Phase 2 N=81 Randomized Quadruple-blind Treatment

Anti-ST2 (MSTT1041A) in COPD (COPD-ST2OP)

COPD Exacerbation

Bottom Line

View on ClinicalTrials.gov: NCT03615040 ↗

Enrolled (actual)

Serious AEs

34.6%

Results posted

May 2022

Primary outcome: Primary: Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation). — 2.21; 2.67 Exacerbations — p=0.195

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: MSTT1041A (Drug); Placebo (Drug)
Age: Adult, Older Adult · 40+ yrs
Sex: All
Sponsor: University of Leicester
Primary completion: May 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation).	2.21; 2.67	0.195
SECONDARY Adverse Event Rate in the 48 Weeks of the Trial From First Dose	34; 28	—
SECONDARY Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose	12; 16	—
SECONDARY St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score	60.1; 58.4; 56.7; 58.9; 56.9; 59.9	0.039 sig
SECONDARY COPD Assessment Test (CAT) (Questionnaire)	22.1; 22.6; 22.2; 21.7; 22.0; 22.3	0.469
SECONDARY Modified Medical Research Council (mMRC) Dyspnea Scale	2.0; 2.0; 2.0; 2.0; 2.0; 2.0	0.90
SECONDARY Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores	142.7; 143.8; 129.3; 148.5; 139.5; 140.0	0.236
SECONDARY Sputum Purulence Colour Card	3.0; 3.0; 3.0; 3.0; 3.0; 3.0	0.84
SECONDARY Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio	49.0; 46.6; 51.0; 40.2	0.069
SECONDARY Post BD Forced Expiratory Volume in 1 Second (FEV1)	1.21; 1.14; 1.21; 1.09; 1.22; 1.14	0.094
SECONDARY Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume	7.5; 7.5; 7.6; 7.6; 4.5; 4.7	0.905
SECONDARY Blood Inflammatory Cell Differentials	8.2; 8.0; 7.5; 7.5; 8.0; 7.7	0.736
SECONDARY Sputum Inflammatory Cell Differentials: Eosinophils	1.42; 1.63; 0.43; 1.69; 0.41; 1.67	<0.001 sig
SECONDARY Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC	1.43; 0.94; 1.43; 0.86; 2.97; 2.17	0.362
SECONDARY Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted	55.9; 39.6; 56.5; 38.2; 88.5; 75.6	0.711
SECONDARY Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio	59.8; 61.3; 61.1; 65.2	0.201
SECONDARY Sputum Inflammatory Cell Differentials: Macrophages	8.9; 9.6; 8.6; 11.0; 9.0; 9.8	0.114
SECONDARY Sputum Inflammatory Cell Differentials: Epithelium	1.51; 1.59; 1.34; 2.06; 1.14; 1.91	0.215

Summary

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide. In contrast to other chronic diseases, COPD is increasing in prevalence and is projected to be the third-leading cause of death and disability worldwide by 2030. The costs to society for treating COPD are high, accounting for approximately 3.4% of the total health care budget of the European Union. Acute exacerbations of COPD (AECOPD) are responsible for a large portion of the economic burden of COPD. More than 500,000 hospitalisations and 100,000 deaths are attributed to AECOPD in the US each year. In addition to a substantial economic burden, AECOPD is also responsible for much of the morbidity and mortality from COPD. Interleukin-33 (IL-33) is an alarmin released from the epithelium following damage. IL-33 is an IL-1 family alarmin cytokine constitutively expressed at epithelial barrier surfaces where it is rapidly released from cells during tissue injury. IL-33 signals through a receptor complex of IL-1 receptor-like 1 (IL1RL1) (known as ST2) and IL-1 receptor accessory protein (IL1RAcP) to initiate MyD88-dependent inflammatory pathways. The role of the IL33/ST2 axis in COPD is uncertain. IL33 has been implicated in eosinophil recruitment to the airway and maturation in the bone marrow largely via its effects upon innate lymphoid cells. IL33 increased following experimental cold in asthma and thus might play a role in the consequent inflammatory response and possible susceptibility to secondary bacterial infection in obstructive lung disease. Both eosinophilic inflammation and viral infection drive COPD exacerbations and therefore targeting the IL33/ST2 axis might reduce COPD exacerbations. The main aim of this trial is to evaluate whether anti-ST2 will impact on airway inflammation in COPD and therefore reduce the frequency of exacerbations. For the purposes of this trial, exacerbations are defined as flare-ups of symptoms involving the use of healthcare resulting in treatment with steroids and/or antibiotics and/or hospitalisation or death due to COPD.

Eligibility Criteria

Inclusion Criteria

Symptoms typical of COPD when stable (baseline mMRC dyspnoea score ≥ 2)
GOLD COPD stage 2-4
Smoking pack years ≥ 10 years
Age > 40 years
Receiving standard-of-care drug therapy as per British Thoracic Society (BTS) guidance for COPD
A history of ≥ 2 moderate-to-severe exacerbations in the last 12 months.
Be able to give valid written consent; compliant with study procedures and study visits.
Able to understand written and spoken English

Exclusion Criteria

Significant known respiratory disorders other than COPD that in the view of the investigator will affect the study
Patients whose treatment is considered palliative (life expectancy <12 months)
Known hypersensitivity to the active substance of the investigational product (IP) or any of the excipients
Known history of anaphylaxis
Patients with a COPD exacerbation and/or pneumonia within the 4 weeks prior to visit 1
Have, in the opinion of investigator, uncontrolled co-morbid conditions, such as diabetes mellitus, hypertension and heart failure [e.g. New York Heart Association (NYHA) class III (e.g. less than ordinary activity causes fatigue, palpitation, or dyspnoea), and class IV (e.g. Symptoms of heart failure at rest)] that will affect the study.
Myocardial infarction, unstable angina or stroke within 12 month prior to screening
Diagnosis of malignancy within 5 years of visit 1 (except for excised localised carcinoma of skin not including malignant melanoma)
Clinically significant ECG changes, which in the opinion of investigator warrants further investigations
Laboratory abnormalities, which in the opinion of investigator warrants further investigations
Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
Pregnant, breastfeeding, or lactating women. Women of child-bearing potential (i.e. not surgically sterilised or post- menopausal) must have a negative blood serum pregnancy test performed at the screening visit and must agree to use two methods of birth control, (one of which must be a barrier method).
Participation in an interventional clinical study within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half- lives.
Upon questioning the patient has blood born infection (e.g. HIV, hepatitis B or C)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03615040). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.