Clinical trial NCT06136741: A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis
Official title: A Phase 2b, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis (REZOLVE-AD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Moderate to Severe Atopic Dermatitis
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean percent change in the Eczema Area and Severity Index (EASI) from baseline at Week 16
timeFrame: Week 0 and Week 16
Secondary outcomes:
measure: 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
timeFrame: Week 0 and Week 16
measure: Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 75% relative to their baseline score (EASI-75)
timeFrame: Week 0 and Week 16
measure: Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 90% relative to their baseline score (EASI-90)
timeFrame: Week 0 and Week 16
measure: Proportion of patients at week 16 achieving a Eczema Area and Severity Index reduction of 50% relative to their baseline score (EASI-50)
timeFrame: Week 0 and Week 16
measure: 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
timeFrame: Week 0 and Week 16
measure: Proportion of patients at week 16 achieving a SCORing Atopic Dermatitis Index (SCORAD) reduction of 75% from their baseline value
timeFrame: Week 0 and Week 16
measure: Proportion of patients at week 16 achieving a SCORAD reduction of 50% from their baseline value
timeFrame: Week 0 and Week 16
measure: Mean change from baseline over the period between week 0 and week 104 in Eczema Area and Severity Index (EASI)
timeFrame: From Week 0 through Week 104
measure: Mean percent change from baseline over the period between week 0 and week 104 in Eczema Area and Severity Index (EASI)
timeFrame: From Week 0 through Week 104
measure: Mean change from baseline over the period between week 0 and week 104 in SCORAD
timeFrame: From Week 0 through Week 104
measure: Mean percent change from baseline over the period between week 0 and week 104 in SCORAD
timeFrame: From Week 0 through Week 104
measure: Mean change from baseline over the period between week 0 and week 104 in body surface area (BSA) involvement
timeFrame: From Week 0 through Week 104
measure: Mean percent change from baseline over the period between week 0 and week 104 in body surface area (BSA) involvement
timeFrame: From Week 0 through Week 104
measure: Rezpegaldesleukin plasma concentration assessed throughout the study
timeFrame: Through end of study (week 104)
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Through end of study (week 104)
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Through end of study (week 104)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Nektar Investigative Site
state: Arizona
city: Bryant
country: United States
facility: Nektar Investigative Site
state: Arkansas
city: Fountain Valley
country: United States
facility: Nektar Investigative Site
state: California
city: Los Angeles
country: United States
facility: Nektar Investigative Site
state: California
city: Los Angeles
country: United States
facility: Nektar Investigative Site
state: California
city: Los Angeles
country: United States
facility: Nektar Investigative Site
state: California
city: Santa Monica
country: United States
facility: Nektar Investigative Site
state: California
city: Hialeah
country: United States
facility: Nektar Investigative Site
state: Florida
city: Hollywood
country: United States
facility: Nektar Investigative Site
state: Florida
city: Miami Lakes
country: United States
facility: Nektar Investigative Site
state: Florida
city: Miami
country: United States
facility: Nektar Investigative Site
state: Florida
city: Saint Petersburg
country: United States
facility: Nektar Investigative Site
state: Florida
city: Tampa
country: United States
facility: Nektar Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Nektar Investigative Site
state: Georgia
city: Marietta
country: United States
facility: Nektar Investigative Site
state: Georgia
city: Clarksville
country: United States
facility: Nektar Investigative Site
state: Indiana
city: Indianapolis
country: United States
facility: Nektar Investigative Site
state: Indiana
city: Louisville
country: United States
facility: Nektar Investigative Site
state: Kentucky
city: New Orleans
country: United States
facility: Nektar Investigative Site
state: Louisiana
city: Bay City
country: United States
facility: Nektar Investigative Site
state: Michigan
city: Flint
country: United States
facility: Nektar Investigative Site
state: Michigan
city: Troy
country: United States
facility: Nektar Investigative Site
state: Michigan
city: Las Vegas
country: United States
facility: Nektar Investigative Site
state: Nevada
city: Las Vegas
country: United States
facility: Nektar Investigative Site
state: Nevada
city: New York
country: United States
facility: Nektar Investigative Site
state: New York
city: Fairborn
country: United States
facility: Nektar Investigative Site
state: Ohio
city: Mayfield Heights
country: United States
facility: Nektar Investigative Site
state: Ohio
city: Camp Hill
country: United States
facility: Nektar Investigative Site
state: Pennsylvania
city: Murfreesboro
country: United States
facility: Nektar Investigative Site
state: Tennessee
city: Bellaire
country: United States
facility: Nektar Investigative Site
state: Texas
city: Cypress
country: United States
facility: Nektar Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Nektar Investigative Site
state: Texas
city: Frisco
country: United States
facility: Nektar Investigative Site
state: Texas
city: Spokane
country: United States
facility: Nektar Investigative Site
state: Washington
city: Spokane
country: United States
facility: Nektar Investigative Site
state: Washington
city: Darlinghurst
country: Australia
facility: Nektar Investigative Site
state: New South Wales
city: Kogarah
country: Australia
facility: Nektar Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Nektar Investigative Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Nektar Investigative Site
state: Queensland
city: Campbelltown
country: Australia
facility: Nektar Investigative Site
state: South Australia
city: East Melbourne
country: Australia
facility: Nektar Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Nektar Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Nektar Investigative Site
state: Western Australia
city: Sevlievo
country: Bulgaria
facility: Nektar Investigative Site
state: Gabrovo
city: Dupnitsa
country: Bulgaria
facility: Nektar Investigative Site
state: Kjustendil
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
state: Sofia-Grad
city: Lovech
country: Bulgaria
facility: Nektar Investigative Site
city: Pleven
country: Bulgaria
facility: Nektar Investigative Site
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
city: Sofia
country: Bulgaria
facility: Nektar Investigative Site
city: Calgary
country: Canada
facility: Nektar Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Nektar Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Nektar Investigative Site
state: Alberta
city: Kelowna
country: Canada
facility: Nektar Investigative Site
state: British Columbia
city: Surrey
country: Canada
facility: Nektar Investigative Site
state: British Columbia
city: Barrie
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Markham
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Oakville
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Peterborough
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Richmond Hill
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Nektar Investigative Site
state: Ontario
city: Québec
country: Canada
facility: Nektar Investigative Site
state: Quebec
city: Zagreb
country: Croatia
facility: Nektar Investigative Site 5701
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Nektar Investigative Site 5703
state: Grad Zagreb
city: Ivanić-Grad
country: Croatia
facility: Nektar Investigative Site
city: Brno
country: Czechia
facility: Nektar Investigative Site
city: Pardubice
country: Czechia
facility: Nektar Investigative Site
city: Praha 10
country: Czechia
facility: Nektar Investigative Site
city: Praha 5
country: Czechia
facility: Nektar Investigative Site
city: Augsburg
country: Germany
facility: Nektar Investigative Site
state: Bayern
city: Augsburg
country: Germany
facility: Nektar Investigator Site
state: Bayern
city: Erlangen
country: Germany
facility: Nektar Investigative Site
state: Bayern
city: Blankenfelde
country: Germany
facility: Nektar Investigative Site
state: Brandenburg
city: Bad Bentheim
country: Germany
facility: Nektar Investigative Site
state: Niedersachsen
city: Bramsche
country: Germany
facility: Nektar Investigative Site
state: Niedersachsen
city: Dülmen
country: Germany
facility: Nektar Investigative Site
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: Nektar Investigative Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Nektar Investigative Site
state: Rheinland-Pfalz
city: Leipzig
country: Germany
facility: Nektar Investigative Site
state: Sachsen
city: Berlin
country: Germany
facility: Nektar Investigative Site
city: Berlin
country: Germany
facility: Nektar Investigative Site
city: Darmstadt
country: Germany
facility: Nektar Investigative Site
city: Frankfurt
country: Germany
facility: Nektar Investigative Site
city: Hamburg
country: Germany
facility: Nektar Investigative Site
city: Luebeck
country: Germany
facility: Nektar Investigative Site
city: Muenchen
country: Germany
facility: Nektar Investigator Site
city: Gyula
country: Hungary
facility: Nektar Investigative Site
state: Békés
city: Zalaegerszeg
country: Hungary
facility: Nektar Investigative Site
state: Zala
city: Wroclaw
country: Poland
facility: Nektar Investigative Site
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Nektar Investigative Site
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Nektar Investigative Site
state: Dolnoslaskie
city: Warszawa
country: Poland
facility: Nektar Investigative Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Nektar Investigative Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Nektar Investigative Site
state: Mazowieckie
city: Rzeszów
country: Poland
facility: Nektar Investigative Site
state: Podkarpackie
city: Gdańsk
country: Poland
facility: Nektar Investigative Site
state: Pomorskie
city: Gdańsk
country: Poland
facility: Nektar Investigative Site
state: Pomorskie
city: Gdynia
country: Poland
facility: Nektar Investigative Site
state: Pomorskie
city: Częstochowa
country: Poland
facility: Nektar Investigative Site
city: Iława
country: Poland
facility: Nektar Investigative Site
city: Katowice
country: Poland
facility: Nektar Investigative Site
city: Krakow
country: Poland
facility: Nektar Investigative Site
city: Kraków
country: Poland
facility: Nektar Investigator Site
city: Kraków
country: Poland
facility: Nektar Investigative Site
city: Kraków
country: Poland
facility: Nektar Investigative Site
city: Poznań
country: Poland
facility: Nektar Investigative Site
city: Szczecin
country: Poland
facility: Nektar Investigative Site
city: Tarnów
country: Poland
facility: Nektar Investigative Site
city: Warszawa
country: Poland
facility: Nektar Investigative Site
city: Warszawa
country: Poland
facility: Nektar Investigative Site
city: Warszawa
country: Poland
facility: Nektar Investigative Site
city: Wrocław
country: Poland
facility: Nektar Investigative Site
city: Wrocław
country: Poland
facility: Nektar Investigative Site
city: Łódź
country: Poland
facility: Nektar Investigative Site
city: Łódź
country: Poland
facility: Nektar Investigative Site
city: Manises
country: Spain
facility: Nektar Investigative Site
state: Valencia
city: Alicante
country: Spain
facility: Nektar Investigative Site
city: Córdoba
country: Spain
facility: Nektar Investigative Site
city: Granada
country: Spain
facility: Nektar Investigative Site
city: Sevilla
country: Spain
facility: Nektar Investigative Site
city: Zaragoza
country: Spain
facility: Nektar Investigative Site
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References: