Part I (SAD) - Healthy Participants Clinical Trial
Official title:
Safety, Tolerability, Pharmacokinetics and Immunogenicity of MEDI3506 Administered as Single Ascending Doses in Healthy Adult Subjects, as Multiple Ascending Doses in COPD Subjects and Single Dose in Healthy Japanese Subjects
| Verified date | September 2020 |
| Source | MedImmune LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a Phase 1, randomised, blinded, placebo controlled, study designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity response to single and multiple doses of MEDI3506.
| Status | Completed |
| Enrollment | 88 |
| Est. completion date | September 30, 2019 |
| Est. primary completion date | September 30, 2019 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility |
Inclusion Criteria Part 1 1. Healthy volunteers aged 18 through 55 years at the time of consent. 2. Non-smokers, healthy current smokers, and ex-smokers are permitted. 3. Pre-bronchodilator forced expiratory volume in 1 second (FEV1) >= 80% predicted (using the Global Lung Initiative [GLI] predicted values) at screening. 4. Body mass index (BMI) of 19.0 through 32.0 kg/m^2 at screening. 5. Current history of mild atopy. Inclusion Criteria Part 2 1. Aged 40 through 80 years at the time of screening. 2. BMI of 19.0 through 35.0 kg/m^2 at screening. 3. Participants must be current on pneumococcus and annual influenza vaccines. 4. Documented history of COPD with a post-bronchodilator FEV1/force vital capacity (FVC) <0.70 and a post-bronchodilator FEV1 =50% predicted at screening. 5. Clinically stable and free from an acute exacerbation of COPD for 8 weeks prior to Day 1. 6. Current or ex-smoker with a tobacco history of =10 pack-years. Inclusion Criteria Part 3 1. Japanese participants must have been born in Japan, have both parents and grandparents of Japanese origin, and not have lived outside of Japan for more than 5 years. 2. Healthy participants aged 20 through 55 years at the time of consent. 3. Non-smokers, healthy current smokers, and ex-smokers are permitted. 4. BMI of 18.0 through 32.0 kg/m^2 at screening. Exclusion Criteria Part 1 1. Concurrent enrollment in another clinical study involving a study treatment. 2. Received administration of study drug or participated in a device trial within 3 months, prior to screening (Visit 1). 3. Participant is a participating investigator, sub-investigator, study coordinator or employee of the participating site, or is a first-degree relative of the aforementioned. 4. Any active medical or psychiatric condition or other reason 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 investigational product or reduce the participant's ability to participate in the study. 5. Any clinically relevant abnormal findings on physical examination of the cardiovascular system including electrocardiogram (ECG) and vital signs at screening or randomization. 6. Abnormal vital signs, after 10 minutes supine rest. Exclusion Criteria Part 2 1. Concurrent enrolment in another clinical study involving investigational treatment. 2. Received administration of study drug or participated in a device trial within 3 months, prior to screening (Visit 1). 3. Participant is a participating investigator, sub-investigator, study coordinator, or employee of the participating site, or is a first-degree relative of the aforementioned. 4. Any active medical or psychiatric condition or other reason that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of participant's safety or study results. This includes, but is not limited to: - Uncontrolled diabetes - Hypertension during the screening period - Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure - Clinically significant Aortic stenosis - Pulmonary Arterial Hypertension Exclusion Criteria Part 3 1. Concurrent enrolment in another clinical study involving study treatment. 2. Received administration of study drug or participated in a device trial within 3 months, prior to screening (Visit 1). 3. Any active medical or psychiatric condition or other reason 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 product or reduce the participant's ability to participate in the study. 4. Any clinically relevant abnormal findings on physical examination of the cardiovascular system including ECG and vital signs at screening, and Day 1(pre-dose). 5. Any other clinically relevant abnormal findings on physical examination or laboratory testing including hematology, coagulation, clinical chemistry or urinalysis at screening or randomisation. |
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Manchester |
| Lead Sponsor | Collaborator |
|---|---|
| MedImmune LLC |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESI) in Part 1, Part 2, and Part 3 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. An adverse event of special interest (AESI) was defined as any serious or nonserious event of scientific and medical interest specific to understand the study drug. | From Day 1 through Day 169 | |
| Primary | Number of Participants With Grade 2 or More Toxicity Grades Reported in Laboratory Parameters at Day 169 for Part 1, Part 2, and Part 3 | Number of participants with Grade 2 or more toxicity grades reported in laboratory parameters are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology and serum chemistry. | Day 169 | |
| Primary | Changes From Baseline in Blood Pressure at Day 169 in Part 1, Part 2, and Part 3 | Change from baseline in blood pressure at Day 169 in Part 1, Part 2, and Part 3 are reported. | Day 169 | |
| Primary | Changes From Baseline in Pulse Rate at Day 169 in Part 1, Part 2, and Part 3 | Change from baseline in pulse rate at Day 169 in Part 1, Part 2, and Part 3 is reported. | Baseline (Day 1) and Day 169 | |
| Primary | Changes From Baseline in Respiratory Rate at Day 169 in Part 1, Part 2, and Part 3 | Change from baseline in respiratory rate at Day 169 in Part 1, Part 2, and Part 3 are reported. | Baseline (Day 1) and Day 169 | |
| Primary | Changes From Baseline in Body Temperature Rate at Day 169 in Part 1, Part 2, and Part 3 | Change from baseline in body temperature at Day 169 in Part 1, Part 2, and Part 3 are reported. | Baseline (Day 1) and Day 169 | |
| Primary | Number of Participants With Change From Baseline in QTcF in Part 1, Part 2, and Part 3 | Number of participants with change from basleine in QTcF in Part 1, Part 2, and Part 3 are reported. The change from baseline in QTcF at Day 169 data are reported in 3 categories as: <= 30 msec, > 30 to <= 60 msec, and > 60 msec. | Baseline (Day 1) and Day 169 | |
| Secondary | Maximum Observed Concentration (Cmax) of MEDI3506 After Single Dose for Part 1 and Part 3 | The Cmax of MEDI3506 after single dose for Part 1 and Part 3 are reported. | Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Time to Maximum Concentration (Tmax) of MEDI3506 After Single Dose for Part 1 and Part 3 | The Tmax of MEDI3506 after single dose for Part 1 and Part 3 is reported. | Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3506 After Single Dose for Part 1 and Part 3 | The AUC0-inf of MEDI3506 after single dose for Part 1 and Part 3 are reported. | Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Terminal Elimination Half-life (t1/2) of MEDI3506 After Single Dose for Part 1 and Part 3 | The t1/2 of MEDI3506 after single dose for Part 1 and Part 3 are reported. | Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Apparent Clearance (CL/F) of MEDI3506 From Body After Single Dose for Part 1 and Part 3 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Total clearance from the body (CL) from Part 1 and Part 3 after intravenous administration or apparent systemic clearance (CL/F) after subcutaneous administration in Part 1 of the study are reported. | Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Trough Serum Concentration (Ctrough) of MEDI3506 After 1st Dose in Part 2 | Lowest serum concentration of MEDI3506 observed within the dosing interval after 1st dose in Part 2 is reported. | Day 1 (predose), Day 3, Day 8, Day 15 (predose) | |
| Secondary | Trough Serum Concentration (Ctrough) of MEDI3506 After 3rd Dose in Part 2 | Lowest serum concentration of MEDI3506 observed within the dosing interval after 3rd dose in Part 2 is reported. | Day 29 (predose), Day 36, and Day 43 | |
| Secondary | Terminal Elimination Half-life (t1/2) of MEDI3506 in Part 2 | The t1/2 of MEDI3506 after 3rd dose in Part 2 is reported. | Day 36, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169 | |
| Secondary | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3506 treatment in Part 1, Part 2, and Part 3 | Number of participants with positive ADA to MEDI3506 treatment after single administration of MEDI3506 (Part 1 and Part 3) and after multiple dose administration of MEDI3506 (Part 2) at any time point during the study are reported. | Part 1 and Part 3: Day 1 (predose), Day 29, Day 57, Day 85, Day 113, Day 141, and Day 169; Part 2: Day 1 (predose), Day 29, Day 85, and Day 169 |