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

Phase 2

Completed

Conditions: Atopic Dermatitis
Eczema

Interventions: Drug: Amlitelimab
Drug: Placebo
Drug: KY1005

Registration Number: NCT05131477

Lead Sponsor: Kymab Limited

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 Long-Term Extension (LTE) protocol (NCT05492578) at either Day 169 depending on responder status or no later than Day 365 due to loss of clinical response.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 390

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.
Eczema Area and Severity Index (EASI) of 12 or higher at the Screening Visit and 16 or higher at Baseline.
Investigator's Global Assessment (IGA) Scale of 3 or 4 at Baseline.
AD involvement of 10% or more of body surface area (BSA) at Baseline.
Baseline worst/maximum pruritus Numeric Rating Scale (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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
250mg (500mg Loading Dose) KY1005	Amlitelimab	Every 4 weeks
250mg (No Loading Dose) KY1005	Amlitelimab	Every 4 weeks
125mg KY1005	Amlitelimab	Every 4 weeks
62.5mg KY1005	Amlitelimab	Every 4 weeks
Placebo	Placebo	Every 4 weeks
Placebo	Placebo	Every 4 weeks
KY1005 Dose Level 1	KY1005	Every 4 weeks
KY1005 Dose Level 2	KY1005	Every 4 weeks
KY1005 Dose Level 3	KY1005	Every 4 weeks
KY1005 Dose Level 4	KY1005	Every 4 weeks

Primary Outcome Measures

Name	Time	Method
Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 16 (Part 1)	Baseline to week 16	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.

Secondary Outcome Measures

Name	Time	Method
Percentage Change in Affected BSA From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52
Percentage of Participants With at Least a 90% Reduction From Baseline in EASI (EASI 90) (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With Improvement (Reduction) of Weekly Average of Pruritus NRS (Numerical Rating Scale) ≥ 4 With a Baseline Pruritus of ≥ 4 From Baseline (Part 1)	Baseline to week 16 and week 24	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'.
Percentage of Participants With Improvement (Reduction) of Weekly Average of Pruritus NRS (Numerical Rating Scale) ≥ 4 With a Baseline Pruritus of ≥ 4 From Baseline (Part 2)	Baseline to weeks week 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, & 52	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'.
Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With a 100% Reduction From Baseline in EASI (EASI 100) (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 1)	Baseline to weeks 4, 8, 12, 16, 20, & 24	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)
Percentage Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52	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)
Absolute Change in Affected Body Surface Area (BSA) From Baseline (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20, & 24
Percentage Change in Affected BSA From Baseline (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20, & 24
Percentage Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 1)	Baseline to weeks 2, 8, 16, 20, & 24	DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.
Percentage Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52	DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.
Absolute Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 1)	Baseline to weeks 16, & 24	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
Percentage Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 1)	Baseline to weeks 16, & 24	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
Percentage Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 2)	Baseline to weeks 24, 36 & 52	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
Percentage Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 1)	Baseline to weeks 8, 16, 20, & 24	The HADS is 14-item questionnaire with two subscales: anxiety \& depression. Each subscale (anxiety \& depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state.
Percentage Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52	The HADS is 14-item questionnaire with two subscales: anxiety \& depression. Each subscale (anxiety \& depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state.
Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 24 (Part 1)	Baseline to week 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With at Least a 75% Reduction From Baseline in EASI (EASI 75) at Week 16 and Week 24 (Part 1)	Baseline to week 16 and week 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With a Response of IGA (Investigator Global Assessment) 0 or 1 and a Reduction From Baseline ≥ 2 Points (Part 1)	Baseline to week 16 and week 24	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,1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe AD.
Percentage Change From Baseline in EASI (Eczema Area and Severity Index) (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With at Least a 75% Reduction From Baseline in EASI (EASI 75) (Part 1)	Baseline at weeks 2, 4, 8, 12, 16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Absolute Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 1)	Baseline to weeks 4, 8, 12, 16, 20, & 24	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
Percent Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 2)	Baseline to weeks 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, & 52	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'.
Percentage Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)	Baseline to weeks 2,4, 8,12,16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Change in IGA (Investigator Global Assessment) From Baseline to (Week 24) (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20, & 24	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, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe AD
Percentage of Participants With a Score of IGA (Investigator Global Assessment) 0 or 1 and a Reduction From Baseline of ≥ 2 Points (Part 1)	Baseline to weeks 2, 4, 8,12,16,20 & 24	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, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe AD
Absolute Change in Affected BSA From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52
Percentage Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 2)	Baseline to weeks 24, 32, 36, 40. 44, 48, & 52	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
Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Percentage of Participants With at Least a 50% Reduction From Baseline in EASI (EASI 50) (Part 1)	Baseline to weeks 2, 4, 8, 12, 16, 20 and 24	Eczema Area and Severity Index-The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD with scores from 0 to 72. Higher scores indicate worse condition.
Absolute Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 1)	Baseline to weeks 4, 8, 12, 16, 20 & 24	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)
Absolute Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 2)	Baseline to week 24, 28, 32, 36, 40, 44, 48 & 52	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)
Absolute Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 2)	Baseline to weeks 24, 32, 36, 40, 44, 48 & 52	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
Percentage Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 1)	Baseline to weeks 4, 8, 12, 16, 20, & 24	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
Absolute Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 2)	Baseline to weeks 24, 36 & 52	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
Absolute Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 1)	Baseline to weeks 8 16, 20, & 24	The HADS is 14-item questionnaire with two subscales: anxiety \& depression. Each subscale (anxiety \& depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state.
Change in IGA (Investigator Global Assessment) From Baseline (Part 2)	Baseline to weeks 24, 28, 31, 36, 40, 44, 48 & 52	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, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe AD
Absolute Change in Dermatology Life Quality Index (DLQI) From Baseline (Parts 1)	Baseline to weeks 2, 8, 16, 20, & 24	DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.
Absolute Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52	DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.
Absolute Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 2)	Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52	The HADS is 14-item questionnaire with two subscales: anxiety \& depression. Each subscale (anxiety \& depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state.
Incidence Rate of Loss of EASI 75 (Part 2)	Week 24 to week 52	The incidence rate of loss of EASI 75 is calculated for participants who achieved EASI 75 at re-randomization (week 24). The incidence rate is computed as the number of participants losing EASI 75 divided by total follow-up time. The follow-up time is defined as the duration from re-randomization (week 24) to either the first event date (loss of EASI 75) or censoring date for participants who had no events. The censoring date is defined as the earliest occurrence of: use of rescue medications and/or selected prohibited medications/ procedures impacting efficacy, or study discontinuation/ completion.
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Any Serious TEAE (Part 1)	Baseline through week 24
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Any Serious TEAE (Part 2)	Week 24 through week 68
Percentage of Participants With Treatment-emergent ADA (Part 2)	Baseline through week 68
Absolute Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 1)	Baseline to weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, & 24	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'.
Absolute Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 2)	Baseline to weeks 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, & 52	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'.
Percent Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 1)	Baseline to weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 & 24	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'.
Incidence Rate of Loss of IGA 0/1 (Part 2)	Week 24 to week 68	The incidence rate of loss of IGA 0/1 is calculated for participants who achieved IGA 0/1 at re-randomization (week 24). The incidence rate is computed as the number of participants losing IGA 0/1 divided by total follow-up time. The follow-up time is defined as the duration from re-randomization (week 24) to either the first event date (loss of IGA 0/1) or censoring date for participants who had no events. The censoring date is defined as the earliest occurrence of: use of rescue medications and/or selected prohibited medications/ procedures impacting efficacy, or study discontinuation/ completion.
Percentage of Participants With Improvement (Reduction) of Weekly Average of Pruritus NRS (Numerical Rating Scale) ≥ 3 With a Baseline Pruritus NRS ≥ 3 From Baseline (Part 1)	Baseline to weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, & 24	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'.
Incidence Rate of Loss of EASI 50 (Part 2)	Week 24 to week 52	The incidence rate of loss of EASI 50 is calculated for participants who achieved EASI 50 at re-randomization (week 24). The incidence rate is computed as the number of participants losing EASI 50 divided by total follow-up time. The follow-up time is defined as the duration from re-randomization (week 24) to either the first event date (loss of EASI 50) or censoring date for participants who had no events. The censoring date is defined as the earliest occurrence of: use of rescue medications and/or selected prohibited medications/ procedures impacting efficacy, or study discontinuation/ completion.
Serum KY1005 Concentration Assessed Throughout the Study (Part 1)	Baseline and at weeks 1, 2, 4, 8, 12, 16, 17, 20, & 24
Serum KY1005 Concentration Assessed Throughout the Study (Part 2)	Baseline and at weeks 24, 25, 28, 32, 36, 40, 44, 48, & 52
Percentage of Participants With Treatment-emergent ADA (Part 1)	Baseline through week 24

Trial Locations

Locations (101): Investigative Site Number: 1018
🇺🇸
Fremont, California, United States
Investigative site #1022
🇺🇸
Sacramento, California, United States
Investigative Site Number: 1006
🇺🇸
Boca Raton, Florida, United States
Investigative Site Number: 1001
🇺🇸
Clearwater, Florida, United States
Investigative Site Number: 1019
🇺🇸
Coral Gables, Florida, United States
Investigative Site Number: 1007
🇺🇸
Miami, Florida, United States
Investigative Site Number: 1013
🇺🇸
Tampa, Florida, United States
Investigative Site Number: 1004
🇺🇸
Savannah, Georgia, United States
Investigative Site Number: 1010
🇺🇸
Clarksville, Indiana, United States
Investigative Site Number: 1015
🇺🇸
Indianapolis, Indiana, United States
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Investigative Site Number: 1018
🇺🇸Fremont, California, United States