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

Phase 1

Completed

• Conditions: Part I (SAD) - Healthy Participants; Part III (J-SD) - Healthy Japanese Participants; Part II (MAD) - Chronic Obstructive Pulmonary Disease
• Interventions: Drug: MEDI3506; Drug: Placebo

• Registration Number: NCT03096795
• Lead Sponsor: MedImmune LLC

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

Study Timeline

• Study First Submitted: 2017-03-01
• Study First Submitted QC: 2017-03-24
• Study First Posted: 2017-03-30
• Study Start: 2017-05-15
• Primary Completion: 2019-09-30
• Study Completion: 2019-09-30
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-30
• Last Update Posted: 2020-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: MEDI3506 SC Dose 3	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 3 subcutaneously.
Part 1: MEDI3506 SC Dose 4	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 4 subcutaneously.
Part 2: MEDI3506 SC Dose 5	MEDI3506	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).
Part 1: Placebo	MEDI3506	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.
Part 1: MEDI3506 SC Dose 2	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 2 subcutaneously.
Part 1: MEDI3506 IV Dose 6	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 intravenously.
Part 2: Placebo	Placebo	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).
Part 2: MEDI3506 SC Dose 4	MEDI3506	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).
Part 1: Placebo	Placebo	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.
Part 2: Placebo	MEDI3506	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).
Part 1: MEDI3506 SC Dose 5	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 5 subcutaneously.
Part 1: MEDI3506 SC Dose 6	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 subcutaneously.
Part 1: MEDI3506 SC Dose 1	MEDI3506	Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 1 subcutaneously.
Part 2: MEDI3506 SC Dose 6	MEDI3506	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).
Part 3: Placebo	MEDI3506	Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously.
Part 3: Placebo	Placebo	Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously.
Part 3: MEDI3506 IV Dose 6	MEDI3506	Healthy Japanese participants will receive a single MEDI3506 Dose 6 intravenously.

Primary Outcome Measures

Name	Time	Method
Changes From Baseline in Blood Pressure at Day 169 in Part 1, Part 2, and Part 3	Day 169	Change from baseline in blood pressure at Day 169 in Part 1, Part 2, and Part 3 are reported.
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	From Day 1 through Day 169	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.
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	Day 169	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.
Changes From Baseline in Pulse Rate at Day 169 in Part 1, Part 2, and Part 3	Baseline (Day 1) and Day 169	Change from baseline in pulse rate at Day 169 in Part 1, Part 2, and Part 3 is reported.
Changes From Baseline in Respiratory Rate at Day 169 in Part 1, Part 2, and Part 3	Baseline (Day 1) and Day 169	Change from baseline in respiratory rate at Day 169 in Part 1, Part 2, and Part 3 are reported.
Changes From Baseline in Body Temperature Rate at Day 169 in Part 1, Part 2, and Part 3	Baseline (Day 1) and Day 169	Change from baseline in body temperature at Day 169 in Part 1, Part 2, and Part 3 are reported.
Number of Participants With Change From Baseline in QTcF in Part 1, Part 2, and Part 3	Baseline (Day 1) and Day 169	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.

Secondary Outcome Measures

Name	Time	Method
Terminal Elimination Half-life (t1/2) of MEDI3506 in Part 2	Day 36, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169	The t1/2 of MEDI3506 after 3rd dose in Part 2 is reported.
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	The AUC0-inf of MEDI3506 after single dose for Part 1 and Part 3 are reported.
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3506 treatment in Part 1, Part 2, and Part 3	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	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.
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	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.
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	The Cmax of MEDI3506 after single dose for Part 1 and Part 3 are reported.
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	The Tmax of MEDI3506 after single dose for Part 1 and Part 3 is reported.
Trough Serum Concentration (Ctrough) of MEDI3506 After 1st Dose in Part 2	Day 1 (predose), Day 3, Day 8, Day 15 (predose)	Lowest serum concentration of MEDI3506 observed within the dosing interval after 1st dose in Part 2 is reported.
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	The t1/2 of MEDI3506 after single dose for Part 1 and Part 3 are reported.
Trough Serum Concentration (Ctrough) of MEDI3506 After 3rd Dose in Part 2	Day 29 (predose), Day 36, and Day 43	Lowest serum concentration of MEDI3506 observed within the dosing interval after 3rd dose in Part 2 is reported.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom