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

Study Overview
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Brief Summary
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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 protocol at either Day 169 depending on responder status or no later than Day 365 due to loss of clinical response.

Official Title
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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

Conditions
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Eczema, Atopic Dermatitis

Intervention / Treatment
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* Drug: KY1005
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KY1005 Dose Level 1<br>Every 4 weeks | Drug: KY1005<br>* Pharmaceutical form: Injection solution Route of administration: Subcutaneous<br>* Other names: A human anti-OX40 ligand monoclonal antibody;|
| Experimental: KY1005 Dose Level 2<br>Every 4 weeks | Drug: KY1005<br>* Pharmaceutical form: Injection solution Route of administration: Subcutaneous<br>* Other names: A human anti-OX40 ligand monoclonal antibody;|
| Experimental: KY1005 Dose Level 3<br>Every 4 weeks | Drug: KY1005<br>* Pharmaceutical form: Injection solution Route of administration: Subcutaneous<br>* Other names: A human anti-OX40 ligand monoclonal antibody;|
| Experimental: KY1005 Dose Level 4<br>Every 4 weeks | Drug: KY1005<br>* Pharmaceutical form: Injection solution Route of administration: Subcutaneous<br>* Other names: A human anti-OX40 ligand monoclonal antibody;|
| Placebo Comparator: Placebo<br>Every 4 weeks | Drug: Placebo<br>* Pharmaceutical form: Injection solution Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse event |  | Baseline through Day 477 | 
| Serum KY1005 concentration assessed throughout the study |  | Baseline through Day 477 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Absolute and Percentage change in affected BSA from Baseline |  | Baseline to Day 169 and over time up to Day 365 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Incidence of positive anti-Ky1005 antibody response |  | Baseline through Day 477 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KY1005, Monoclonal Antibody, Atopic Dermatitis, Atopic Eczema, OX40L