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

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ClinicalTrials.gov Identifier: NCT02151110
Recruitment Status : Completed
First Posted : May 30, 2014
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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

Condition or disease Intervention/treatment Phase
Healthy Volunteer 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 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults
Actual Study Start Date : May 27, 2014
Actual Primary Completion Date : May 9, 2016
Actual Study Completion Date : May 9, 2016

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.
Other: Placebo
Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.

Experimental: MEDI4920 3 mg
Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.
Biological: MEDI4920 3 mg
Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.

Experimental: MEDI4920 10 mg
Participants received single IV dose of MEDI4920 10 mg infused on Day 1.
Biological: MEDI4920 10 mg
Participants received single IV dose of MEDI4920 10 mg infused on Day 1.

Experimental: MEDI4920 30 mg
Participants received single IV dose of MEDI4920 30 mg infused on Day 1.
Biological: MEDI4920 30 mg
Participants received single IV dose of MEDI4920 30 mg infused on Day 1.

Experimental: MEDI4920 100 mg
Participants received single IV dose of MEDI4920 100 mg infused on Day 1.
Biological: MEDI4920 100 mg
Participants received single IV dose of MEDI4920 100 mg infused on Day 1.

Experimental: MEDI4920 300 mg
Participants received single IV dose of MEDI4920 300 mg infused on Day 1.
Biological: MEDI4920 300 mg
Participants received single IV dose of MEDI4920 300 mg infused on Day 1.

Experimental: MEDI4920 1000 mg
Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.
Biological: MEDI4920 1000 mg
Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.

Experimental: MEDI4920 3000 mg
Participants received single IV dose of MEDI4920 3000 mg infused on Day 1.
Biological: MEDI4920 3000 mg
Participants received single IV dose of MEDI4920 3000 mg infused on Day 1.




Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: The start of study drug administration (Day 1) to the follow-up period (Day 113) or early discontinuation visit ]
    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.


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of MEDI4920 [ Time Frame: 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 ]
    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.

  2. Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 [ Time Frame: 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 ]
    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.

  3. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 [ Time Frame: 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 ]
    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.

  4. Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 [ Time Frame: 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 ]
    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.

  5. Terminal Elimination Half Life (t1/2) of MEDI4920 [ Time Frame: 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 ]
    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.

  6. Systemic Clearance (CL) of MEDI4920 [ Time Frame: 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 ]
    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.

  7. Volume of Distribution at Steady-state (Vss) of MEDI4920 [ Time Frame: 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 ]
    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.

  8. Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 [ Time Frame: 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 ]
    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.

  9. Percentage of Participants Positive for Anti-drug Antibodies (ADA) [ Time Frame: Baseline (pre-infusion on Day 1) and post-baseline Days 15, 29, 57, and 113 or early discontinuation visit, whichever occurred first ]
    Plasma samples were collected for assessment of anti-drug antibodies (ADA) against MEDI4920. The incidence of positive serum antibodies to MEDI4920 are presented.

  10. T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration [ Time Frame: Day 43 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02151110


Locations
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United Kingdom
Research Site
Leeds, United Kingdom, LS2 9LH
Sponsors and Collaborators
MedImmune LLC
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02151110    
Other Study ID Numbers: D5100C00001
First Posted: May 30, 2014    Key Record Dates
Results First Posted: February 15, 2019
Last Update Posted: February 15, 2019
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
Healthy Male
Healthy Female of non child bearing potential