Clinical trial NCT05131477: Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study
Official title: A Phase IIb, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Dose Ranging Study of a Subcutaneous Anti-OX40L Monoclonal Antibody (KY1005) in Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eczema
Atopic Dermatitis
Keywords: KY1005
Monoclonal Antibody
Atopic Dermatitis
Atopic Eczema
OX40L
Lead sponsor: Kymab Limited
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2021-11-23
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 5-arm study to assess the effect of Anti-OX40L Monoclonal Antibody (KY1005) in adult participants with moderate to severe atopic dermatitis.

The estimated duration is 28 days for screening and then up to approximately day 477 (last dose no later than day 337+140 days safety follow-up) for all patients unless enrolled into the LTE (Long-Term Extension) protocol (NCT05492578) at either Day 169 depending on responder status or no later than Day 365 due to loss of clinical response.


Eligibility criteria: Inclusion Criteria:

* Adults (18 to \< 75 years of age) with AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer at Baseline.
* EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline.
* IGA of 3 or 4 at Baseline.
* AD involvement of 10% or more of body surface area (BSA) at Baseline.
* Baseline worst/maximum pruritus NRS of ≥4.
* Documented history, within 6 months prior to Baseline, of either inadequate response or inadvisability of topical treatments.
* Must have applied a stable dose of topical bland emollient (simple moisturizer, no additives \[e.g., urea\]) at least twice daily for a minimum of 7 consecutive days before Baseline.
* Able to complete patient questionnaires.
* Able and willing to comply with requested study visits/telephone visits and procedures.
* Able and willing to provide written informed consent.
* For patients who decide to join the biopsy sub-study be able and willing to provide skin biopsies.

Exclusion Criteria:

* Treatment within specific time windows before the baseline visit for the management of atopic dermatitis such as topical or systemic corticosteroids, biologic or investigational therapies and/or phototherapy.
* 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.
* Weight \<40 kg or \>150 kg at Baseline.
* Treatment with a live (attenuated) immunization within 12 weeks prior to Baseline.
* Men and women (of reproductive potential) unwilling to use birth control and women who are pregnant or breastfeeding.
* Any malignancies or history of malignancies prior to Baseline (except for non-melanoma skin cancer that has been excised and cured for more than 3 years prior to Baseline; in situ cervical carcinoma that has been excised and cured).
* Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at the screening visit.
* 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.
* In the Investigator's opinion, any clinically significant laboratory results from the clinical chemistry, hematology or urinalysis tests at the Screening Visit.
* Concurrent participation in any other clinical study, including non-interventional studies.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage change in EASI (Eczema Area and Severity Index) from Baseline
timeFrame: Baseline to Day 113
Secondary outcomes:
measure: Incidence of treatment-emergent adverse event
timeFrame: Baseline through Day 477
measure: Serum KY1005 concentration assessed throughout the study
timeFrame: Baseline through Day 477
measure: Percentage change in EASI (Eczema Area and Severity Index) from baseline to Day 169
timeFrame: Baseline to Day 169
measure: Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75)
timeFrame: At Days 113 and 169
measure: Percentage of patients with a response of IGA (Investigator Global Assessment) 0 or 1 and a reduction from baseline ≥ 2 points
timeFrame: At Days 113 and 169
measure: Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) ≥ 4 with a baseline pruritus of ≥ 4 from baseline
timeFrame: Days 113 and 169
measure: Absolute change from Baseline in EASI (Eczema Area and Severity Index)
timeFrame: At Days 15, 29, 57, 85, 113, 141 and 169
measure: Percentage change from Baseline in EASI (Eczema Area and Severity Index)
timeFrame: At Days 15, 29, 57, 85 and 141
measure: Percentage of patients with at least a 50% reduction from Baseline in EASI (EASI 50)
timeFrame: At Days 15, 29, 57, 85, 113, 141 and 169
measure: Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75)
timeFrame: At Days 15, 29, 57, 85, and 141
measure: Percentage of patients with at least a 90% reduction from Baseline in EASI (EASI 90)
timeFrame: At Days 15, 29, 57, 85, 113, 141 and 169
measure: Percentage of patients with a 100% reduction from Baseline in EASI (EASI 100)
timeFrame: At Days 15, 29, 57, 85, 113, 141 and 169
measure: Change in IGA (Investigator Global Assessment) from Baseline
timeFrame: Baseline to day 113 and over time up to Day 365
measure: Percentage of patients with a score of IGA (Investigator Global Assessment) 0 or 1 and a reduction from Baseline of ≥ 2 points
timeFrame: At Days 15, 29, 57, 85, and 141
measure: Absolute and Percentage change in SCORAD (SCORing Atopic Dermatitis) Index from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in affected BSA from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in Patient Oriented Eczema Measure (POEM) from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in Dermatology Life Quality Index (DLQI) from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in Atopic Dermatitis Control Tool (ADCT) from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in Hospital Anxiety and Depression Scale (HADS) from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Absolute and Percentage change in weekly average of pruritus Numerical Rating Scale (NRS) from Baseline
timeFrame: Baseline to Day 169 and over time up to Day 365
measure: Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) ≥ 3 with a baseline pruritus NRS ≥ 3 from baseline
timeFrame: Baseline to Days 113 and 169
measure: Incidence of positive anti-Ky1005 antibody response
timeFrame: Baseline through Day 477
measure: Time to loss of EASI 75
timeFrame: Week 24 to Day 365
measure: Time to loss of IGA 0/1 (Patients with a response of 0 or 1 in IGA)
timeFrame: Week 24 to Day 365
measure: Time to loss of EASI 50
timeFrame: Week 24 to Day 365
Other outcomes:
Locations:
city: Fremont
country: United States
facility: Investigative Site Number: 1018
state: California
city: Sacramento
country: United States
facility: Investigative site #1022
state: California
city: Boca Raton
country: United States
facility: Investigative Site Number: 1006
state: Florida
city: Clearwater
country: United States
facility: Investigative Site Number: 1001
state: Florida
city: Coral Gables
country: United States
facility: Investigative Site Number: 1019
state: Florida
city: Miami
country: United States
facility: Investigative Site Number: 1007
state: Florida
city: Tampa
country: United States
facility: Investigative Site Number: 1013
state: Florida
city: Savannah
country: United States
facility: Investigative Site Number: 1004
state: Georgia
city: Clarksville
country: United States
facility: Investigative Site Number: 1010
state: Indiana
city: Indianapolis
country: United States
facility: Investigative Site Number: 1015
state: Indiana
city: Louisville
country: United States
facility: Investigative Site Number: 1021
state: Kentucky
city: Towson
country: United States
facility: Investigative Site Number: 1011
state: Maryland
city: Beverly
country: United States
facility: Investigative Site Number: 1014
state: Massachusetts
city: Troy
country: United States
facility: Investigative Site Number: 1012
state: Michigan
city: Tulsa
country: United States
facility: Investigative Site Number: 1005
state: Oklahoma
city: Portland
country: United States
facility: Investigative Site Number: 1017
state: Oregon
city: Portland
country: United States
facility: Investigative Site Number: 1009
state: Oregon
city: Anderson
country: United States
facility: Investigative Site Number: 1003
state: South Carolina
city: Murfreesboro
country: United States
facility: Investigative Site Number: 1008
state: Tennessee
city: Mansfield
country: United States
facility: Investigative site #1023
state: Texas
city: Carlton
country: Australia
facility: Investigative Site Number 3002
city: East Melbourne
country: Australia
facility: Investigative Site Number: 3003
city: Parkville
country: Australia
facility: Investigational Site Number: 3001
city: Pleven
country: Bulgaria
facility: Investigative Site Number: 2004
city: Sofia
country: Bulgaria
facility: Investigative Site Number: 2005
city: Sofia
country: Bulgaria
facility: Investigative Site Number: 2006
city: Sofia
country: Bulgaria
facility: Investigative Site Number: 2003
city: Sofia
country: Bulgaria
facility: Investigative Site Number: 2002
city: Stara Zagora
country: Bulgaria
facility: Investigative Site Number: 2001
city: Markham
country: Canada
facility: Investigative Site Number: 1106
state: Ontario
city: Niagara Falls
country: Canada
facility: Investigative site #1108
state: Ontario
city: Ottawa
country: Canada
facility: Investigative Site Number: 1103
state: Ontario
city: Waterloo
country: Canada
facility: Investigative Site Number: 1107
state: Ontario
city: Windsor
country: Canada
facility: Investigative Site Number: 1101
state: Ontario
city: Brno
country: Czechia
facility: Investigative Site Number: 2108
state: Jihomoravský Kraj
city: Nový Jicín
country: Czechia
facility: Investigative Site Number: 2105
state: Moravskoslezský Kraj
city: Praha
country: Czechia
facility: Investigative Site Number: 2102
state: Praha, Hlavní Mesto
city: Praha
country: Czechia
facility: Investigative Site Number: 2103
state: Praha, Hlavní Mesto
city: Kutná Hora
country: Czechia
facility: Investigative Site Number: 2106
city: Ostrava
country: Czechia
facility: Investigative Site Number: 2104
city: Erlangen
country: Germany
facility: Investigative Site Number: 2209
state: Bayern
city: Blankenfelde
country: Germany
facility: Investigative Site Number: 2202
state: Brandenburg
city: Münster
country: Germany
facility: Investigator Site Number: 2201
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Investigative Site Number: 2208
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Investigative Site Number: 2203
city: Hamburg
country: Germany
facility: Investigative Site Number: 2204
city: Kecskemét
country: Hungary
facility: Investigative Site Number: 2307
state: Bács-Kiskun
city: Gyula
country: Hungary
facility: Investigative Site Number: 2305
state: Békés
city: Szeged
country: Hungary
facility: Investigative Site Number: 2301
state: Csongrád
city: Debrecen
country: Hungary
facility: Investigative Site Number: 2303
state: Hajdú-Bihar
city: Szolnok
country: Hungary
facility: Investigative Site Number: 2306
state: Jász-Nagykun-Szolnok
city: Zalaegerszeg
country: Hungary
facility: Investigative Site Number: 2302
state: Zala
city: Budapest
country: Hungary
facility: Investigative Site Number: 2304
city: Obihiro-Shi
country: Japan
facility: Investigative Site Number: 3114
state: Hokkaidô
city: Kagoshima-Shi
country: Japan
facility: Investigative site #3108
state: Kagosima
city: Yokohama-Shi
country: Japan
facility: Investigative site #3113
state: Kanagawa
city: Matsudo
country: Japan
facility: Investigative Site Number: 3103
state: Tiba
city: Adachi-Ku
country: Japan
facility: Investigative Site Number: 3112
state: Tokyo
city: Chuo Ku
country: Japan
facility: Investigative Site Number: 3115
state: Tokyo
city: Edagowa-Ku
country: Japan
facility: Investigative Site Number: 3104
state: Tokyo
city: Koto-Ku
country: Japan
facility: Investigative Site Number: 3111
state: Tokyo
city: Minato-Ku
country: Japan
facility: Investigative Site Number: 3107
state: Tokyo
city: Setagaya-Ku
country: Japan
facility: Investigative site #3105
state: Tokyo
city: Kyoto-Shi
country: Japan
facility: Investigative site #3102
city: Mibu-machi
country: Japan
facility: Investigative Site Number: 3106
city: Sapporo
country: Japan
facility: Investigative site #3101
city: Habikino-Shi
country: Japan
facility: Investigative Site Number: 3109
state: Ôsaka
city: Sakai-Shi
country: Japan
facility: Investigative Site Number: 3110
state: Ôsaka
city: Wrocław
country: Poland
facility: Investigative Site Number: 2414
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Investigative Site Number: 2418
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Investigative Site Number: 2417
state: Dolnoslaskie
city: Łódź
country: Poland
facility: Investigative Site Number: 2416
state: Lodzkie
city: Lódz
country: Poland
facility: Investigative Site Number: 2415
state: Lódzkie
city: Łódź
country: Poland
facility: Investigative Site Number: 2420
state: Lódzkie
city: Kraków
country: Poland
facility: Investigative Site Number: 2408
state: Malopolskie
city: Kraków
country: Poland
facility: Investigative Site Number: 2407
state: Malopolskie
city: Kraków
country: Poland
facility: Investigative Site Number: 2409
state: Malopolskie
city: Warszawa
country: Poland
facility: Investigative Site Number: 2412
state: Mazowieckie
city: Warszawa
country: Poland
facility: Investigative Site Number: 2411
state: Mazowieckie
city: Warszawa
country: Poland
facility: Investigative Site Number: 2413
state: Mazowieckie
city: Rzeszów
country: Poland
facility: Investigative Site Number: 2401
state: Podkarpackie
city: Bialystok
country: Poland
facility: Investigative site #2419
state: Podlaskie
city: Gdańsk
country: Poland
facility: Investigative Site Number: 2402
state: Pomorskie
city: Gdynia
country: Poland
facility: Investigative Site Number: 2404
state: Pomorskie
city: Katowice
country: Poland
facility: Investigative Site Number: 2405
state: Slaskie
city: Szczecin
country: Poland
facility: Investigative Site Number: 2410
state: Zachodniopomorskie
city: Białystok
country: Poland
facility: Investigative site #2419
city: Gdańsk
country: Poland
facility: Investigative Site Number: 2403
city: Krakow
country: Poland
facility: Investigative Site Number: 2406
city: Łódź
country: Poland
facility: Investigative site #2420
city: Manises
country: Spain
facility: Investigative Site Number: 2502
state: Valencia
city: Alicante
country: Spain
facility: Investigative Site Number: 2505
city: Córdoba
country: Spain
facility: Investigative Site Number: 2501
city: Madrid
country: Spain
facility: Investigative Site Number: 2503
city: Pontevedra
country: Spain
facility: Investigative Site Number: 2504
city: Niao Song Qu
country: Taiwan
facility: Investigative Site Number: 3201
city: Taichung
country: Taiwan
facility: Investigative Site Number: 3202
city: Taipei
country: Taiwan
facility: Investigative site # 3206
city: Taipei
country: Taiwan
facility: Investigative site # 3206
city: Taoyuan
country: Taiwan
facility: Investigative Site Number: 3203
city: London
country: United Kingdom
facility: Investigative Site Number: 2603
city: London
country: United Kingdom
facility: Investigative Site Number: 2601
city: Sheffield
country: United Kingdom
facility: Investigative Site Number: 2602
Study officials:
References: