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

Asthma Clinical Trial

— EQUIP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04007198
• Other study ID #: EQ001-19-001
• Status: Completed
• Phase: Phase 1
• Start date: June 20, 2019
• Est. completion date: October 12, 2021

Study information

• Verified date: January 2022
• Source: Equillium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 12, 2021
• Est. primary completion date: October 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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, a1 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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• EQ001
Itolizumab [Bmab 600]
• EQ001 Placebo
EQ001 Placebo

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide
Australia	Box Hill Hospital	Box Hill
Australia	Monash Medical Centre	Clayton
Australia	Paratus Clinical Research Central Coast	Kanwal
Australia	Respiratory Clinical Trials	Kent Town
Australia	TrialsWest	Murdoch
Australia	Melbourne Health	Parkville
Australia	Paratus Clinical Research Western Sydney	Sydney
Australia	The Queen Elizabeth Hospital	Woodville
New Zealand	Respiratory Research, Greenland Clinical Centre	Auckland
New Zealand	Dunedin Hospital	Dunedin
New Zealand	The New Zealand Respiratory & Sleep Institute	Greenlane
New Zealand	Medical Research Institute of New Zealand	Wellington

Sponsors (3)

Lead Sponsor	Collaborator
Equillium	Biocon Limited, Equillium AUS Pty Ltd

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

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

External Links

•   Australia New Zealand Clinical Trials Registry
•   company website