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

• ClinicalTrials.gov Identifier: NCT04007198
• Recruitment Status: Recruiting
• First Posted: July 5, 2019
• Last Update Posted: January 13, 2020
• Sponsor: Equillium
• Collaborator: Biocon Limited
• Information provided by (Responsible Party): Equillium

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
Asthma	Drug: EQ001; Drug: EQ001 Placebo	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: up to 5 cohorts of 8 patients randomized 3:1 with ascending doses
• Masking: Quadruple (Participant, Care Provider, 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.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 20, 2019
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: December 31, 2020

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: Bmab600; Itolizumab
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 :

1. Incidence of Treatment Emergent Adverse Events [ Time Frame: 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 :

1. Time to maximum EQ001serum concentration, Tmax [ Time Frame: Study Day 85 ]
   Time to maximum EQ001 serum concentration, Tmax
2. Maximum EQ001 serum drug concentration, Cmax [ Time Frame: Study Day 85 ]
   Maximum EQ001 serum drug concentration, Cmax
3. Minimum EQ001 serum drug concentration, Cmin [ Time Frame: Study Day 85 ]
   Minimum EQ001 serum drug concentration prior to next dose, Cmin
4. Total EQ001 exposure across time, AUC (from zero to infinity) [ Time Frame: Study Day 85 ]
   Total EQ001 exposure across time, AUC (from zero to infinity)
5. Volume of distribution of EQ001, Vd [ Time Frame: Study Day 85 ]
   Volume of distribution of EQ001, Vd
6. Clearance, Cl [ Time Frame: Study Day 85 ]
   Clearance, Cl
7. Inflammatory Markers [ Time Frame: 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
8. CD6 receptor occupancy [ Time Frame: Study Day 85 ]
   the % levels of free versus EQ001-bound CD6 receptor on T cells

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 FEV1 reversibility of > 12% (% predicted increase) AND ≥ 200 mL (absolute increase) after administration of a short-acting beta agonist (200 to 400 mcg albuterol/salbutamol or equivalent) during the Screening Period or documented within the prior 2 years, or has a history of positive bronchial challenge test within the prior 2 years
5. Has a history of ≥ 1 clinically significant asthma exacerbation (see definition in Section 9.2.2) in the 12 months 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

Contacts and Locations

Contacts

Contact: Stephanie Leyva; 858 412 5302; clinicaltrials@equilliumbio.com

Locations

Australia

Flinders Medical Centre; Recruiting

Adelaide, Australia

Box Hill Hospital; Recruiting

Box Hill, Australia

Monash Medical Centre; Recruiting

Clayton, Australia

Respiratory Clinical Trials; Recruiting

Kent Town, Australia

TrialsWest; Recruiting

Murdoch, Australia

Melbourne Health; Recruiting

Parkville, Australia

The Queen Elizabeth Hospital; Recruiting

Woodville, Australia

New Zealand

Respiratory Research, Greenland Clinical Centre; Recruiting

Auckland, New Zealand

Dunedin Hospital; Recruiting

Dunedin, New Zealand

The New Zealand Respiratory & Sleep Institute; Recruiting

Greenlane, New Zealand

Sponsors and Collaborators

Equillium

Biocon Limited

Investigators

• Principal Investigator: Jo A Douglass, MD; Melbourne Health

More Information

Additional Information:

company website  Australia New Zealand Clinical Trials Registry 

• Responsible Party: Equillium
• ClinicalTrials.gov Identifier: NCT04007198
• Other Study ID Numbers: EQ001-19-001
• First Posted: July 5, 2019
• Last Update Posted: January 13, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Equillium:

moderate-to-severe asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases