Safety and Tolerability of MEDI9314 as Single Ascending Dose in Healthy Subjects

A Phase 1a Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI9314 in Healthy Adult Subjects

This is a phase 1a randomized, blinded, placebo-controlled, single-ascending dose study to assess the safety and tolerability of MEDI9314 in healthy adult subjects

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Safety
• Intervention / Treatment: Drug: MEDI9314; Drug: placebo

Detailed Description

This is a phase I study to assess the safety, tolerability pharmacokinetics, and immunogenicity of MEDI9314 following single dose administration to healthy subjects

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent.
2. Age 18 through 50 years at the time of screening.
3. Female subjects must be of non-childbearing potential.
4. Nonsterilized males who are sexually active with a female partner of childbearing potential must use condom and spermicide.
5. Body mass index of 19.0 through 32.0 kg/m2 at screening.
6. No clinically significant abnormality on the basis of medical/medication history or physical examination.
7. Negative drugs of abuse (DOA).
8. Able and willing to comply with the requirements of the protocol and complete the study until the end of the safety follow up period.
9. For the Japanese Cohort, both of the subject's parents and both sets of grandparents must be Japanese.

Exclusion Criteria:

1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
2. Concurrent enrollment in another clinical study involving any treatment.
3. Individuals who are legally institutionalized.
4. Receipt of > 2 marketed or investigational biologic agents.
5. Receipt of an investigational biologic agent within 4 months or 5 half-lives prior to screening, whichever is longer.
6. Receipt of any investigational non biologic agent within 3 months or 5 half lives prior to screening, whichever is longer.
7. Use of any medication (prescription or over the counter, including herbal remedies) within 14 days or 5 half lives of Day 1, whichever is longer, unless in the opinion of the investigator and medical monitor the medication will not interfere with the study procedures or compromise subject safety.
8. Known history of allergy or reaction to any component of the investigational product formulation.
9. History of anaphylaxis following any biologic therapy.
10. Any clinically relevant abnormal findings in physical examination ECG, vital signs, and laboratory parameters.
11. Positive tuberculosis (TB) test (QuantiFERON®-TB Gold In-tube).
12. Positive hepatitis B surface antigen, hepatitis C virus antibody or HIV test at screening.
13. Receipt of live attenuated vaccines 30 days prior to the date of screening.
14. Where donation of blood or blood products was in excess of 500 mL within an 8-week period in the 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo
Experimental: Cohort 2; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo
Experimental: Cohort 3; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo
Experimental: Cohort 4; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo
Experimental: Japanese Cohort; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo
Experimental: Cohort 5; single dose of MEDI9314 or placebo	Drug: MEDI9314; single dose of MEDI9314; Drug: placebo; single dose of placebo

What is the study measuring?

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 is any unfavourable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with use of medicinal product, whether or not considered related to medicinal product. Serious adverse event is any AE that resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. 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 and up to Day 240.	From the start of study drug administration upto Day 240
Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs	TEAEs observed in participants with clinically significant ECG abnormalities were reported.	From the start of study drug administration upto Day 240
Number of Participants With Vital Signs Abnormalities Reported as TEAEs	Vital sign parameters included blood pressure, heart rate, and temperature. TEAEs observed in participants with clinically significant vital signs abnormalities were reported.	From the start of study drug administration upto Day 240
Number of Participants With Physical Examination Abnormalities Reported as TEAEs	Adverse events observed in participants with clinically significant physical abnormalities were assessed.	From the start of study drug administration upto Day 240
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs	An abnormal laboratory finding which required an action or medical intervention by the investigator, or a finding judged by the investigator as medically significant should be reported as an adverse event. Laboratory evaluation (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.	From the start of study drug administration upto Day 240
Number of Participants With TEAEs Related to Injection Site Reactions	Adverse events of special interest observed in participants with clinically significant injection site reaction were assessed.	From the start of study drug administration upto Day 240

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314	The area under the serum drug concentration versus time curves from zero to infinity of MEDI9314.	Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast)	The area under the serum drug concentration versus time curve, to last quantifiable time point of MEDI9314.	Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314	The maximum observed serum drug concentration of MEDI9314.	Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314	The time to maximum observed serum drug concentration of MEDI9314.	Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Terminal Phase Elimination Half-life (t1/2) of MEDI9314	Terminal phase elimination half-life of MEDI9314	Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Serum Concentrations of MEDI9314	Baseline indicates the last assessment prior to first dose. For this study, the lower limit of quantification (LLOQ) for MEDI9314 serum concentrations were 19.53 μg/mL. Where serum concentrations were below this value, a serum concentration of 9.770 μg/mL was imputed.	Baseline (Day 1 [predose]) and Day 240
Number of Participants Positive for Anti-Drug Antibodies to MEDI9314	Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9314. The number of participants with positive serum antibodies to MEDI9314 were presented.	Baseline (Day 1 [predose]) and Day 240

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Principal Investigator: Muna Albayaty, MBChB, FFPM, Parexel; Principal Investigator: Hakop Gevorkyan, MD, Parexel

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2016
• Primary Completion (Actual): November 17, 2016
• Study Completion (Actual): June 12, 2017

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimate): February 1, 2016

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Immunogenicity; Tolerability; MEDI9314
• Other Study ID Numbers: D4361C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES