A Study of Itolizumab (EQ001) to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity in Uncontrolled Asthma

Study Overview
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Brief Summary
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This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of itolizumab (EQ001) in subjects with moderate-to-severe asthma.

Detailed Description
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The study will enroll up to 40 subjects, with up to 5 dose escalating cohorts of 8 patients enrolled in a 3:1 ratio. Subjects will receive either itolizumab or placebo administered subcutaneously every two weeks (over 8 weeks) for a total of 5 doses with 4 weeks of follow-up.

Official Title
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A Phase 1b Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Moderate-to-Severe Uncontrolled Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: EQ001
* Drug: EQ001 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female, age ≥ 18 and ≤ 75 years Has a documented clinical diagnosis of moderate-to-severe uncontrolled asthma requiring moderate- or high-dose inhaled CS (ICS; ≥ 250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) and one or more additional controller medications (inhaled LABA or anticholinergic or LTA) for ≥ 3 months, with a stable dose ≥1 month prior to the initial Screening Visit Has a prebronchodilator forced expiratory volume in 1 second (FEV1) ≥ 40% and ≤ 90% of predicted value during the Screening Period, despite use of a moderate- or high-dose ICS and one or more additional controller medications (inhaled LABA or anticholinergic or LTA) Has a history of clinically diagnosed asthma, which could include a history of FEV1 reversibility and/or positive bronchial challenge test Has a history of ≥ 1 clinically significant asthma exacerbation prior to the initial Screening Visit, despite use of a moderate- or high dose ICS and one or more additional controller medications at the time the exacerbation(s) occurred Exclusion Criteria: Is a current or former smoker with a smoking history of ≥10 pack-years (number of pack-years = number of cigarettes per day/20 × number of years smoked; a former smoker is defined as a subject who stopped smoking ≥ 6 months prior to the Screening Visit) Has a body mass index > 36 kg/m2 Has a documented history or radiological evidence of a clinically important lung condition other than asthma (eg, α1 antitrypsin deficiency, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, pulmonary fibrosis, allergic bronchopulmonary mycosis, or lung cancer) Has a respiratory tract infection (RTI) within 4 weeks before the initial Screening Visit, or during the Screening Period (these subjects may be re-screened following complete resolution of their RTI) Has an asthma exacerbation within 4 weeks before the initial Screening Visit, or during the Screening Period (these subjects may be re-screened following complete resolution of their exacerbation) Has a diagnosis of currently active malignancy; subjects with a medical history of basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the uterine cervix are eligible; subjects with a medical history of other malignancies are eligible if the subject is in remission and curative therapy was completed ≥ 2 years prior to the initial Screening Visit Has a history or presence of clinically concerning cardiac arrythmias, atrial fibrillation, New York Heart Association Class III or IV heart failure, or prolonged QT or corrected QT interval > 500 milliseconds (ms) at the Screening Visit Has any disorder (including, but not limited to, cardiovascular [CV], gastrointestinal [GI], hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment) that is not stable in the opinion of the investigator and/or could: Affect the subject's safety Influence the findings of the study or data interpretation Impede the subject's ability to complete the study Has undergone bronchial thermoplasty Has a history of substance abuse (including alcohol) that may, in the investigator's judgment, increase the risk to the subject of participation in the study Has used monoclonal antibody (mAb) therapy for the management of asthma or any other condition within 3 months prior to the initial Screening Visit (these subjects may be re-screened following the 3 month period) Has required an oral corticosteroid burst within 1 month prior to the initial Screening Visit or during the Screening Period (these subjects may be re-screened following the 1 month period); maintenance oral corticosteroids ≤ 10 mg/d prednisone or equivalent is permitted

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: Sequential Assignment
Interventional Model Description: up to 5 cohorts of 8 patients randomized 3:1 with ascending doses
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EQ001<br>EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses. | Drug: EQ001<br>* Itolizumab [Bmab 600]<br>* Other names: Itolizumab;|
| Placebo Comparator: EQ001 Placebo<br>Placebo administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses. | Drug: EQ001 Placebo<br>* EQ001 Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | Study Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum EQ001serum concentration, Tmax | Time to maximum EQ001 serum concentration, Tmax | Study Day 85 | 
| Maximum EQ001 serum drug concentration, Cmax | Maximum EQ001 serum drug concentration, Cmax | Study Day 85 | 
| Minimum EQ001 serum drug concentration, Cmin | Minimum EQ001 serum drug concentration prior to next dose, Cmin | Study Day 85 | 
| Total EQ001 exposure across time, AUC (from zero to infinity) | Total EQ001 exposure across time, AUC (from zero to infinity) | Study Day 85 | 
| Volume of distribution of EQ001, Vd | Volume of distribution of EQ001, Vd | Study Day 85 | 
| Clearance, Cl | Clearance, Cl | Study Day 85 | 
| Inflammatory Markers | Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein | Study Day 85 | 
| CD6 receptor expression | the % levels of free versus EQ001-bound CD6 receptor on T cells | Study Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate-to-severe asthma