A Phase II Study of Bermekimab (MABp1) in Patients With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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A Phase 2 study of Bermekimab (MABp1) in patients with atopic dermatitis.

Detailed Description
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A Phase 2, Open Label, Dose Escalation Study of Bermekimab (MABp1) in Patients with Moderate to Severe Atopic Dermatitis. The study is multi center and will consist of two dose levels: Group A (n=9): patients will receive a total of 4 x 200mg subcutaneous injections of bermekimab. Dosing will occur weekly from visit 1 to visit 4, inclusive. Group B (n=20): patients will receive a total of 8 x 400 mg subcutaneous injections of bermedimkb. Dosing will occur weekly from visit 1 to visit 8, inclusive.

Official Title
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A Phase II, Open Label, Dose Escalation Study of Bermekimab (MABp1) in Patients With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Bermekimab Monoclonal Antibody 200 mg
* Drug: Bermekimab Monoclonal Antibody 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided by the patient Age 18 years or greater Chronic Atopic Dermatitis present for at least 3 years Disease is not responsive to topical medications, or for whom topical treatments are not indicated or desired. Willing and able to comply with all clinic visits and study-related procedures EASI score ≥16 at screening and baseline visits IGA score ≥3 at screening and baseline visits ≥10% body surface area (BSA) of AD involvement at screening and baseline visits Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable or undesired. Exclusion Criteria: Treatment with an investigational drug within 8 weeks of baseline visit Having received the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment: Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) Phototherapy for AD Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit Initiation of treatment during the screening period with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit) Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit. History of severe allergic or anaphylactic reactions to monoclonal antibodies. Administration of any live (attenuated) vaccine within 4 weeks prior to the baseline. Any history of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma or localized carcinoma in situ of the cervix Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: patients may be rescreened after infection resolves Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit Presence of skin comorbidities that may interfere with study assessments Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study. Examples include, but are not limited to, patients with short life expectancy, patients with uncontrolled diabetes (HbA1c ≥ 9%), patients with cardiovascular conditions (eg, stage III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, patients on dialysis), hepato-biliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe endocrinological, gastrointestinal, metabolic, pulmonary or lymphatic diseases. The specific justification for patients excluded under this criterion will be noted in study documents (chart notes, case report forms [CRFs], etc.) Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study Where relevant, women unwilling to use adequate birth control

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: 200 mg cohort<br>The dose of bermekimab for Group A is 200 mg (2ml of the 100 mg/ml formulation) | Drug: Bermekimab Monoclonal Antibody 200 mg<br>* 200 mg subcutaneous injection<br>|
| Experimental: Group B: 400 mg cohort<br>The dose of bermekimab for Group B is 400 mg (2ml of the 200 mg/ml formulation) administered weekly by subcutaneous injection | Drug: Bermekimab Monoclonal Antibody 400 mg<br>* 400 mg subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Safety and tolerability endpoints were evaluated by monitoring all the adverse events from clinical and laboratory reporting, vital signs, physical examinations, ECG and urinalysis. All the Adverse Events that the subjects experienced from Visit 1 Day 1 (Post-injection) until 7 days after the last administration of the study drug were captured in the clinical database. AEs are coded using medical dictionary - MedDRA Version 21.0 and the severity was assigned using CTCAE version 4.03. | From Visit 1 (Post-injection) until 7 days after the last administration of the study drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Eczema Area and Severity Index (EASI) Score, From Baseline to Week 7 (or Last Visit) | EASI score will assess severity and extent of AD with respect to erythema, excoriation, infiltration and lichenification at 4 anatomic sites of the body: lower and upper extremities, trunk and head. The total EASI score shall be in a range of 0 to 72 points (from no disease to maximum disease severity, respectively). Group A: Change= (Baseline - Week 4 score); Group B: Change= (Baseline - Week 7 score) | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Pharmacokinetics (PK) Assessment at Week 7 | An enzyme-linked immunosorbent assay (ELISA) has been developed to specifically measure bermekimab levels in human plasma. Blood will be drawn into a single 6 ml Na-Heparin collection tube at each PK collection time point. These samples will be collected per the study lab manual and immediately shipped to the Sponsor for PK analysis. The PK samples will also be used to test for the presence of antibodies against bermekimab. PK sample collection time points are as follows: Group A: Pre-dose at visits 1-5; visit 5 is reported Group B: Pre-dose at visit 1, visit 3, visit 5 and visit 8; visit 8 is reported | Group A: Week 4; Group B: Week 7 | 
| Number of Patients Achieving Investigator's Global Assessment (IGA) Response (0 or 1) at Week 7 | IGA assesses disease severity and clinical response using a 5-point scale: 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, 4 = severe. The score is determined by ranking the extent of erythema and population/infiltration. A clinical response to therapy will be an IGA score of 0 (clear) or 1 (almost clear). Patients receiving more than one treatment with additional medication for AD exacerbation during the study or who are missing IGA scores at visit 8 (week 7) will be treated as non-responders. For the 200 mg group, IGA was recorded at visits 1,3, and 5; visit 5 is reported. For the 400 mg group, IGA was recorded at visits 1-8, visit 8 was reported. | Group A: Week 4; Group B: Week 7 | 
| Number of Patients Achieving ≥2 IGA Score Reduction at Week 7 | IGA assesses disease severity and clinical response using a 5-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. The score is determined by ranking the extent of erythema and papulation/infiltration. A clinical response to therapy will be an IGA score of 0 (clear) or 1 (almost clear). | Group A: Week 4; Group B: Week 7 | 
| Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (Overall Itch) From Baseline to Week 7 | The NRS rating system captures the intensity of patient's itch, both maximum and average intensity over a 24-hour period. The following question was presented to patients: How would you rate your itch at the worst moment and on average during the previous 24 hours a scale of 0-10 (0=no itch and 10=worst possible itch)? | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (Worst Moment Itch) From Baseline to Week 7 | The NRS rating system captures the intensity of patient's itch, both maximum and average intensity over a 24-hour period. The following question was presented to patients: How would you rate your itch at the worst moment and on average during the previous 24 hours a scale of 0-10 (0=no itch and 10=worst possible itch)? | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in SCORing Atopic Dermatitis (SCORAD) Score From Baseline to Week 7 | SCORAD was developed by the European Task Force on Atopic Dermatitis. (Severity scoring of Atopic Dermatitis: the SCORAD index), as a measure of disease severity in AD. It includes assessment of the eczema in addition to patient-reported symptoms. Total score ranges from 0 to 103 (no disease to most severe disease, respectively). | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Number of Patients Achieving 50% or Greater Reduction in EASI Score at Week 7 | EASI score will assess severity and extent of AD with respect to erythema, excoriation, infiltration and lichenification at 4 anatomic sites of the body: lower and upper extremities, trunk and head. The total EASI score shall be in a range of 0 to 72 points (from no disease to maximum disease severity, respectively). | Group A: Week 4; Group B: Week 7 | 
| Number of Patients Achieving 50% or Greater Reduction in SCORAD Score at Week 7 | Calculated as per description in Outcome 8. | Group A: Week 4; Group B: Week 7 | 
| Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 7. | POEM is a 7-item patient-reported quality of life outcome measure based on a questionnaire to determine disease symptoms, including bleeding, cracking, dryness, flaking, itching, sleep loss and weeping. The scoring range is from 0 to 28 (no disease to most severe disease, respectively). | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in Global Individual Signs Score (GISS) From Baseline to Week 7 | GISS assesses AD lesions for erythema, excoriations, lichenification and edema/papulation. Each component will be rated on a global basis (over the entire body surface rather than region) using a 4-point scale (0=none, 1=mild, 2=moderate and 3=severe) according to the EASI grading severity. Total score will range from 0 to 12 (no disease to most severe disease, respectively). | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in Dermatology Life Quality Index (DLQI) From Baseline to Week 7 | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on QOL. The format is a simple response (0 to 3 where 0 is not at all and 3 is very much) to 10 questions, which assess QOL over the past week, with an overall scoring system of 0 to 30; a high score is indicative of a poor QOL. | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in HADS (Anxiety) Score From Baseline to Week 7 | The HADS is a set of fourteen questions to be rated by a patient on a four point (0-3) response category so the possible scores range from 0 to 21 for anxiety and 0 to 21 for depression. Scoring is as follows: (0-7)= Normal (8-10)= Borderline Abnormal (11-21)= Abnormal | Group A: Baseline to Week 4; Group B: Baseline to Week 7 | 
| Change in HADS (Depression) Score From Baseline to Week 7 | The HADS is a set of fourteen questions to be rated by a patient on a four point (0-3) response category so the possible scores range from 0 to 21 for anxiety and 0 to 21 for depression. Scoring is as follows: (0-7)= Normal (8-10)= Borderline Abnormal (11-21)= Abnormal | Group A: Baseline to Week 4; Group B: Baseline to Week 7 |