Moderate to Severe Atopic Dermatitis
Conditions
Brief summary
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, an Induction Period of 16 weeks, a Maintenance Period from Week 16-Week 52, and a Posttreatment Follow-Up Period for an additional year up to approximately Week 104 for all patients. Patients with a response at Week 16 (end of induction therapy) will be re-randomized for the maintenance therapy period.
Interventions
Pharmaceutical form: Injection solution Route of administration: subcutaneous
DRUGPlacebo
Pharmaceutical form: Injection solution Route of administration: subcutaneous
Sponsors
Nektar Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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 52); 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (from at least 18 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 highly effective 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 successfully treated with no evidence of metastatic disease for 3 years or cervical carcinoma in situ that has been successfully treated, with no evidence of recurrence within the 3 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 virus (HBV) or hepatitis C virus (HCV) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean percent change in the Eczema Area and Severity Index (EASI) from baseline at Week 16 | Week 0 and Week 16 | The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 0 and Week 16 | The vIGA-AD scale ranges from 0 to 4, with higher score indicating more severe atopic dermatitis. |
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 75% relative to their baseline score (EASI-75) | Week 0 and Week 16 | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. |
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 90% relative to their baseline score (EASI-90) | Week 0 and Week 16 | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. |
| Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 50% relative to their baseline score (EASI-50) | Week 0 and Week 16 | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. |
| 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 | Week 0 and Week 16 | The itch NRS goes from 0 to 10, with higher score indicating more severe itch. |
| Proportion of patients at week 16 achieving a SCORing Atopic Dermatitis Index (SCORAD) reduction of 75% from their baseline value | Week 0 and Week 16 | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. |
| Proportion of patients at week 16 achieving a SCORAD reduction of 50% from their baseline value | Week 0 and Week 16 | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. |
| Mean change from baseline over the period between week 0 and week 104 in Eczema Area and Severity Index (EASI) | From Week 0 through Week 104 | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. |
| Mean percent change from baseline over the period between week 0 and week 104 in Eczema Area and Severity Index (EASI) | From Week 0 through Week 104 | The EASI scores range from 0 to 72, with higher score indicating more severe atopic dermatitis. |
| Mean change from baseline over the period between week 0 and week 104 in SCORAD | From Week 0 through Week 104 | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. |
| Mean percent change from baseline over the period between week 0 and week 104 in SCORAD | From Week 0 through Week 104 | The SCORAD scores range from 0 to 103, with a higher score indicating more severe atopic dermatitis. |
| Mean change from baseline over the period between week 0 and week 104 in body surface area (BSA) involvement | From Week 0 through Week 104 | — |
| Mean percent change from baseline over the period between week 0 and week 104 in body surface area (BSA) involvement | From Week 0 through Week 104 | — |
| Rezpegaldesleukin plasma concentration assessed throughout the study | Through end of study (week 104) | — |
| Incidence of Serious Adverse Events (SAEs) | Through end of study (week 104) | — |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Through end of study (week 104) | — |
Countries
Australia, Bulgaria, Canada, Croatia, Czechia, Germany, Hungary, Poland, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
Nektar Therapeutics
Outcome results
None listed