A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Phase I study to evaluate the safety and tolerability of single ascending intravenous doses of MEDI2338 in subjects with stable, mild to moderate chronic obstructive pulmonary disease (COPD).

Official Title
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A Phase 1, Single Ascending Dose Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Biological: MEDI2338
* Biological: MEDI2338
* Biological: MEDI2338
* Biological: MEDI2338
* Biological: MEDI2338
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 40 years at time of screening. Females of non-childbearing potential defined as surgically sterile or at least 2 years postmenopausal. Males, unless surgically sterile, must use 2 highly effective methods of birth control from screening through end of trial. A diagnosis of mild to moderate COPD. Cigarette smoking history of ≥10 pack years. Ability to understand and comply with protocol requirements, instructions and restrictions. COPD symptoms adequately controlled on a therapeutic regimen that has not changed in the 4 weeks prior to screening. Exclusion Criteria: Current diagnosis of any respiratory condition other than COPD. Active or history of any disease or condition that would, in the opinion of the investigator and/or medical monitor, place the subject at an unacceptable risk to participate in this study. History of or suspected history of alcohol misuse or recreational substance abuse. Treatment with oral or IV corticosteroids within 8 weeks prior to screening. Concurrent enrolment in another clinical study. Receipt of any investigational drug therapy of use of any biologicals within 6 months prior to screening. Known history of allergy or reaction to any component of the investigational product.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI2338 10 MG<br>MEDI2338 (10 mg) administered as a single, fixed intravenous (IV) dose over a minimum of 60 minutes using an infusion pump | Biological: MEDI2338<br>* MEDI2338 single intravenous (IV) dose (lowest dose)<br>|
| Experimental: MEDI2338 30 MG<br>MEDI2338 (30 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump | Biological: MEDI2338<br>* MEDI2338 single IV dose (next highest dose)<br>|
| Experimental: MEDI2338 100 MG<br>MEDI2338 (100 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump | Biological: MEDI2338<br>* MEDI2338 single IV dose (next highest dose)<br>|
| Experimental: MEDI2338 300 MG<br>MEDI2338 (300 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump | Biological: MEDI2338<br>* MEDI2338 single IV dose (next highest dose)<br>|
| Experimental: MEDI2338 1000 MG<br>MEDI2338 (1000 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump | Biological: MEDI2338<br>* MEDI2338 single IV dose (highest dose)<br>|
| Placebo Comparator: Placebo<br>Placebo administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump | Other: Placebo<br>* Placebo single IV dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Number of participants experiencing adverse events (includes both adverse events and serious adverse events) | Days 1 - 92 | 
| Incidence of Serious Adverse Events | Number of participants experiencing serious adverse events | Days 1 - 92 | 
| Incidence of Clinically Significant Hematology Laboratory Results | Number of participants experiencing clinically significant hematology laboratory results. A clinically significant hematology laboratory result is defined as an abnormal hematology laboratory result that results in a treatment-emergent adverse event. | Days 1 - 92 | 
| Incidence of Clinically Significant Electrocardiogram Results | Number of participants experiencing clinically significant electrocardiogram results. A clinically significant electrocardiogram result is defined as an abnormal electrocardiogram result that results in a treatment-emergent adverse event. | Days 1 - 92 | 
| Incidence of Clinically Significant Vital Signs Results | Number of participants experiencing clinically significant vital signs results. A clinically significant vital signs result is defined as an abnormal vital signs result that results in a treatment-emergent adverse event. | Days 1 - 92 | 
| Incidence of Clinically Significant Serum Chemistry Laboratory Results | Number of participants experiencing clinically significant serum chemistry laboratory results. A clinically significant serum chemistry laboratory result is defined as an abnormal serum chemistry laboratory result that results in a treatment-emergent adverse event. | Days 1 - 92 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-Time Curve From Time Zero to Infinity | Area under the serum concentration-time curve from time zerio to infinity of MEDI2338 | Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92) | 
| Area Under the Serum Concentration-Time Profile From Time Zero to the Last Measurable Time Point | Area under the serum concentration-time profile from time zero to the last measurable time point of MEDI2338 | Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92) | 
| Incidence of Anti-drug Antibodies (ADA) to MEDI2338 | Number of participants with ADA to MEDI2338 | Days 1, 57, and 92 | 
| Observed Maximum Concentration (Cmax) | Cmax of MEDI2338 | Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92) | 
| Apparent Terminal Elimination Phase Half-life (t1/2) | t1/2 of MEDI2338 | Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92) | 
| Clearance (CL) | CL of MEDI2338 | Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD