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

Phase 1

Completed

• Conditions: Asthma
• Interventions: Drug: EQ001 Placebo; Drug: EQ001

• Registration Number: NCT04007198
• Lead Sponsor: Equillium

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.

Study Timeline

• Study Start: 2019-06-20
• Study First Submitted: 2019-06-27
• Study First Submitted QC: 2019-07-01
• Study First Posted: 2019-07-05
• Primary Completion: 2021-10-12
• Study Completion: 2021-10-12
• Results First Submitted: 2025-02-13
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-01
• Last Update Submitted: 2025-04-01
• Results First Posted: 2025-04-18
• Last Update Posted: 2025-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
EQ001 Placebo	EQ001 Placebo	Placebo administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses.
EQ001	EQ001	EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses.

Primary Outcome Measures

Name	Time	Method
Number of Treatment Emergent Adverse Events	Study Day 85	Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Secondary Outcome Measures

Name	Time	Method
Time to Maximum EQ001serum Concentration, Tmax	Study Day 85	Time to maximum EQ001 serum concentration, Tmax
Maximum EQ001 Serum Drug Concentration, Cmax	Study Day 85	Maximum EQ001 serum drug concentration, Cmax
Minimum EQ001 Serum Drug Concentration, Cmin	Study Day 85	Minimum EQ001 serum drug concentration prior to next dose, Cmin
Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)	Study Day 85	Total EQ001 exposure across time, AUC (from zero to infinity)
Volume of Distribution of EQ001, Vd	Study Day 85	Volume of distribution of EQ001, Vd
Clearance, Cl	Study Day 85	Clearance, Cl
Inflammatory Markers	Study Day 85	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
CD6 Receptor Expression	Study Day 85	the % levels of free versus EQ001-bound CD6 receptor on T cells

Trial Locations

Locations (13)

Monash Medical Centre; 🇦🇺 Clayton, Australia

Flinders Medical Centre; 🇦🇺 Adelaide, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Australia

Paratus Clinical Research Western Sydney; 🇦🇺 Sydney, Australia

The New Zealand Respiratory & Sleep Institute; 🇳🇿 Greenlane, New Zealand

Paratus Clinical Research Central Coast; 🇦🇺 Kanwal, Australia

Respiratory Clinical Trials; 🇦🇺 Kent Town, Australia

Melbourne Health; 🇦🇺 Parkville, Australia

Respiratory Research, Greenland Clinical Centre; 🇳🇿 Auckland, New Zealand

TrialsWest; 🇦🇺 Murdoch, Australia

The Queen Elizabeth Hospital; 🇦🇺 Woodville, Australia

Dunedin Hospital; 🇳🇿 Dunedin, New Zealand

Medical Research Institute of New Zealand; 🇳🇿 Wellington, New Zealand