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

NCT03096795 | Completed Phase 1

• 1 other identifier: D9180C00001
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (9)

• Maximum Observed Concentration (Cmax) of MEDI3506 After Single Dose for Part 1 and Part 3

  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

• Time to Maximum Concentration (Tmax) of MEDI3506 After Single Dose for Part 1 and Part 3

  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

• Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3506 After Single Dose for Part 1 and Part 3

  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

• Terminal Elimination Half-life (t1/2) of MEDI3506 After Single Dose for Part 1 and Part 3

  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

• Apparent Clearance (CL/F) of MEDI3506 From Body After Single Dose for Part 1 and Part 3

  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

Study Arms (14)

Part 1: Placebo

PLACEBO COMPARATOR

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.

Drug: MEDI3506; Drug: Placebo

Part 1: MEDI3506 SC Dose 1

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 2

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 3

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 4

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 5

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 SC Dose 6

EXPERIMENTAL

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

Drug: MEDI3506

Part 1: MEDI3506 IV Dose 6

EXPERIMENTAL

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

Drug: MEDI3506

Part 2: Placebo

PLACEBO COMPARATOR

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).

Drug: MEDI3506; Drug: Placebo

Part 2: MEDI3506 SC Dose 4

EXPERIMENTAL

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).

Drug: MEDI3506

Part 2: MEDI3506 SC Dose 5

EXPERIMENTAL

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).

Drug: MEDI3506

Part 2: MEDI3506 SC Dose 6

EXPERIMENTAL

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).

Drug: MEDI3506

Part 3: Placebo

PLACEBO COMPARATOR

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

Drug: MEDI3506; Drug: Placebo

Part 3: MEDI3506 IV Dose 6

EXPERIMENTAL

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

Drug: MEDI3506

Interventions

MEDI3506 DRUG

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 1 or Dose 2 or Dose 3 or Dose 4 or Dose 5 or Dose 6 subcutaneously and Dose 6 intravenously in Part 1. Participants with COPD will receive 3 administration of MEDI3506 Dose 4 or Dose 5 or Dose 6 subcutaneously two weeks apart over a 4-week dosing period in Part 2. Healthy Japanese participants will receive a single dose of MEDI3506 Dose 6 intravenously in Part 3.

Part 1: MEDI3506 IV Dose 6; Part 1: MEDI3506 SC Dose 1; Part 1: MEDI3506 SC Dose 2; Part 1: MEDI3506 SC Dose 3; Part 1: MEDI3506 SC Dose 4; Part 1: MEDI3506 SC Dose 5; Part 1: MEDI3506 SC Dose 6; Part 1: Placebo; Part 2: MEDI3506 SC Dose 4; Part 2: MEDI3506 SC Dose 5; Part 2: MEDI3506 SC Dose 6; Part 2: Placebo; Part 3: MEDI3506 IV Dose 6; Part 3: Placebo

Placebo DRUG

Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single dose of placebo matched to MEDI3506 subcutaneously or intravenously in Part 1. Participants with COPD will receive 3 administration of placebo matched to MEDI3506 subcutaneously two weeks apart over a 4-week dosing period in Part 2. Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously in Part 3.

Part 1: Placebo; Part 2: Placebo; Part 3: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers aged 18 through 55 years at the time of consent.
• Non-smokers, healthy current smokers, and ex-smokers are permitted.
• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) \>= 80% predicted (using the Global Lung Initiative \[GLI\] predicted values) at screening.
• Body mass index (BMI) of 19.0 through 32.0 kg/m\^2 at screening.
• Current history of mild atopy.
• Aged 40 through 80 years at the time of screening.
• BMI of 19.0 through 35.0 kg/m\^2 at screening.
• Participants must be current on pneumococcus and annual influenza vaccines.
• Documented history of COPD with a post-bronchodilator FEV1/force vital capacity (FVC) \<0.70 and a post-bronchodilator FEV1 ≥50% predicted at screening.
• Clinically stable and free from an acute exacerbation of COPD for 8 weeks prior to Day 1.
• Current or ex-smoker with a tobacco history of ≥10 pack-years.
• 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.
• Healthy participants aged 20 through 55 years at the time of consent.
• Non-smokers, healthy current smokers, and ex-smokers are permitted.
• BMI of 18.0 through 32.0 kg/m\^2 at screening.

You may not qualify if:

• Concurrent enrollment in another clinical study involving a study treatment.
• Received administration of study drug or participated in a device trial within 3 months, prior to screening (Visit 1).
• Participant is a participating investigator, sub-investigator, study coordinator or employee of the participating site, or is a first-degree relative of the aforementioned.
• 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.
• Any clinically relevant abnormal findings on physical examination of the cardiovascular system including electrocardiogram (ECG) and vital signs at screening or randomization.
• Abnormal vital signs, after 10 minutes supine rest.
• Concurrent enrolment in another clinical study involving investigational treatment.
• Received administration of study drug or participated in a device trial within 3 months, prior to screening (Visit 1).
• Participant is a participating investigator, sub-investigator, study coordinator, or employee of the participating site, or is a first-degree relative of the aforementioned.
• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (2)

Research Site

London, HA1 3UJ, United Kingdom

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

Related Links

• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Muna Albayaty, MBChB, FFPM. MSc

  Parexel

  PRINCIPAL INVESTIGATOR

• David Singh, MD

  Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 30, 2017
• Study Start: May 15, 2017
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: October 5, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (2)