not detect S. aureus, the participant is not eligible, but the S. aureus skin swabs may be repeated. No more than 2 attempts to detect S. aureus colonization over 14 days may be made.

9. Acceptable screening laboratory values that are within normal limits or are not clinically significantly abnormal (Table 7). 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.

Exclusion Criteria:

1. Severe AD (EASI = 21.1).

2. Has only facial AD.

3. Has more than 20 GBSA if to be enrolled into Cohort 2 or more than 10 GBSA if to be enrolled in Cohort 3 that are affected by AD (See GBSA Figure 2). These GBSA restrictions exclude face, scalp, genitalia, and groin lesions.

4. Presence of non-AD dermatologic disorder(s) including, but not limited to, the following dermatitides: photodermatitis, allergic contact, infestations (including scabies), eczematous eruption (eg, secondary to calcium channel blockers), nummular, stasis, dermatitis herpetiformis, xerotic, widespread seborrheic, bullous pemphigoid (prodromal phase), eczematous psoriasis, or mycosis fungoides (Sezary syndrome).

5. Presence of idiopathic chronic eczematous eruption of aging - defined as new-onset, atopic-like dermatitis presenting in people > 50 years old with no history of childhood AD.

6. Presence of indwelling arterial or venous catheters.

7. Cardiac valve disease history or artificial valve or pacemaker in place.

8. Implanted devices/prostheses including, but not limited to, eye lens, knee, hip, etc. replacements.

9. History of Grade 2 or higher neutropenia or leukopenia (except for known benign neutropenia typical for Fy(a-b-) status [formerly known as benign ethnic neutropenia or BEN]).

10. Unwilling to stop hair removal by any method (including shaving, waxing, or depilatory creams) in ENS-002 administration body sites for 7 days prior to the first ENS-002 administration and for at least 7 days after the last ENS-002 administration.

11. Any significant breaks or cracks in the skin in the target areas of ENS-002 administration, including severe excoriations or open or weeping wounds suggestive of an active infection/increased susceptibility to infection.

12. Clinically significant immunodeficiency (congenital or acquired [including a history of treated or untreated HIV, malnutrition, chronic viral infection]).

13. Netherton syndrome or other genodermatoses resulting in a defective epidermal barrier.

14. Active malignancy or history of malignancy in the past 3 years (Exceptions:

superficial skin cancers - squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only and indolent prostate cancer).

15. Clinically significant cardiovascular, liver, pulmonary, neurologic, metabolic, or kidney disease or any other comorbid medical, surgical, social, or psychiatric condition, that, in the opinion of the investigator, puts the participant at increased risk, might lead to study noncompliance, and/or confounds interpretation of safety and efficacy data.

16. Required to take immunosuppressive drugs (eg, including but not limited to chemotherapy, systemic corticosteroids [= 10 mg prednisone equivalent/day; allowed corticosteroids: inhaled, intra-articular, topical, or if systemic, permitted at doses intended only for adrenal replacement, or if = 5 days prior to first ENS-002 administration, on a one-time basis as a prophylaxis for imaging procedures], anti-tumor necrosis factor, colchicine, hydroxychloroquine, sulfasalazine, dapsone, methotrexate, mycophenylate mofetil, azathioprine, anti-interleukin-6 (anti-IL-6) antibody, anti-IL-1 antibody, or anti-CD20 antibody). If uncertain, contact the Concerto medical monitor for approval/guidance.

17. Lives with or has frequent contact with individual(s) with implantable medical devices including, but not limited to, artificial eye lens, artificial joint, cardiac stents, indwelling venous or arterial catheters, cardiac valvular disease, or artificial valve in place; or who have severe skin barrier defects or known immunodeficiency (congenital or acquired [eg, treated or untreated HIV, malnutrition, chronic viral infections]). If there is any question on this exclusion criterion contact the Concerto medical monitor.

18. Received oral or systemic antibiotics within 21 days prior to screening.

19. Inability to tolerate > 7 days without topical AD treatments and topical antibiotics (prescription or over-the-counter [OTC]) or has had topical antibiotics = 7 days prior to screening.

20. Therapy prior to the first planned dose of ENS-002 with one or more of the following:

systemic corticosteroids (within 28 days) or topical corticosteroids (low or mid-potency within 14 days; high potency within 28 days), topical phosphodiesterase inhibitors (within 7 days), or emollients (within 7 days) other than those emollients allowed in this study (Table 5). If a participant has used a product with a 7-, 14-, or 28-day eligibility limit, a minimum of a 7-, 14-, or 28-day washout, respectively, is required before the first planned dose of ENS-002.

21. Treatment with systemic therapies with anti-pruritic (eg, tricyclic antidepressants, sedatives, tranquilizers, marijuana or other cannabinoids, opioid receptor agonists/antagonists) or pruritus-inducing (eg, opioids, angiotensin-converting enzyme inhibitors, cocaine, antimalarials) potential within 28 days prior to the first planned dose of ENS-002.

22. Therapy within 28 days prior to the first planned dose of ENS-002 with any immuno-modulating agents (eg, cyclosporine, azathioprine, methotrexate), phototherapy, or indoor tanning.

23. Therapy within 56 days or 5 half-lives (whichever is longer) prior to the first planned dose of ENS-002 with investigational drugs or any Janus kinase inhibitors (JAKs).

24. Therapy with dupilumab within 112 days (16 weeks) or 5 half-lives (whichever is longer) prior to the first planned dose of ENS-002.

25. Bleach baths within 30 days prior to the first planned dose of ENS-002.

26. Use of any live topical bacterial product (OTC products within 4 weeks or investigational bacteria within 365 days) prior to the first planned dose of ENS-002.

27. Allergic to any of the excipients in ENS-002 (pea hydrolysate, potassium phosphate dibasic, sodium chloride, yeast extract, water for injection, glycerol, and methylcellulose).

28. Unable to use at least 2 of the 6 rescue antibiotics that cover all 3 bacteria in ENS-002 (Table 12).

29. Pregnant or planning to attempt to become pregnant during this study, breast feeding, breast pumping, or planning to breast feed.

30. Participant with a pregnant or breastfeeding partner or a partner planning to attempt to become pregnant during the study.

31. Unable to demonstrate proper ENS-002 application technique despite proficiency training.

32. Any prior exposure to ENS-002.

33. Is biologically a WOCBP; eg, has not had a hysterectomy, has not been in menopause for at least one year, and cannot or is unable or unwilling to use highly effective birth control measures (Section 13.2.4) during this study and for 90 days after the last administration of ENS-002.

34. If biologically male and fertile, cannot donate sperm and must adhere to highly effective birth control measures (Section 13.2.4) during this study and for 90 days after the last administration of ENS-002.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Atopic Dermatitis Eczema
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Biological:
• ENS-002
Live biotherapeutic product (LBP) consisting of 3 distinct commensal, clonal, non-pathogenic bacteria. Dose Levels of ENS-002 (CFU) 1 x 10 7 CFU ENS-002 1 x 10 8 CFU ENS-002 1 x 10 8 CFU ENS-002

Locations

Country	Name	City	State
United States	Derm Research	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Concerto Biosciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in White Blood Count (WBC) in peripheral blood	Assess blood samples for changes in white blood cell (WBC) count after ENS-002 administration	Up to 43 days
Other	Changes in WBC subsets in peripheral blood	Assess blood samples for changes in WBC subsets (eg, neutrophils, lymphocytes) after ENS-002 administration	Up to 43 days
Other	Changes in C-Reactive Protein (CRP) in peripheral blood	Assess blood samples for changes in CRP after ENS-002 administration	Up to 43 days
Other	Changes in immune cells in peripheral blood	Assess blood samples for changes in immune cells after ENS-002 administration	Up to 43 days
Other	Changes in cytokines in peripheral blood	Assess blood samples for changes in cytokines after ENS-002 administration	Up to 43 days
Other	Changes in immunoglobulin E (IgE) in peripheral blood	Assess blood samples for changes in immunoglobulin E (IgE) after ENS-002 administration	Up to 43 days
Other	Changes in chemokines in peripheral blood	Assess blood samples for changes in chemokines after ENS-002 administration	Up to 43 days
Other	Changes in skin inflammatory markers	Skin tape strips will be taken to assess changes in immune markers including cytokines and chemokines after ENS-002 administration	Up to 43 days
Other	Microbiome changes on affected skin not administered ENS-002. Microbiome changes on affected and non-affected skin.	Skin swabs to evaluate microbiome changes on affected skin that was not administered ENS-002	Up to 43 days
Other	Microbiome changes on affected skin administered ENS-002. Microbiome changes on affected and non-affected skin.	Skin swabs to evaluate microbiome changes on affected skin that was administered ENS-002	Up to 43 days
Other	Microbiome changes on non-affected skin Microbiome changes on affected and non-affected skin.	Skin swabs to evaluate microbiome changes on non-affected skin	Up to 43 days
Other	Participant preferences and feedback on feasibility and tolerability of ENS-002 administration.	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).	Up to 43 days
Primary	Safety of ENS-002 total doses	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	Up to 43 days
Primary	Safety of ENS-002 dose frequency	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	Up to 43 days
Primary	Safety of ENS-002 different dose durations	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	Up to 43 days
Primary	Tolerability of ENS-002 total doses	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	Up to 43 days
Primary	Tolerability of ENS-002 different dose frequencies	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	Up to 43 days
Primary	Tolerability of ENS-002 different dose durations	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	Up to 43 days
Primary	Recommended Phase 2 Dose (RP2D)	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).	Up to 43 days
Secondary	Levels of Staphylococcus aureus (S. aureus) colonization on affected skin	Measure levels of Staphylococcus aureus (S. aureus) colonization on affected skin by quantitative polymerase chain reaction (qPCR).	Up to 43 days
Secondary	Levels of Staphylococcus aureus (S. aureus) colonization on non-affected skin	Measure levels of Staphylococcus aureus (S. aureus) colonization on non-affected skin at end of treatment compared to baseline by quantitative polymerase chain reaction (qPCR).	Up to 43 days
Secondary	ENS-002 skin colonization	Measure extent of ENS-002 skin colonization at end of treatment compared to baseline quantitative by polymerase chain reaction (qPCR).	Up to 43 days
Secondary	Peak Pruritus Numerical Rating Scale (PPNRS) pruritus	Determine effects of ENS-002 on pruritus by absolute and mean changes in PPNRS at end of treatment compared to baseline	Up to 43 days
Secondary	Peak Pruritus Numerical Rating Scale (PPNRS) affected skin	Determine effects of ENS-002 on affected skin area by absolute and mean changes in PPNRS at end of treatment compared to baseline	Up to 43 days
Secondary	Peak Pruritus Numerical Rating Scale (PPNRS) severity	Determine effects of ENS-002 on severity by absolute and mean changes in PPNRS at end of treatment compared to baseline	Up to 43 days
Secondary	Severity of Pruritus Scale (SPS) pruritus	Determine effects of ENS-002 on pruritus by absolute and mean changes in SPS at end of treatment compared to baseline	Up to 43 days
Secondary	Severity of Pruritus Scale (SPS) affected skin	Determine effects of ENS-002 on affected skin area by absolute and mean changes in SPS at end of treatment compared to baseline	Up to 43 days
Secondary	Severity of Pruritus Scale (SPS) severity	Determine effects of ENS-002 on severity by absolute and mean changes in SPS at end of treatment compared to baseline	Up to 43 days
Secondary	Eczema Area and Severity Index (EASI) pruritus	Determine effects of ENS-002 on pruritus by absolute change and percent of participants with a = 50%,; = 75%, or = 90% reduction in EASI at end of treatment compared to baseline	Up to 43 days
Secondary	Eczema Area and Severity Index (EASI) affected skin	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	Up to 43 days
Secondary	Eczema Area and Severity Index (EASI) severity	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	Up to 43 days
Secondary	Investigator Global Assessment (IGA) 0 to 1	Determine percent of participants with an Investigator Global Assessment (IGA) of 0 or 1 at end of treatment compared to baseline	Up to 43 days
Secondary	Investigator Global Assessment (IGA) absolute decrease of at least 2 points	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	Up to 43 days
Secondary	Body Surface Area (BSA) absolute change	Absolute change from baseline in percent BSA affected	Up to 43 days
Secondary	Body Surface Area (BSA) mean change	Mean change from baseline in percent BSA affected	Up to 43 days
Secondary	Changes in corticosteroid use by participants	Determine type, potency and frequency of corticosteroid use	Up to 43 days
Secondary	Changes in corticosteroid use for flares	Determine number of participants resorting to corticosteroids for flares.	Up to 43 days
Secondary	ENS-002 Administration Compliance - percentage of planned administrations	Assess compliance of actual ENS-002 administrations as a percentage of planned administrations determined by counting used and unused vials and asking participants	Up to 14 days
Secondary	ENS-002 Administration Compliance recorded in ePRO diary	Assess compliance of actual ENS-002 administrations by directed questions as recorded in an electronic participant reported outcome (ePRO) diary.	Up to 14 days