A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 4-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with moderate to severe atopic dermatitis. The estimated duration is 15-35 days for screening and then up to approximately day 378 (last dose on day 280 + 98 days safety follow-up) for all patients. Patients with a response at Week 16 (end of induction therapy) will be re-randomized for the maintenance therapy period.

Official Title
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A Phase 2b, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled 54-Week Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis

Conditions
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Moderate to Severe Atopic Dermatitis

Intervention / Treatment
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* Drug: Rezpegaldesleukin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (18 to 70 years of age) with AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer prior to screening. AD disease severity at screening and randomization: EASI of 16 or higher IGA of 3 or 4 BSA of 10% or more Documented history, within 6 months prior to the screening visit, of either inadequate response or inadvisability of topical treatments. Able to complete patient questionnaires. Able and willing to comply with requested study visits and procedures. Able and willing to provide written informed consent. Exclusion Criteria: Prior use of systemic immune modulating therapies for AD (i.e., JAK inhibitors or biologics) Other skin conditions that would interfere with assessment of AD Treatment with a live (attenuated) immunization within 12 weeks prior to screening. Men and women (of reproductive potential) unwilling to use birth control and women who are pregnant or breastfeeding. Any malignancies or history of malignancies within 5 years prior to randomization (except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to randomization). Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at screening. Severe concomitant illness that would in the Investigator's opinion inhibit the patient's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease. Concurrent participation in any other investigational clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Patients will be randomized initially to 1 of 4 groups (A dose regimen, B dose regimen, C dose regimen, or D dose regimen [placebo]) for the blinded induction period. At Week 16, the start of the blinded maintenance period, patients who responded well to treatment will be re-randomized within their previously assigned groups to either maintenance regimen 1 or maintenance regimen 2. At Week 16, patients without an adequate response during the blinded induction period may be assigned to receive open label escape therapy through the maintenance period of the study (up to Week 40); however, patients receiving escape therapy with inadequate improvement in disease severity will be discontinued from the study therapy at week 32. Any patients enrolled into the blinded maintenance period with acute exacerbation of atopic dermatitis may be eligible to receive open label escape therapy instead.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Rezpegaldesleukin Dose Regimen A every 2 weeks during the induction period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|
| Experimental: Arm A1<br>Rezpegaldesleukin Dose Regimen A every 4 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|
| Experimental: Arm A2<br>Rezpegaldesleukin Dose Regimen A every 12 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Experimental: Arm B<br>Rezpegaldesleukin Dose Regimen B every 4 weeks during the induction period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Experimental: Arm B1<br>Rezpegaldesleukin Dose Regimen B every 4 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|
| Experimental: Arm B2<br>Rezpegaldesleukin Dose Regimen B every 12 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Experimental: Arm C<br>Rezpegaldesleukin Dose Regimen C every 2 weeks during the induction period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|
| Experimental: Arm C1<br>Rezpegaldesleukin Dose Regimen C every 4 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|
| Experimental: Arm C2<br>Rezpegaldesleukin Dose Regimen C every 12 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Placebo Comparator: Arm D<br>Placebo every 2 weeks during the induction period | Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Placebo Comparator: Arm D1<br>Placebo every 4 weeks during the maintenance period | Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>|
| Experimental: Escape Therapy (open-label)<br>Rezpegaldesleukin Dose Regimen A every 2 weeks during the maintenance period | Drug: Rezpegaldesleukin<br>* Pharmaceutical form: Injection solution Route of administration: subcutaneous<br>* Other names: LY3471851 (formerly);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change in the Eczema Area and Severity Index (EASI) from baseline at Week 16 | The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis. | Week 0 and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients at week 16 achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 and at least a 2-point reduction from their baseline value | The vIGA-AD scale ranges from 0 to 4, with higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 75% relative to their baseline score (EASI-75) | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 90% relative to their baseline score (EASI-90) | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 50% relative to their baseline score (EASI-50) | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a 4-point or greater improvement in Itch numerical rating scale (NRS) in the subset of patients with a 4-point or greater Itch NRS at baseline | The itch NRS goes from 0 to 10, with higher score indicating more severe itch. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a SCORing Atopic Dermatitis Index (SCORAD) reduction of 75% from their baseline value | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Proportion of patients at week 16 achieving a SCORAD reduction of 50% from their baseline value | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. | Week 0 and Week 16 | 
| Mean change from baseline over the period between week 0 and week 54 in Eczema Area and Severity Index (EASI) | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. | From Week 0 through Week 54 | 
| Mean percent change from baseline over the period between week 0 and week 54 in Eczema Area and Severity Index (EASI) | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. | From Week 0 through Week 54 | 
| Mean change from baseline over the period between week 0 and week 54 in SCORAD | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. | From Week 0 through Week 54 | 
| Mean percent change from baseline over the period between week 0 and week 54 in SCORAD | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. | From Week 0 through Week 54 | 
| Mean change from baseline over the period between week 0 and week 54 in body surface area (BSA) involvement |  | From Week 0 through Week 54 | 
| Mean percent change from baseline over the period between week 0 and week 54 in body surface area (BSA) involvement |  | From Week 0 through Week 54 | 
| Rezpegaldesleukin plasma concentration assessed throughout the study |  | Through end of study (week 54) | 
| Incidence of Serious Adverse Events (SAEs) |  | Through end of study (week 54) | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) |  | Through end of study (week 54) |