NCT06469385终止1 期
Phase 1 First in Human Dose Escalation and Safety Study of Topical ENS-002 for Atopic Dermatitis in Adults
Concerto Biosciences3 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2024年9月18日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and sign an informed consent form (ICF).
- •Age 18 years or older on the day of signing the ICF.
- •Diagnosis of AD according to Hanifin and Rajka
- •Atopic dermatitis has been diagnosed and present for ≥ 6 months prior to the first planned ENS-002 administration.
- •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.
- •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.
- •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.
- •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.
- •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.
- •Urinalysis.
- •12-lead electrocardiogram.
- •For women of childbearing potential (WOCBP), serum and/or urine test consistent with a non-pregnant state.
- •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.
- •Willing and able to complete once-daily electronic diary entries for the duration of the study.
排除标准
- •Has only facial AD.
- •Has more than 20 Geographic Body Site Areas (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. These GBSA restrictions exclude face, scalp, genitalia, and groin lesions. If the total number of allowable GBSAs is exceeded, the participant may be allowed to enroll after discussion with the Concerto Medical Monitor, but these additional sites must not have ENS-002 applied.
- •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).
- •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.
- •Presence of indwelling arterial or venous catheters.
- •Cardiac valve disease history or artificial valve or pacemaker in place.
- •Implanted devices/prostheses including, but not limited to, eye lens, knee, hip, dental implants (but not caps or crowns), etc. replacements.
- •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]).
- •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.
- •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.
- •Clinically significant immunodeficiency (congenital or acquired [including a history of treated or untreated HIV, malnutrition, chronic viral infection]).
- •Netherton syndrome or other genodermatoses resulting in a defective epidermal barrier.
- •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).
- •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.
- •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 low- to mid-potency creams (and lotions, gels, foams, etc.); use of allowed topical corticosteroids only after discussion and agreement with Medical Monitor, 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-interluekin-6 (anti-IL-6) antibody, anti-IL-1 antibody, or anti-CD20 antibody).
- •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.
- •Received oral or systemic antibiotics within 21 days prior to screening.
- •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.
- •Exceptions:
- •allowed emollients and low- and mid-potency corticosteroid creams. Low- and mid-potency corticosteroid creams may be allowed without a washout, but only after discussion and agreement with Concerto Medical Monitor. Allowed emollients may be substituted for disallowed emollients during screening as long as this occurs at least 7 days before the planned first ENS-002 administration.
- •Therapy prior to the first planned dose of ENS-002 with one or more of the following:
- •Systemic corticosteroids within 28 days
- •Topical high-potency corticosteroids within 28 days
- •Low- and mid-potency corticosteroid creams within 14 days. These may be allowed if the participant is on a stable dose and after discussion and agreement with the Concerto Medical Monitor.
- •Topical phosphodiesterase inhibitors within 7 days
- •Emollients within 7 days, other than those emollients allowed in this study. 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-
- •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-
- •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.
- •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).
- •Concurrent therapy with dupilumab, tralokinumab, or lebrikizumab is allowed as long as participant has been on a stable dose for
- •≥ 16 weeks prior to the first planned dose of ENS-
- •If a participant was taking any of these agents but has stopped, then a 56-day or five half-lives (whichever is longer) period is required before the first planned dose of ENS-
- •Bleach baths within 30 days prior to the first planned dose of ENS-
- •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-
- •Allergic to any of the excipients in ENS-002 (pea hydrolysate, potassium phosphate dibasic, sodium chloride, yeast extract, water for injection, glycerol, and methylcellulose).
- •Unable to use at least 2 of the 6 rescue antibiotics that cover all 3 bacteria in ENS-
- •Pregnant or planning to attempt to become pregnant during this study, breast feeding, breast pumping, or planning to breast feed.
- •Participant with a pregnant or breastfeeding partner or a partner planning to attempt to become pregnant during the study.
- •Unable to demonstrate proper ENS-002 application technique despite proficiency training.
- •Any prior exposure to ENS-
- •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 during this study and for 90 days after the last administration of ENS-
- •If biologically male and fertile, cannot donate sperm and must adhere to highly effective birth control measures during this study and for 90 days after the last administration of ENS-002.
研究组 & 干预措施
ENS-002
Experimental
ENS-002 lotion to be applied topically either once or twice per day depending on assigned study cohort.
Cohort 1 - once daily dose (QD) of low dose ENS-002. This dose will be applied topically to a single target site once daily for 7 days.
Cohort 2 - QD dose of high dose ENS-002 in subjects with mild, moderate or severe Atopic Dermatitis. This dose will be applied topically to all affected skin (excluding scalp, face, groin, genitalia) once daily for 14 days.
Cohort 3 - twice daily (BID) dose of high dose ENS-002 in subjects with mild, moderate or severe Atopic Dermatitis applied topically to all affected skin (excluding scalp, face, groin, genitalia) twice daily for 14 days
干预措施: ENS-002 (Biological)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: 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).
Tolerability of ENS-002 different dose durations
时间窗: 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
Safety of ENS-002 dose frequency
时间窗: 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
时间窗: 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
Safety of ENS-002 total doses
时间窗: 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
Tolerability of ENS-002 total doses
时间窗: 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
时间窗: 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
次要结局
- Levels of specified bacterial colonization on affected skin(Up to 43 days)
- Severity of Pruritus Scale (SPS) pruritus(Up to 43 days)
- Severity of Pruritus Scale (SPS) affected skin(Up to 43 days)
- Severity of Pruritus Scale (SPS) severity(Up to 43 days)
- Investigator Global Assessment (IGA) 0 to 1(Up to 43 days)
- Body Surface Area (BSA) absolute change(Up to 43 days)
- ENS-002 Administration Compliance - percentage of planned administrations(Up to 14 days)
- Eczema Area and Severity Index (EASI) affected skin(Up to 43 days)
- Investigator Global Assessment (IGA) absolute decrease of at least 2 points(Up to 43 days)
- Body Surface Area (BSA) mean change(Up to 43 days)
- ENS-002 Administration Compliance recorded in ePRO diary(Up to 14 days)
- Peak Pruritus Numerical Rating Scale (PPNRS) affected skin(Up to 43 days)
- Changes in corticosteroid use by participants(Up to 43 days)
- Changes in corticosteroid use for flares(Up to 43 days)
- Levels of specified bacterial colonization on non-affected skin(Up to 43 days)
- Peak Pruritus Numerical Rating Scale (PPNRS) pruritus(Up to 43 days)
- Eczema Area and Severity Index (EASI) severity(Up to 43 days)
- ENS-002 skin colonization(Up to 43 days)
- Peak Pruritus Numerical Rating Scale (PPNRS) severity(Up to 43 days)
研究者
研究点 (3)
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