A Study to Evaluate of the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Acneiform Rash

Study Overview
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Brief Summary
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Efficacy and Safety of imsidolimab in participants with epidermal growth factor receptor inhibitor (EGFRi)/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor (MEKi)-associated acneiform Rash

Detailed Description
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This study is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of imsidolimab compared with placebo in cancer participants with EGFRi/MEKi-associated acneiform rash. This study will also characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to imsidolimab in participants with EGFRi/MEKi-associated acneiform rash.

Official Title
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A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ANB019 in the Treatment of Acneiform Rash in Subjects With Neoplasm Receiving EGFRi or MEKi Therapy

Conditions
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Acneiform Eruptions

Intervention / Treatment
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* Biological: Imsidolimab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has cancer Participant is treated with an oral or injectable Food and Drug Administration (FDA)-approved EGFRi or MEKi therapy Participant has EGFRi/MEKi-related acneiform rash of Grade ≥ 2 as per common terminology criteria for adverse events (CTCAE) version 5.0, and ≥ 20 inflammatory lesions on the face at screening and Day 1. Exclusion Criteria: Participant has infected EGFRi/MEKi-associated acneiform rash according to investigator's evaluation. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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: ANB019<br>Participants received a starting dose of 400 milligrams (mg) of imsidolimab on Day 1 followed by 200 mg imsidolimab every 4 weeks (Days 29, 57 and 85) by subcutaneous injection. | Biological: Imsidolimab<br>* Humanized monoclonal antibody<br>* Other names: ANB019;|
| Placebo Comparator: Placebo<br>Participants received imsidolimab matching placebo on Day 1 and thereafter, every 4 weeks (Days 29, 57 and 85) by subcutaneous injection. | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8 | The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 millimeters (mm) or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8 | The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 mm or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate. | Baseline, Week 8 | 
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Common Terminology Criteria for Adverse Events (CTCAE) Grading Scale at Week 8 | The acneiform rash CTCAE grading scale of severity was 6-point scale ranging from 0-5. Scale 0=no evidence of rash. Scale 1= papules and/or pustules covering <10% body surface area (BSA), which may or may not be associated with symptoms of pruritus or tenderness. Scale 2=papules and/or pustules covering 10-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychosocial impact; limiting instrumental activities of daily living (ADL); papules and/or pustules covering >30% BSA with or without mild symptoms. Scale 3=papules and/or pustules covering >30% BSA with moderate or severe symptoms; limiting self-care ADL; associated with local superinfection with oral antibiotics. Scale 4=life-threatening consequences; papules and/or pustules covering any %BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with intravenous (IV) antibiotics indicated. Scale 5=death. | Baseline, Week 8 | 
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash CTCAE Grading Scale | Time to first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale: Date of the first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. | Baseline up to 55 days | 
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified Multinational Association for Supportive Care in Cancer (MASCC) EGFRi Skin Toxicity Tool (MESTT) Grading Scale (Total Score) at Week 8 | The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema <1 centimeter (cm) in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema <1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema <1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema <1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules > 20; OR more than 5 areas of erythema or edema <1 cm in size. 3B: papules or pustules > 20; OR more than 5 areas of erythema or edema <1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face, scalp, chest, and back. The sum of all body region scores yielded the total score (range: 4 to 12). | Baseline, Week 8 | 
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Total Score) | Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. | Baseline to 55 days | 
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified MESTT Grading Scale (Facial Assessment) at Week 8 | The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema <1cm in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema <1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema <1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema <1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules > 20; OR more than 5 areas of erythema or edema <1 cm in size. 3B: papules or pustules > 20; OR more than 5 areas of erythema or edema <1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face. The score ranged from 1 to 3. | Baseline, Week 8 | 
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Facial Assessment) | Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. | Baseline to 55 days | 
| Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 8 | The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. | Baseline, Week 8 | 
| Percent Change From Baseline in Pruritus NRS at Week 8 | The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. | Baseline, Week 8 | 
| Change From Baseline in Pain NRS at Week 8 | The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain. | Baseline, Week 8 | 
| Percent Change From Baseline in Pain NRS at Week 8 | The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain. | Baseline, Week 8 | 
| Change From Baseline in Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRi-18) at Week 8 | The FACT-EGFRi-18 was an 18-item likert-scaled questionnaire, arranged in three dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 (not at all) to 4 (very much). The total score was obtained by multiplying the sum of the subscale by the number of items in the scale (18), and then dividing by the number of items actually answered. The total score ranged from 0-72 with a higher score represented a high level of symptomatology (problems). | Baseline, Week 8 | 
| Number of Participants With Treatment-Emergent Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to study treatment. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study treatment that did not necessarily have a causal relationship with this treatment. An AE was considered serious if there was any of the following outcomes: death, life-threatening, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment. | From first dose to 55 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-36 receptor, Interleukin 36, Imsidolimab