Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study

Atopic Dermatitis Clinical Trial

— STREAM-AD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05131477
• Other study ID #: KY1005-CT05/DRI17366
• Secondary ID: 2021-000725-28U1
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2021
• Est. completion date: February 21, 2024

Study information

• Verified date: April 2024
• Source: Kymab Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: February 21, 2024
• Est. primary completion date: April 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• KY1005
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Locations

Country	Name	City	State
Australia	Investigative Site Number 3002	Carlton
Australia	Investigative Site Number: 3003	East Melbourne
Australia	Investigational Site Number: 3001	Parkville
Bulgaria	Investigative Site Number: 2004	Pleven
Bulgaria	Investigative Site Number: 2002	Sofia
Bulgaria	Investigative Site Number: 2003	Sofia
Bulgaria	Investigative Site Number: 2005	Sofia
Bulgaria	Investigative Site Number: 2006	Sofia
Bulgaria	Investigative Site Number: 2001	Stara Zagora
Canada	Investigative Site Number: 1106	Markham	Ontario
Canada	Investigative site #1108	Niagara Falls	Ontario
Canada	Investigative Site Number: 1103	Ottawa	Ontario
Canada	Investigative Site Number: 1107	Waterloo	Ontario
Canada	Investigative Site Number: 1101	Windsor	Ontario
Czechia	Investigative Site Number: 2108	Brno	Jihomoravský Kraj
Czechia	Investigative Site Number: 2106	Kutná Hora
Czechia	Investigative Site Number: 2105	Nový Jicín	Moravskoslezský Kraj
Czechia	Investigative Site Number: 2104	Ostrava
Czechia	Investigative Site Number: 2102	Praha	Praha, Hlavní Mesto
Czechia	Investigative Site Number: 2103	Praha	Praha, Hlavní Mesto
Germany	Investigative Site Number: 2203	Berlin
Germany	Investigative Site Number: 2202	Blankenfelde	Brandenburg
Germany	Investigative Site Number: 2209	Erlangen	Bayern
Germany	Investigative Site Number: 2204	Hamburg
Germany	Investigative Site Number: 2208	Kiel	Schleswig-Holstein
Germany	Investigator Site Number: 2201	Münster	Nordrhein-Westfalen
Hungary	Investigative Site Number: 2304	Budapest
Hungary	Investigative Site Number: 2303	Debrecen	Hajdú-Bihar
Hungary	Investigative Site Number: 2305	Gyula	Békés
Hungary	Investigative Site Number: 2307	Kecskemét	Bács-Kiskun
Hungary	Investigative Site Number: 2301	Szeged	Csongrád
Hungary	Investigative Site Number: 2306	Szolnok	Jász-Nagykun-Szolnok
Hungary	Investigative Site Number: 2302	Zalaegerszeg	Zala
Japan	Investigative Site Number: 3112	Adachi-Ku	Tokyo
Japan	Investigative Site Number: 3115	Chuo Ku	Tokyo
Japan	Investigative Site Number: 3104	Edagowa-Ku	Tokyo
Japan	Investigative Site Number: 3109	Habikino-Shi	Ôsaka
Japan	Investigative site #3108	Kagoshima-Shi	Kagosima
Japan	Investigative Site Number: 3111	Koto-Ku	Tokyo
Japan	Investigative site #3102	Kyoto-Shi
Japan	Investigative Site Number: 3103	Matsudo	Tiba
Japan	Investigative Site Number: 3106	Mibu-machi
Japan	Investigative Site Number: 3107	Minato-Ku	Tokyo
Japan	Investigative Site Number: 3114	Obihiro-Shi	Hokkaidô
Japan	Investigative Site Number: 3110	Sakai-Shi	Ôsaka
Japan	Investigative site #3101	Sapporo
Japan	Investigative site #3105	Setagaya-Ku	Tokyo
Japan	Investigative site #3113	Yokohama-Shi	Kanagawa
Poland	Investigative site #2419	Bialystok	Podlaskie
Poland	Investigative site #2419	Bialystok
Poland	Investigative Site Number: 2402	Gdansk	Pomorskie
Poland	Investigative Site Number: 2403	Gdansk
Poland	Investigative Site Number: 2404	Gdynia	Pomorskie
Poland	Investigative Site Number: 2405	Katowice	Slaskie
Poland	Investigative Site Number: 2406	Krakow
Poland	Investigative Site Number: 2407	Kraków	Malopolskie
Poland	Investigative Site Number: 2408	Kraków	Malopolskie
Poland	Investigative Site Number: 2409	Kraków	Malopolskie
Poland	Investigative site #2420	Lódz
Poland	Investigative Site Number: 2415	Lódz	Lódzkie
Poland	Investigative Site Number: 2416	Lódz	Lodzkie
Poland	Investigative Site Number: 2420	Lódz	Lódzkie
Poland	Investigative Site Number: 2401	Rzeszów	Podkarpackie
Poland	Investigative Site Number: 2410	Szczecin	Zachodniopomorskie
Poland	Investigative Site Number: 2411	Warszawa	Mazowieckie
Poland	Investigative Site Number: 2412	Warszawa	Mazowieckie
Poland	Investigative Site Number: 2413	Warszawa	Mazowieckie
Poland	Investigative Site Number: 2414	Wroclaw	Dolnoslaskie
Poland	Investigative Site Number: 2417	Wroclaw	Dolnoslaskie
Poland	Investigative Site Number: 2418	Wroclaw	Dolnoslaskie
Spain	Investigative Site Number: 2505	Alicante
Spain	Investigative Site Number: 2501	Córdoba
Spain	Investigative Site Number: 2503	Madrid
Spain	Investigative Site Number: 2502	Manises	Valencia
Spain	Investigative Site Number: 2504	Pontevedra
Taiwan	Investigative Site Number: 3201	Niao Song Qu
Taiwan	Investigative Site Number: 3202	Taichung
Taiwan	Investigative site # 3206	Taipei
Taiwan	Investigative site # 3206	Taipei
Taiwan	Investigative Site Number: 3203	Taoyuan
United Kingdom	Investigative Site Number: 2601	London
United Kingdom	Investigative Site Number: 2603	London
United Kingdom	Investigative Site Number: 2602	Sheffield
United States	Investigative Site Number: 1003	Anderson	South Carolina
United States	Investigative Site Number: 1014	Beverly	Massachusetts
United States	Investigative Site Number: 1006	Boca Raton	Florida
United States	Investigative Site Number: 1010	Clarksville	Indiana
United States	Investigative Site Number: 1001	Clearwater	Florida
United States	Investigative Site Number: 1019	Coral Gables	Florida
United States	Investigative Site Number: 1018	Fremont	California
United States	Investigative Site Number: 1015	Indianapolis	Indiana
United States	Investigative Site Number: 1021	Louisville	Kentucky
United States	Investigative site #1023	Mansfield	Texas
United States	Investigative Site Number: 1007	Miami	Florida
United States	Investigative Site Number: 1008	Murfreesboro	Tennessee
United States	Investigative Site Number: 1009	Portland	Oregon
United States	Investigative Site Number: 1017	Portland	Oregon
United States	Investigative site #1022	Sacramento	California
United States	Investigative Site Number: 1004	Savannah	Georgia
United States	Investigative Site Number: 1013	Tampa	Florida
United States	Investigative Site Number: 1011	Towson	Maryland
United States	Investigative Site Number: 1012	Troy	Michigan
United States	Investigative Site Number: 1005	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Kymab Limited	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Japan,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in EASI (Eczema Area and Severity Index) from Baseline	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	Baseline to Day 113
Secondary	Incidence of treatment-emergent adverse event		Baseline through Day 477
Secondary	Serum KY1005 concentration assessed throughout the study		Baseline through Day 477
Secondary	Percentage change in EASI (Eczema Area and Severity Index) from baseline to Day 169	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	Baseline to Day 169
Secondary	Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 113 and 169
Secondary	Percentage of patients with a response of IGA (Investigator Global Assessment) 0 or 1 and a reduction from baseline = 2 points	The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD.	At Days 113 and 169
Secondary	Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) = 4 with a baseline pruritus of = 4 from baseline	The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.	Days 113 and 169
Secondary	Absolute change from Baseline in EASI (Eczema Area and Severity Index)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85, 113, 141 and 169
Secondary	Percentage change from Baseline in EASI (Eczema Area and Severity Index)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85 and 141
Secondary	Percentage of patients with at least a 50% reduction from Baseline in EASI (EASI 50)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85, 113, 141 and 169
Secondary	Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85, and 141
Secondary	Percentage of patients with at least a 90% reduction from Baseline in EASI (EASI 90)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85, 113, 141 and 169
Secondary	Percentage of patients with a 100% reduction from Baseline in EASI (EASI 100)	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.	At Days 15, 29, 57, 85, 113, 141 and 169
Secondary	Change in IGA (Investigator Global Assessment) from Baseline	The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD	Baseline to day 113 and over time up to Day 365
Secondary	Percentage of patients with a score of IGA (Investigator Global Assessment) 0 or 1 and a reduction from Baseline of = 2 points	The IGA is a five-point scale that provides a global clinical assessment of AD (Atopic Dermatitis) severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD	At Days 15, 29, 57, 85, and 141
Secondary	Absolute and Percentage change in SCORAD (SCORing Atopic Dermatitis) Index from Baseline	SCORAD was used to assess the extent and severity of AD (Atopic Dermatitis). Extent and severity of eczema as well as subjective assessment of symptoms were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease)	Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in affected BSA from Baseline		Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in Patient Oriented Eczema Measure (POEM) from Baseline	POEM is a 7-item (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) questionnaire to assess frequency of disease symptoms with a scoring system of 0 to 28. The higher score indicating higher severity	Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in Dermatology Life Quality Index (DLQI) from Baseline	DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.	Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in Atopic Dermatitis Control Tool (ADCT) from Baseline	ADCT is a questionnaire to assess patient-self-perceived control of their eczema with a total score from 0 to 24; higher scores indicate lower AD control	Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in Hospital Anxiety and Depression Scale (HADS) from Baseline	HADS is a fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression	Baseline to Day 169 and over time up to Day 365
Secondary	Absolute and Percentage change in weekly average of pruritus Numerical Rating Scale (NRS) from Baseline	The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.	Baseline to Day 169 and over time up to Day 365
Secondary	Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) = 3 with a baseline pruritus NRS = 3 from baseline	The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.	Baseline to Days 113 and 169
Secondary	Incidence of positive anti-Ky1005 antibody response		Baseline through Day 477
Secondary	Time to loss of EASI 75	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition.	Week 24 to Day 365
Secondary	Time to loss of IGA 0/1 (Patients with a response of 0 or 1 in IGA)	The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD.	Week 24 to Day 365
Secondary	Time to loss of EASI 50	The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition.	Week 24 to Day 365