Clinical trial NCT03096795: Safety and Tolerability of MEDI3506 in Healthy Participants, in Participants With COPD and Healthy Japanese Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Part I (SAD) - Healthy Participants
Part II (MAD) - Chronic Obstructive Pulmonary Disease
Part III (J-SD) - Healthy Japanese Participants
Keywords: MEDI3506
Safety
Tolerability
Pharmacokinetics
Immunogenicity
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-03-30
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: From Day 1 through Day 169
measure: 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
timeFrame: Day 169
measure: Changes From Baseline in Blood Pressure at Day 169 in Part 1, Part 2, and Part 3
timeFrame: Day 169
measure: Changes From Baseline in Pulse Rate at Day 169 in Part 1, Part 2, and Part 3
timeFrame: Baseline (Day 1) and Day 169
measure: Changes From Baseline in Respiratory Rate at Day 169 in Part 1, Part 2, and Part 3
timeFrame: Baseline (Day 1) and Day 169
measure: Changes From Baseline in Body Temperature Rate at Day 169 in Part 1, Part 2, and Part 3
timeFrame: Baseline (Day 1) and Day 169
measure: Number of Participants With Change From Baseline in QTcF in Part 1, Part 2, and Part 3
timeFrame: Baseline (Day 1) and Day 169
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of MEDI3506 After Single Dose for Part 1 and Part 3
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of MEDI3506 After Single Dose for Part 1 and Part 3
timeFrame: 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
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3506 After Single Dose for Part 1 and Part 3
timeFrame: 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
measure: Terminal Elimination Half-life (t1/2) of MEDI3506 After Single Dose for Part 1 and Part 3
timeFrame: 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
measure: Apparent Clearance (CL/F) of MEDI3506 From Body After Single Dose for Part 1 and Part 3
timeFrame: 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
measure: Trough Serum Concentration (Ctrough) of MEDI3506 After 1st Dose in Part 2
timeFrame: Day 1 (predose), Day 3, Day 8, Day 15 (predose)
measure: Trough Serum Concentration (Ctrough) of MEDI3506 After 3rd Dose in Part 2
timeFrame: Day 29 (predose), Day 36, and Day 43
measure: Terminal Elimination Half-life (t1/2) of MEDI3506 in Part 2
timeFrame: Day 36, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3506 treatment in Part 1, Part 2, and Part 3
timeFrame: 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
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Parexel
name: Muna Albayaty, MBChB, FFPM. MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Medicines Evaluation Unit
name: David Singh, MD
role: PRINCIPAL_INVESTIGATOR
References: