Asthma
Conditions
Keywords
moderate-to-severe asthma
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.
Interventions
DRUGEQ001
Itolizumab \[Bmab 600\]
DRUGEQ001 Placebo
EQ001 Placebo
Sponsors
Biocon Limited
Equillium AUS Pty Ltd
Equillium
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study site, participant and most vendors will be blinded. The site's pharmacist or designee will be unblinded to prepare the study drug. Relevant vendors including PK will be unblinded.
Intervention model description
up to 5 cohorts of 8 patients randomized 3:1 with ascending doses
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Time to Maximum EQ001serum Concentration, Tmax | Study Day 85 | Time to maximum EQ001 serum concentration, Tmax |
| 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 |
| Volume of Distribution of EQ001, Vd | Study Day 85 | Volume of distribution of EQ001, Vd |
Countries
Australia, New Zealand
Participant flow
Pre-assignment details
Cohorts for dose 2.4mg/kg and 3.2mg/kg were not conducted. Data for placebo subjects in cohort for 0.8mg/kg and 1.6mg/kg were pooled in analysis.
Participants by arm
| Arm | Count |
|---|---|
| EQ001 0.8mg/kg EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses at 0.8mg/kg.
EQ001: Itolizumab \[Bmab 600\] | 7 |
| EQ001 Placebo Placebo administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses.
EQ001 Placebo: EQ001 Placebo | 4 |
| EQ001 1.6mg/kg EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 5 doses at 1.6mg/kg.
EQ001: Itolizumab \[Bmab 600\] | 7 |
| Total | 18 |
Baseline characteristics
| Characteristic | EQ001 0.8mg/kg | Total | EQ001 1.6mg/kg | EQ001 Placebo |
|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 15.59 | 52.2 years STANDARD_DEVIATION 14.84 | 50.1 years STANDARD_DEVIATION 18.53 | 56.0 years STANDARD_DEVIATION 6.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 18 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 14 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Australia | 6 participants | 16 participants | 6 participants | 4 participants |
| Region of Enrollment New Zealand | 1 participants | 2 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 4 |
| other Total, other adverse events | 6 / 7 | 7 / 7 | 1 / 4 |
| serious Total, serious adverse events | 0 / 7 | 1 / 7 | 0 / 4 |
Outcome results
Primary
Number 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.
Time frame: Study Day 85
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EQ001 0.8mg/kg | Number of Treatment Emergent Adverse Events | 6 Participants |
| EQ001 Placebo | Number of Treatment Emergent Adverse Events | 1 Participants |
| EQ001 1.6mg/kg | Number of Treatment Emergent Adverse Events | 7 Participants |
Secondary
CD6 Receptor Expression
the % levels of free versus EQ001-bound CD6 receptor on T cells
Time frame: Study Day 85
Secondary
Clearance, Cl
Clearance, Cl
Time frame: Study Day 85
Secondary
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
Time frame: Study Day 85
Secondary
Maximum EQ001 Serum Drug Concentration, Cmax
Maximum EQ001 serum drug concentration, Cmax
Time frame: Study Day 85
Secondary
Minimum EQ001 Serum Drug Concentration, Cmin
Minimum EQ001 serum drug concentration prior to next dose, Cmin
Time frame: Study Day 85
Secondary
Time to Maximum EQ001serum Concentration, Tmax
Time to maximum EQ001 serum concentration, Tmax
Time frame: Study Day 85
Secondary
Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)
Total EQ001 exposure across time, AUC (from zero to infinity)
Time frame: Study Day 85
Secondary
Volume of Distribution of EQ001, Vd
Volume of distribution of EQ001, Vd
Time frame: Study Day 85