Phase 2
N=137
A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis
Chronic Obstructive Pulmonary Disease (COPD) · Chronic Bronchitis
Bottom Line
View on ClinicalTrials.gov: NCT04631016 ↗Enrolled (actual)
137
Serious AEs
17.0%
Results posted
Feb 2025
Primary outcome: Primary: Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic — 0.019; -0.005 Litre — p=0.216
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tozorakimab (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- May 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic |
0.019; -0.005 | 0.216 |
| SECONDARY Serum Tozorakimab Concentration |
24604.70; 8041.59; 7548.78; 10789.81; 6410.05; 7289.36 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event |
28; 36 | 0.186 |
| SECONDARY Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score |
-6.09; -6.06 | — |
| SECONDARY Change From Baseline to Week 12 in Mean Breathlessness, Cough and Sputum Scale (BCSS) Score (Over the Previous 4 Weeks) |
-2.18; -2.18 | — |
| SECONDARY Change From Baseline to Week 12 in Cough Visual Analogue Scale (VAS) Score |
-17.21; -17.70 | — |
| SECONDARY Change From Baseline to Week 12 in Saint George's Respiratory Questionnaire (SGRQ) Total Score |
-9.177; -8.273 | — |
| SECONDARY Percentage of Participants With a Decrease in SGRQ Total Score of >= 4 Points From Baseline to Week 12 |
61.3; 61.5 | — |
| SECONDARY Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters |
0.008; -0.014; 0.015; -0.030; 0.006; -0.017 | — |
| SECONDARY Change From Baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX) |
-0.081; -0.267 | — |
| SECONDARY Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12 |
0.89; 0.83; 1.03; 0.61; 0.89; 0.84 | — |
| SECONDARY Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10% |
0.031; 0.006; -0.039; -0.018 | — |
| SECONDARY Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10% |
-0.015; -0.068; 0.074; -0.053 | — |
| SECONDARY Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10% |
-0.143; -0.056; -0.121; 0.046 | — |
| SECONDARY Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10% |
0.089; -0.121; 0.081; -0.094 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs) |
53; 50; 14; 9; 33; 24 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs Reported as TEAEs |
2; 3; 1; 0; 2; 3 | — |
| SECONDARY Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs |
0; 1; 0; 1; 0; 1 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs |
1; 0 | — |
| SECONDARY Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram |
0.9; 0.2 | — |
| SECONDARY Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level |
4.051; 1.948 | — |
| SECONDARY Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs |
17; 14; 1; 0 | — |
| SECONDARY Number of Participants Seropositive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) |
6; 6 | — |
Summary
This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult participants with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.
Eligibility Criteria
Inclusion Criteria
- Provision of informed consent.
- Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent form (ICF).
- Participants who are current or ex-smokers with a tobacco history of >= 10 pack-years.
- Participants who have a documented history of COPD for at least 1 year.
- Participants who have a post-BD FEV1/FVC = 20% and = 3 months/year in at least the 2 year period immediately prior to study visit 1 (SV1) (Screening).
- Participants who have an average BCSS score of >= 2 in cough and >= 2 in sputum domains assessed over 14 days preceding SV3.
- Participants who have a documented stable regimen of dual therapy or triple therapy for >= 3 months prior to enrolment; there should have been no change in treatment after the previous exacerbation prior to entering into the study. Where dual therapy consists of inhaled corticosteroids (ICS) + long-acting beta 2 agonist (LABA) or LABA + long-acting muscarinic receptor antagonist (LAMA), and triple therapy consists of ICS + LABA + LAMA.
- Participants who have a documented history of >= 1 moderate or severe AECOPD requiring systemic corticosteroids and/or antibiotics for at least 3 days duration (or 1 injection of depot formulation), or hospitalization for reason of AECOPD in the previous 24 months.
- Body mass index within the range 18 to 40 kg/m^2 (inclusive).
- Female participants of childbearing potential, must have negative pregnancy tests.
- Male and female participants must follow protocol contraceptive guidance.
Exclusion Criteria
- Participants with a positive diagnostic nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening. Participants with mild or asymptomatic disease could be rescreened.
- Participants with a significant coronavirus disease 2019 (COVID-19) illness within 6 months of enrolment.
- As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason which in the investigator's opinion makes it undesirable for the participant to participate in the study.
- Current or past diagnosis of asthma which persisted beyond age of 25 years.
- Clinically important pulmonary disease other than COPD, radiological findings, and/or laboratory findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
- Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1 of >= 400 mL or >= 25% of SV1 FEV1.
- Any other clinically relevant abnormal findings on physical examination, laboratory testing; or chest CT scan, which in the opinion of the investigator or medical monitor may compromise the safety of the participant in the study or interfere with evaluation of the study intervention or reduce the participant's ability to participate in the study.
Chest CT scan findings requiring further investigation or repeat CT surveillance before SV14.
- A family history of heart failure.
- A LVEF < 45% measured by echocardiogram.
- History of a clinically significant infection (viral, bacterial, or fungal) within 4 weeks.
- History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past 2 years prior to screening.
- Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- Evidence of active or untreated latent tuberculosis (TB).
- Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up.
- Participants currently receiving background therapy that is not approved by regulatory authorities in the country of study for COPD are not eligible for the study.
- History of treatment with cardiotoxic medications (eg, as part of cancer therapy) including thiazolidinedione's.
- Treatment with broad spectr
Data sourced from ClinicalTrials.gov (NCT04631016). 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.