Clinical trial NCT04007198: A Study of Itolizumab (EQ001) to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity in Uncontrolled Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: moderate-to-severe asthma
Lead sponsor: Equillium
Sponsor class: INDUSTRY
Collaborators: name: Biocon Limited
name: Equillium AUS Pty Ltd
First posted: 2019-07-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: up to 5 cohorts of 8 patients randomized 3:1 with ascending doses
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Is male or female, age ≥ 18 and ≤ 75 years
2. 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
3. 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)
4. Has a history of clinically diagnosed asthma, which could include a history of FEV1 reversibility and/or positive bronchial challenge test
5. 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:

1. 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)
2. Has a body mass index \> 36 kg/m2
3. 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)
4. 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)
5. 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)
6. 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
7. 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
8. 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:

   1. Affect the subject's safety
   2. Influence the findings of the study or data interpretation
   3. Impede the subject's ability to complete the study
9. Has undergone bronchial thermoplasty
10. 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
11. 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)
12. 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

Primary outcomes:
measure: Number of Treatment Emergent Adverse Events
timeFrame: Study Day 85
Secondary outcomes:
measure: Time to Maximum EQ001serum Concentration, Tmax
timeFrame: Study Day 85
measure: Maximum EQ001 Serum Drug Concentration, Cmax
timeFrame: Study Day 85
measure: Minimum EQ001 Serum Drug Concentration, Cmin
timeFrame: Study Day 85
measure: Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)
timeFrame: Study Day 85
measure: Volume of Distribution of EQ001, Vd
timeFrame: Study Day 85
measure: Clearance, Cl
timeFrame: Study Day 85
measure: Inflammatory Markers
timeFrame: Study Day 85
measure: CD6 Receptor Expression
timeFrame: Study Day 85
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Flinders Medical Centre
city: Box Hill
country: Australia
facility: Box Hill Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Kanwal
country: Australia
facility: Paratus Clinical Research Central Coast
city: Kent Town
country: Australia
facility: Respiratory Clinical Trials
city: Murdoch
country: Australia
facility: TrialsWest
city: Parkville
country: Australia
facility: Melbourne Health
city: Sydney
country: Australia
facility: Paratus Clinical Research Western Sydney
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Auckland
country: New Zealand
facility: Respiratory Research, Greenland Clinical Centre
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Greenlane
country: New Zealand
facility: The New Zealand Respiratory & Sleep Institute
city: Wellington
country: New Zealand
facility: Medical Research Institute of New Zealand
Study officials:
affiliation: Melbourne Health
name: Jo A Douglass, MD
role: PRINCIPAL_INVESTIGATOR
References: