Safety and Tolerability of MEDI3506 in Healthy Participants, in Participants With COPD and Healthy Japanese Participants

MedImmune

Status and phase: Completed; Phase 1

Conditions: Part I (SAD) - Healthy Participants; Part III (J-SD) - Healthy Japanese Participants; Part II (MAD) - Chronic Obstructive Pulmonary Disease

Treatments: Drug: MEDI3506; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03096795

D9180C00001

Details and patient eligibility

About

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.

Full description

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 administered by either subcutaneous (SC) or intravenous (IV) routes.

Part I: Single Ascending Doses in Healthy Participants with a History of Mild Atopy

Part II: Multiple Ascending Doses in Participants with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II Chronic Obstructive Pulmonary Disease (COPD)

Part III: Single Dose in Healthy Japanese Participants

Enrollment: 88 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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88 participants in 14 patient groups, including a placebo group

Part 1: Placebo

Placebo Comparator group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to house dust mite (HDM) will receive a single dose of placebo matched to MEDI3506 subcutaneously or intravenously.

Treatment:

Drug: MEDI3506

Drug: Placebo

Part 1: MEDI3506 SC Dose 1

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 1 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 2

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 2 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 3

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 3 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 4

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 4 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 5

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 5 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 6

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 subcutaneously.

Treatment:

Drug: MEDI3506

Part 1: MEDI3506 IV Dose 6

Experimental group

Description:

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 intravenously.

Treatment:

Drug: MEDI3506

Part 2: Placebo

Placebo Comparator group

Description:

Participants with COPD will receive 3 administration of placebo matched to MEDI3506 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).

Treatment:

Drug: MEDI3506

Drug: Placebo

Part 2: MEDI3506 SC Dose 4

Experimental group

Description:

Participants with COPD will receive 3 administration of MEDI3506 Dose 4 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).

Treatment:

Drug: MEDI3506

Part 2: MEDI3506 SC Dose 5

Experimental group

Description:

Participants with COPD will receive 3 administration of MEDI3506 Dose 5 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).

Treatment:

Drug: MEDI3506

Part 2: MEDI3506 SC Dose 6

Experimental group

Description:

Participants with COPD will receive 3 administration of MEDI3506 Dose 6 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).

Treatment:

Drug: MEDI3506

Part 3: Placebo

Placebo Comparator group

Description:

Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously.

Treatment:

Drug: MEDI3506

Drug: Placebo

Part 3: MEDI3506 IV Dose 6

Experimental group

Description:

Healthy Japanese participants will receive a single MEDI3506 Dose 6 intravenously.

Treatment:

Drug: MEDI3506