Phase 1 Randomized Double-blind Placebo Controlled Study to Evaluate Safety and PK of MEDI3902 in Healthy Adults

A Phase 1 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of MEDI3902 in Healthy Adults

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02255760

Enrollment

Registered

2014-10-03

Start date

2014-09-04

Completion date

2015-04-20

Last updated

2018-08-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MEDI3902 for Prevention of P. Aeruginosa Pneumonia

Keywords

MEDI3902, Safety,, Pharmacokinetics,, Healthy Volunteers

Brief summary

Detailed description

This is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation study evaluating the safety and tolerability of a single ascending IV dose of MEDI3902 in healthy adult subjects 18 to 60 years of age. Approximately 40 subjects will be enrolled across 4 fixed dose cohorts at 1 study site. This study will last approximately 90 days, constituting a screening period of up to 28 days, 1 day of investigational product administration, and a 60 day safety follow up period.

Interventions

DRUGMEDI3902 - Dose 1

Participants will receive a single IV dose of MEDI3902 infused for a minimum of 13 minutes on Day 1.

DRUGMEDI3902 - Dose 2

Participants will receive a single IV dose of MEDI3902 infused for a minimum of 38 minutes on Day 1.

DRUGMEDI3902 - Dose 3

Participants will receive a single IV dose of MEDI3902 infused for a minimum of 75 minutes on Day 1.

DRUGMEDI3902 - Dose 4

Participants will received a single IV dose of MEDI3902 infused for a minimum of 150 minutes on Day 1.

OTHERPlacebo

Participants will receive a single dose of placebo by IV infusion up to a maximum of 12 hours.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

1. Age 18 through 60 years at the time of screening 2. Written informed consent 3. Weight greater than or equal to (\>=) 45 kilogram (kg) and less than or equal to (\<=) 110 kg at screening 4. Healthy by medical history, physical examination, and baseline safety laboratory studies 5. Systolic blood pressure (BP) less than (\<) 140 millimeter of mercury (mmHg) and diastolic BP \< 90 mmHg at screening 6. Electrocardiogram (ECG) without clinically significant abnormalities at screening 7. Able to complete the follow-up period through Day 61 as required by the protocol. 8. Females of childbearing potential who are sexually active with a nonsterilized male partner must have used a highly effective method of contraception for at least 28 days prior to dosing with investigational product and must agree to continue using such precautions through Day 61 of the study.

Exclusion criteria

1. Acute (time-limited) illness, including fever 99.5 degree Fahrenheit (0\^F), on day prior to or day of planned dosing 2. Any drug therapy within 7 days prior to Day 1 (except contraceptives or a single use of acetaminophen, aspirin, antihistamine, or combination over-the-counter (OTC) product that contains acetaminophen with an antihistamine, or OTC non-steroidal anti inflammatory agent at a dose equal to or lower than that recommended on the package). Vitamins and other nutritional supplements that are not newly introduced, ie, have been taken for at least 30 days prior to enrolment, are not exclusionary 3. Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 2 months prior to screening 4. Receipt of immunoglobulin or blood products within 6 months prior to screening 5. Receipt of any investigational product in the preceding 90 days or expected receipt of investigational product during the period of study follow-up, or concurrent participation in another interventional study Receipt of any vaccine within 7 days prior to investigational product dosing or planned receipt within 61 days after investigational product dosing except for influenza vaccine administered at least 28 days after dosing 6. Previous receipt of a mAb 7. Immunodeficiency due to illness, including human immunodeficiency virus (HIV) infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening. HIV testing must be negative at screening 8. History of allergic disease or reactions likely to be exacerbated by any component of the investigational product 9. Either history of active infection with hepatitis B or C 10. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or serum creatinine above the upper limit of normal (ULN) or hemoglobin, white blood cell count, or platelet count below the lower limit of normal at screening and in the predose blood sample 11. Pregnant or nursing mother 13\. History of alcohol or drug abuse within the past 2 years.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Day 1 to Day 29	An adverse event (AE) is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A TEAE is 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.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events of Special Interest (TEAESIs)	Day 1 to Day 61	An AE is any untoward medical occurrence attributed to study drug in a participant who received investigational product. TESAE was an event 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 that occurred after the initial receipt of the study drug. An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. TEAESIs were collected from the time of dosing through Day 61 after the last dose of study drug and included anaphylaxis, other serious allergic reactions, infusion-related reactions, hepatic function abnormalities and immune complex disease.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)	Day 1 to Day 29	Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: Hematology, serum chemistry, liver function, serum electrolytes and urinalysis.
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)	Day 1 to Day 7	Vital signs measurements included temperature, blood pressure (systolic and diastolic), pulse rate and respiratory rate.

Secondary

Measure	Time frame	Description
MEDI3902 Serum Clearance (CL) of MEDI3902	Pre-dose (24 hours prior to dose); at the end of the infusion, and 8 hours post infusion, and Days 2, 3, 7, 15, 22, 29, 43, and 61 post-dose	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The PK parameter CL was estimated based on the serum concentrations of MEDI3902. Non-compartmental PK data analysis was performed to estimate the serum PK parameters of MEDI3902.
Area Under the Serum Concentration-time Curve From Zero to Infinity (AUC [0-infinity])	Pre-dose (24 hours prior to dose); at the end of the infusion, and 8 hours post infusion, and Days 2, 3, 7, 15, 22, 29, 43, and 61 post-dose	Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). The PK parameter AUC (0-inf) was estimated based on the serum concentrations of MEDI3902. Non-compartmental PK data analysis was performed to estimate the serum PK parameters of MEDI3902.
Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI3902	Days 1 (pre-dose), 15, 29, and 61	Blood samples were collected to evaluate the antidrug antibody responses to MEDI3902 in serum. The number of participants positive for serum antibodies to MEDI3902 were presented.
Maximum Observed Serum Concentration (Cmax) for MEDI3902 After First Dose	Pre-dose (24 hours prior to dose); at the end of the infusion, and 8 hours post infusion, and Days 2, 3, 7, 15, 22, 29, 43, and 61 post-dose	The PK parameter Cmax was estimated based on the serum concentrations of MEDI3902. Non-compartmental PK data analysis was performed to estimate the serum PK parameters of MEDI3902.
Terminal Phase Elimination Half-life (t1/2)	Pre-dose (24 hours prior to dose); at the end of the infusion, and 8 hours post infusion, and Days 2, 3, 7, 15, 22, 29, 43, and 61 post-dose	The t1/2 is the time measured for the serum drug concentration of MEDI3902 to decrease by one half. The PK parameter t1/2 was estimated based on the serum concentrations of MEDI3902. Non-compartmental PK data analysis was performed to estimate the serum PK parameters of MEDI3902.
Volume of Distribution at Steady State (Vss)	Pre-dose (24 hours prior to dose); at the end of the infusion, and 8 hours post infusion, and Days 2, 3, 7, 15, 22, 29, 43, and 61 post-dose	Volume of distribution is defined as the theoretical volume in which the total amount of drug uniformly distributed to produce the desired serum concentration of a drug. The PK parameter Vss was estimated based on the serum concentrations of MEDI3902. Non-compartmental PK data analysis was performed to estimate the serum PK parameters of MEDI3902.

Countries

United States

Participant flow

Pre-assignment details

A total of 131 participants were screened, of which 75 did not meet eligibility criteria and were considered as screen failures; and the remaining 56 participants were randomized into the study.

Participants by arm

Arm	Count
Placebo Participants received a single dose of placebo by IV infusion up to a maximum of 12 hours.	14
MEDI3902 - Dose 1 Participants received a single IV dose of MEDI3902 infused for a minimum of 13 minutes on Day 1.	3
MEDI3902 - Dose 2 Participants received a single IV dose of MEDI3902 infused for a minimum of 38 minutes on Day 1.	15
MEDI3902 - Dose 3 Participants received a single IV dose of MEDI3902 infused for a minimum of 75 minutes on Day 1.	15
MEDI3902 - Dose 4 Participants received a single IV dose of MEDI3902 infused for a minimum of 150 minutes on Day 1.	9
Total	56

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Lost to Follow-up	0	1	0	0	0

Baseline characteristics

Characteristic	Placebo	MEDI3902 - Dose 1	MEDI3902 - Dose 2	MEDI3902 - Dose 3	MEDI3902 - Dose 4	Total
Age, Continuous	41.2 Years STANDARD_DEVIATION 10.9	34.0 Years STANDARD_DEVIATION 9.5	40.9 Years STANDARD_DEVIATION 11.8	40.3 Years STANDARD_DEVIATION 12.4	39.8 Years STANDARD_DEVIATION 13.1	40.3 Years STANDARD_DEVIATION 11.6
Sex: Female, Male Female	9 Participants	3 Participants	9 Participants	9 Participants	6 Participants	36 Participants
Sex: Female, Male Male	5 Participants	0 Participants	6 Participants	6 Participants	3 Participants	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 14	0 / 3	0 / 15	0 / 15	0 / 9
other Total, other adverse events	4 / 14	2 / 3	6 / 15	8 / 15	6 / 9
serious Total, serious adverse events	0 / 14	0 / 3	0 / 15	0 / 15	0 / 9

Outcome results

Primary

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: Hematology, serum chemistry, liver function, serum electrolytes and urinalysis.

Time frame: Day 1 to Day 29