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

Kymab Limited390 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

390

Conditions

Eczema Atopic Dermatitis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (103)

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

Outcomes

Primary Outcomes

Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 16 (Part 1)

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.

Time frame: Baseline to week 16

Secondary Outcomes

Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 24 (Part 1)

Time frame: Baseline to week 24

Percentage of Participants With at Least a 75% Reduction From Baseline in EASI (EASI 75) at Week 16 and Week 24 (Part 1)

Time frame: Baseline to week 16 and week 24

Percentage of Participants With a Response of IGA (Investigator Global Assessment) 0 or 1 and a Reduction From Baseline ≥ 2 Points (Part 1)

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.

Time frame: Baseline to week 16 and week 24

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)

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'.

Time frame: Baseline to week 16 and week 24

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)

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'.

Time frame: 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

Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20 and 24

Percentage Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)

Time frame: Baseline to weeks 2,4, 8,12,16, 20 and 24

Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52

Percentage Change From Baseline in EASI (Eczema Area and Severity Index) (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52

Percentage of Participants With at Least a 50% Reduction From Baseline in EASI (EASI 50) (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20 and 24

Percentage of Participants With at Least a 75% Reduction From Baseline in EASI (EASI 75) (Part 1)

Time frame: Baseline at weeks 2, 4, 8, 12, 16, 20 and 24

Percentage of Participants With at Least a 90% Reduction From Baseline in EASI (EASI 90) (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20 and 24

Percentage of Participants With a 100% Reduction From Baseline in EASI (EASI 100) (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20 and 24

Change in IGA (Investigator Global Assessment) From Baseline to (Week 24) (Part 1)

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

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20, & 24

Change in IGA (Investigator Global Assessment) From Baseline (Part 2)

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

Time frame: Baseline to weeks 24, 28, 31, 36, 40, 44, 48 & 52

Percentage of Participants With a Score of IGA (Investigator Global Assessment) 0 or 1 and a Reduction From Baseline of ≥ 2 Points (Part 1)

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

Time frame: Baseline to weeks 2, 4, 8,12,16,20 & 24

Absolute Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 1)

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)

Time frame: Baseline to weeks 4, 8, 12, 16, 20 & 24

Absolute Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 2)

Time frame: Baseline to week 24, 28, 32, 36, 40, 44, 48 & 52

Percentage Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 1)

Time frame: Baseline to weeks 4, 8, 12, 16, 20, & 24

Percentage Change in SCORAD (SCORing Atopic Dermatitis) Index From Baseline (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52

Absolute Change in Affected Body Surface Area (BSA) From Baseline (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20, & 24

Absolute Change in Affected BSA From Baseline (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52

Percentage Change in Affected BSA From Baseline (Part 1)

Time frame: Baseline to weeks 2, 4, 8, 12, 16, 20, & 24

Percentage Change in Affected BSA From Baseline (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52

Absolute Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 1)

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

Time frame: Baseline to weeks 4, 8, 12, 16, 20, & 24

Absolute Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 2)

Time frame: Baseline to weeks 24, 32, 36, 40, 44, 48 & 52

Percentage Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 1)

Time frame: Baseline to weeks 4, 8, 12, 16, 20, & 24

Percentage Change in Patient Oriented Eczema Measure (POEM) From Baseline (Part 2)

Time frame: Baseline to weeks 24, 32, 36, 40. 44, 48, & 52

Absolute Change in Dermatology Life Quality Index (DLQI) From Baseline (Parts 1)

DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.

Time frame: Baseline to weeks 2, 8, 16, 20, & 24

Absolute Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 2)

DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52

Percentage Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 1)

DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.

Time frame: Baseline to weeks 2, 8, 16, 20, & 24

Percentage Change in Dermatology Life Quality Index (DLQI) From Baseline (Part 2)

DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48, & 52

Absolute Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 1)

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

Time frame: Baseline to weeks 16, & 24

Absolute Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 2)

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

Time frame: Baseline to weeks 24, 36 & 52

Percentage Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 1)

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

Time frame: Baseline to weeks 16, & 24

Percentage Change in Atopic Dermatitis Control Tool (ADCT) From Baseline (Part 2)

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

Time frame: Baseline to weeks 24, 36 & 52

Absolute Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 1)

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.

Time frame: Baseline to weeks 8 16, 20, & 24

Absolute Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52

Percentage Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 1)

Time frame: Baseline to weeks 8, 16, 20, & 24

Percentage Change in Hospital Anxiety and Depression Scale (HADS) From Baseline (Part 2)

Time frame: Baseline to weeks 24, 28, 32, 36, 40, 44, 48 & 52

Absolute Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 1)

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'.

Time frame: 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

Absolute Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 2)

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'.

Time frame: 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

Percent Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 1)

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'.

Time frame: 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

Percent Change in Weekly Average of Pruritus Numerical Rating Scale (NRS) From Baseline (Part 2)

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'.

Time frame: 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

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)

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'.

Time frame: 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

Incidence Rate of Loss of EASI 50 (Part 2)

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.

Time frame: Week 24 to week 52

Incidence Rate of Loss of EASI 75 (Part 2)

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.

Time frame: Week 24 to week 52

Incidence Rate of Loss of IGA 0/1 (Part 2)

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.

Time frame: Week 24 to week 68

Serum KY1005 Concentration Assessed Throughout the Study (Part 1)

Time frame: Baseline and at weeks 1, 2, 4, 8, 12, 16, 17, 20, & 24

Serum KY1005 Concentration Assessed Throughout the Study (Part 2)

Time frame: Baseline and at weeks 24, 25, 28, 32, 36, 40, 44, 48, & 52

Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Any Serious TEAE (Part 1)

Time frame: Baseline through week 24

Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Any Serious TEAE (Part 2)

Time frame: Week 24 through week 68

Percentage of Participants With Treatment-emergent ADA (Part 1)

Time frame: Baseline through week 24

Percentage of Participants With Treatment-emergent ADA (Part 2)

Time frame: Baseline through week 68