EQUIP: A Study of Itolizumab (EQ001) to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity in Uncontrolled Asthma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EQ001 EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses. |
Drug: EQ001
Itolizumab [Bmab 600]
Other Names:
|
| Placebo Comparator: EQ001 Placebo Placebo administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses. |
Drug: EQ001 Placebo
EQ001 Placebo
|
Outcome Measures
Primary Outcome Measures
- Incidence 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
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Flinders Medical Centre | Adelaide | Australia | ||
| 2 | Box Hill Hospital | Box Hill | Australia | ||
| 3 | Monash Medical Centre | Clayton | Australia | ||
| 4 | Paratus Clinical Research Central Coast | Kanwal | Australia | ||
| 5 | Respiratory Clinical Trials | Kent Town | Australia | ||
| 6 | TrialsWest | Murdoch | Australia | ||
| 7 | Melbourne Health | Parkville | Australia | ||
| 8 | Paratus Clinical Research Western Sydney | Sydney | Australia | ||
| 9 | The Queen Elizabeth Hospital | Woodville | Australia | ||
| 10 | Respiratory Research, Greenland Clinical Centre | Auckland | New Zealand | ||
| 11 | Dunedin Hospital | Dunedin | New Zealand | ||
| 12 | The New Zealand Respiratory & Sleep Institute | Greenlane | New Zealand | ||
| 13 | Medical Research Institute of New Zealand | Wellington | New Zealand |
Sponsors and Collaborators
- Equillium
- Biocon Limited
- Equillium AUS Pty Ltd
Investigators
- Principal Investigator: Jo A Douglass, MD, Melbourne Health
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- EQ001-19-001