Phase 1 Single-ascending Dose Study to Evaluate Safety and Tolerability of MEDI4920 in Healthy Adults

Study Overview
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Brief Summary
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Phase 1 single IV dose study to evaluate safety and tolerability of MEDI4920

Official Title
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A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Biological: MEDI4920 3 mg
* Biological: MEDI4920 10 mg
* Biological: MEDI4920 30 mg
* Biological: MEDI4920 100 mg
* Biological: MEDI4920 300 mg
* Biological: MEDI4920 1000 mg
* Biological: MEDI4920 3000 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as determined by a responsible study physician based on medical evaluation Body weight 40 to 100 kg Body mass index 19.0 to 30.0 kg/m2 Exclusion Criteria: History of allergy or sensitivity to Shellfish or protein based antigens previous immunization with KLH previous splenectomy History of diagnosed or suspected thromboembolic event or coagulation disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1. | Other: Placebo<br>* Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.<br>|
| Experimental: MEDI4920 3 mg<br>Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1. | Biological: MEDI4920 3 mg<br>* Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.<br>|
| Experimental: MEDI4920 10 mg<br>Participants received single IV dose of MEDI4920 10 mg infused on Day 1. | Biological: MEDI4920 10 mg<br>* Participants received single IV dose of MEDI4920 10 mg infused on Day 1.<br>|
| Experimental: MEDI4920 30 mg<br>Participants received single IV dose of MEDI4920 30 mg infused on Day 1. | Biological: MEDI4920 30 mg<br>* Participants received single IV dose of MEDI4920 30 mg infused on Day 1.<br>|
| Experimental: MEDI4920 100 mg<br>Participants received single IV dose of MEDI4920 100 mg infused on Day 1. | Biological: MEDI4920 100 mg<br>* Participants received single IV dose of MEDI4920 100 mg infused on Day 1.<br>|
| Experimental: MEDI4920 300 mg<br>Participants received single IV dose of MEDI4920 300 mg infused on Day 1. | Biological: MEDI4920 300 mg<br>* Participants received single IV dose of MEDI4920 300 mg infused on Day 1.<br>|
| Experimental: MEDI4920 1000 mg<br>Participants received single IV dose of MEDI4920 1000 mg infused on Day 1. | Biological: MEDI4920 1000 mg<br>* Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.<br>|
| Experimental: MEDI4920 3000 mg<br>Participants received single IV dose of MEDI4920 3000 mg infused on Day 1. | Biological: MEDI4920 3000 mg<br>* Participants received single IV dose of MEDI4920 3000 mg infused on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 situation (immediate risk of dying); persistent or significant disability or incapacity; congenital anomaly or birth defect in the offspring of a participant who received the study drug. A TEAE is defined as the event with onset after the start of infusion (Day 1) to Day 113 or early discontinuation visit inclusive. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0. | The start of study drug administration (Day 1) to the follow-up period (Day 113) or early discontinuation visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | The maximum observed plasma concentration (Cmax) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | The area under the plasma concentration-time curve from time zero to infinity (AUC 0-inf) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI4920 dose. The AUC (0-infinity)/D was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Terminal Elimination Half Life (t1/2) of MEDI4920 | The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Systemic Clearance (CL) of MEDI4920 | The systemic clearance (CL) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Volume of Distribution at Steady-state (Vss) of MEDI4920 | The volume of distribution at steady-state (Vss) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | The volume of distribution based on terminal phase (Vz) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | 
| Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Plasma samples were collected for assessment of anti-drug antibodies (ADA) against MEDI4920. The incidence of positive serum antibodies to MEDI4920 are presented. | Baseline (pre-infusion on Day 1) and post-baseline Days 15, 29, 57, and 113 or early discontinuation visit, whichever occurred first | 
| T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | The T-cell dependent antibody response (TDAR) assay measures the immune response (ie, antibody production) to an introduced antigen, keyhole limpet hemocyanin (KLH). The KLH is a potent immunostimulating protein with an extensive history of safe and effective use in vaccine development and immunological research. TDAR was evaluated by measuring anti-KLH IgG titers at a time point consistent with the expected timing for antibody responses following immunization. The primary time point for the analysis of the TDAR to KLH was Day 43. The data was presented for geometric mean ratio (MEDI4920/placebo) estimated from the dose response model. | Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Male, Healthy Female of non child bearing potential