A Study to Assess the Efficacy and Safety of CBP-201 in Adult Subjects With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of CBP-201 in adult subjects with moderate to severe atopic dermatitis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, dose regimen finding study to assess the efficacy, safety, and steady-state PK profile of CBP-201 administered to eligible adult subjects with moderate to severe atopic dermatitis compared to placebo. CBP-201 is administered as a subcutaneous (SC) injection. The study is divided into a treatment period of 16 weeks and a follow-up period of 8 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Multi-Centered Study of the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Moderate-to-severe Atopic Dermatitis

Intervention / Treatment
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* Drug: CBP-201
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be an adult ≥18 and ≤ 75 years of age at the screening visit (Screening) with atopic dermatitis according to American Academy of Dermatology Consensus Criteria, (Eichenfield 2014) Present for at least 1 year prior to the baseline visit (Baseline) with an inadequate response, in the judgement of the Investigator, to AD treatment with a topical regimen of corticosteroids, phosphodiesterase inhibitors or calcineurin inhibitors, or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effect or safety risks) Investigator Global Assessment (IGA) score ≥ 3 at Screening and Baseline. Eczema Area and Severity Index (EASI) score ≥ 16 at Screening and Baseline Body Surface Area (BSA) for total AD involvement ≥ 10% at Screening and Baseline Able and willing to apply a stable dose of a bland emollient twice a day to affected areas for at least 7 days before Baseline and to continue for the duration of the study Females of child-bearing potential (FCBP) and males who have not undergone a vasectomy must abstain from heterosexual activities or agree to use effective contraception throughout the entire study period. Exclusion Criteria: Have any of the following laboratory abnormalities at Screening: Hemoglobin ≤ 90% of the lower limit of normal range (LLN) White blood cell (WBC) below the LLN Neutrophil count below the LLN Platelet count below the LLN Have undergone treatment with any of the following: Topical agents such as corticosteroids, phosphodiesterase (PDE) inhibitors, Janus kinase (JAK) inhibitors, tacrolimus or pimecrolimus within 1 week prior to Baseline. Note that low to medium potency topical corticosteroids (TCS) are permitted after randomization to treat AD flares Prior treatment with dupilumab or any antibody against IL-4Rα or IL-13 Systemic treatment for AD or other condition with steroids or other immunosuppressive/immunomodulating substances, e.g., cyclosporine, mycophenolate-mofetil, azathioprine, methotrexate or oral Janus kinase (JAK) inhibitors within 4 weeks prior to Baseline. Use of steroid inhalers and nasal corticosteroids is allowed. Cell depleting agents, e.g. rituximab, within 6 months of Baseline or treatment with other biologics within 5 half-lives (if known) or 3 months prior to baseline visit, whichever is longer Phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), tanning beds, or any other light emitting device (LED), within 4 weeks of Baseline ≥ 2 bleach baths within 2 weeks of Baseline Prescription emollient to treat AD (e.g. Atopiclair®, MimyX®, Epicerum®, etc.) within 2 weeks of Baseline Any investigational drug within 30 days or within 5 half-lives, whichever is longer, before Baseline. Live (attenuated) vaccine within 8 weeks of Baseline. Treatment with systemic traditional Chinese medicine (TCM) or herbal medications within 4 weeks before Baseline or treatment with topical TCM or herbal medications within 1 week before Baseline visit Have any of the following: Infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks before Baseline, or superficial skin infection, such as impetigo, within 2 weeks before the Baseline (subjects may be rescreened after the infection has resolved) A history of parasitic infection (e.g. helminth), within 6 months of Baseline Per investigator judgement, known or suspected history of immunosuppression within 6 months of Baseline, including a history of invasive opportunistic infections, such as aspergillosis, coccidioidomycosis, histoplasmosis, human immunodeficiency virus (HIV), listeriosis, pneumocystosis, or tuberculosis, despite infection resolution; or unusually frequent, recurrent or prolonged infections. Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) A history of malignancy with the following exceptions: completely treated carcinoma in situ of cervix or non-metastatic squamous or basal cell carcinoma of the skin Positive results at Screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody with positive HCV RNA polymerase chain reaction; positive HIV serology at screening An allergy to L-histidine, trehalose or Tween (polysorbate) 80 Women must not be pregnant, planning to become pregnant or breast-feed during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBP-201 Dose 1<br>CBP-201 Dose 1 subcutaneous (SC) injection | Drug: CBP-201<br>* CBP-201 subcutaneous(SC) injection.<br>|
| Experimental: CBP-201 Dose 2<br>CBP-201 Dose 2 subcutaneous (SC) injection | Drug: CBP-201<br>* CBP-201 subcutaneous(SC) injection.<br>|
| Experimental: CBP-201 Dose 3<br>CBP-201 Dose 3 subcutaneous (SC) injection | Drug: CBP-201<br>* CBP-201 subcutaneous(SC) injection.<br>|
| Placebo Comparator: placebo<br>subcutaneous (SC) injection | Drug: placebo<br>* subcutaneous(SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction in EASI Score From Baseline to Week 16 | EASI=Eczema Area Severity Index is a validated physician score for signs of atopic dermatitis. EASI can range from 0 to 72. An EASI score of 0 indicates clear/no eczema, 0.1 to 1.0 almost clear, 1.1 to 7 mild disease, 7.1 to 21 moderate disease, 21.1 to 50 severe disease, and 51-72 indicates very severe disease. EASI Sub-scale ranges are as follows: Head/neck can range from 0-7.2, Trunk 0-14.4, Upper Extremities 0-21.6, Lower Extremities can range from 0-28.8. To calculate EASI, % involvement is first assessed by body region with an Area involvement Score of 0-6 for each region: 0=0%, 1=1-9%, 2=10-29%, 3=30-39%, 4=50-69%, 5=70-89%, 6=90-100% involvement. Then 4 attributes (Erythema, Edema/Papulation, Excoriation, and Lichenification) are scored for severity (0= none, 1=mild, 2=moderate, 3=severe). A multiplier is applied head/neck=0.1, trunk=0.2, upper extremities= 0.3, lower extremities=0.4. The total EASI score is the sum of 4 regional sub-scores. | Reduction from baseline to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vIGA of 0/1 at Week 16 | Validated Investigator Global Assessment Score (vIGA) is assigned by the physician based on morphologic presentation of the disease in the clinic. The physician considers extent and severity of erythema, induration/papulation, lichenification, and oozing/crusting. A vIGA Score of 0=Clear, 1=Almost Clear, 2= Mild dermatitis, 3=Moderate dermatitis, and 4= Severe dermatitis. Patients are required to have a baseline IGA of 3 or 4. The response rate or percentage of patients achieving a vIGA of 0 or 1 (improved to clear or almost clear) at week 16 is the outcome. | Response Rate at 16 weeks |