Study to Evaluate the Safety, Tolerability,Immunogenicity, and Pharmacokinetics of MEDI-528 in Healthy Adult Volunteers

A Phase I, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability,Immunogenicity, and Pharmacokinetics of MEDI-528, a Humanized Monoclonal Anti-Interleukin-9 Antibody, in Healthy Adult Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00192296

Enrollment

Registered

2005-09-19

Start date

2004-08-31

Completion date

2005-03-31

Last updated

2014-03-06

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

Conditions

Asthma

Brief summary

Phase I study to evaluate the safety and tolerability of escalating single IV doses of MEDI-528.

Detailed description

The primary objective of this Phase I study is to evaluate the safety and tolerability of escalating single IV doses of MEDI-528 administered to healthy adult volunteers.

Interventions

BIOLOGICALMEDI-528 0.3 mg/kg

MEDI-528 (0.3 mg/kg) administered as a single, intravenous (IV) dose

BIOLOGICALMEDI-528 1 mg/kg

MEDI-528 (1 mg/kg) administered as a single, IV dose

BIOLOGICALMEDI-528 3 mg/kg

MEDI-528 (3 mg/kg) administered as a single, IV dose

BIOLOGICALMEDI-528 9 mg/kg

MEDI-528 (9 mg/kg) administered as a single, IV dose

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 49 Years

Healthy volunteers

Yes

Inclusion criteria

* Males and females age 18 up to and including 49 years of age at the time of the first dose of study drug * Weight \< 89 kg * Written informed consent obtained from the volunteer * Healthy by medical history and physical examination * Sexually active females, unless surgically sterile or at least one year post-menopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap,abstinence, use of a condom by the sexual partner or sterile sexual partner) for 3 months before the first dose of study drug, and must agree to continue using such precautions through 84 days after their dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions through 84 days after their dose of study drug. * Use of common over-the-counter medications such as topical corticosteroids, decongestants, antihistamines, analgesics, and antacids is permitted unless, in the opinion of the investigator, it would interfere with either the volunteer's ability to complete the study or interpretation of study results. * Ability to complete the follow-up period of 84 days * Willing to forego other forms of experimental treatment during the study period of 84 days

Exclusion criteria

* Acute illnesses or evidence of significant active infection, such as fever ≥38.0°C (100.5°F) at the start of the study * Use of prescription medications, other than contraceptives, in the 28-day period before Study Day 0 * Blood donation in excess of 400 mL within 6 months of the time of entry into the study * History of use of tobacco products within 3 years of Study Day 0 or history of smoking of \>10 pack-years * History of immunodeficiency or receipt or current use of immunosuppressive drugs including systemic corticosteroids * History of allergic disease or reactions likely to be exacerbated by any component of the Study Drug (described in the Investigator's Brochure) * History of substance abuse that, in the opinion of the investigator, may compromise the ability of the study subject to complete the study and follow-up period * Evidence of any systemic disease on physical examination * Evidence of infection with hepatitis A, B, or C virus or HIV-1 * Receipt of immunoglobulins or blood products within 60 days of entering the study * Receipt of any investigational drug therapy within 60 days of the first dose of study drug through Study Day 84 (use of licensed agents for indications not listed in the package insert is permitted) * Any of the following: CBC: Hgb \< 12.0 gm/dL; WBC \< 4,000/mm3; platelet count \<125,000/mm3 (or laboratory normal values); Na, K, Cl, CO2, AST, ALT, BUN, 4-hour fasting glucose, amylase, lipase, creatinine, troponin \> upper limit of normal; other abnormal laboratory values in the screening panel which in the opinion of the principal investigator are judged to be clinically significant. * Clinically significant abnormality, as determined by the investigator, on 12-lead electrocardiogram at the time of initial screening * Elective surgery planned during the study period through Study Day 84 * Pregnancy (sexually active females must have a negative serum pregnancy test on the day of the first dose of the study drug, before dosing) * Nursing mother * The presence of any acute or chronic organ-specific condition or any concern, which in the opinion of the investigator, may interfere with the conduct or interpretation of the study

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Adverse Events	Days 0 - 84	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Incidence of Abnormal Troponin Levels	Days 0, 7, 14, 21, and 28	Number of participants with troponin levels greater than upper limit of normal (\> 0.05 ng/mL)
Incidence of Serious Adverse Events	Days 0 - 84	Number of participants experiencing serious adverse events

Secondary

Measure	Time frame	Description
Observed Maximum Serum Concentration (Cmax)	Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	Cmax of MEDI-528
Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)]	Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(0-t) of MEDI-528
Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)]	Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(0-infinity) of MEDI-528
Terminal Phase Elimination Rate (Vz)	Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	Vz of MEDI-528
Total Body Clearance (CL)	Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	CL of MEDI-528
Half-life (T1/2)	Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	T1/2 of MEDI-528
Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)]	Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(ext) of MEDI-528
Incidence of Anti-drug Antibodies (ADA) to MEDI-528	Days 14, 28, 42, and 84	Number of participants who had ADA detected at each time point
Time to Observed Maximum Serum Concentration (Tmax)	Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84	Tmax of MEDI-528

Countries

United States

Participant flow

Recruitment details

A total of 24 participants provided written informed consent and participated in the study between 13Aug2004 and 12Nov2004 at one site in New Orleans, Louisiana.

Pre-assignment details

Eligible participants received MEDI-528 in an open-label manner.

Participants by arm

Arm	Count
MEDI-528 0.3 mg	6
MEDI-528 1 mg	6
MEDI-528 3 mg	6
MEDI-528 9 mg	6
Total	24

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Withdrawal by Subject	0	1	0	0

Baseline characteristics

Characteristic	MEDI-528 0.3 mg	MEDI-528 1 mg	MEDI-528 3 mg	MEDI-528 9 mg	Total
Age, Continuous	25.8 Years STANDARD_DEVIATION 11.1	29.8 Years STANDARD_DEVIATION 8.4	25.5 Years STANDARD_DEVIATION 8.8	30.5 Years STANDARD_DEVIATION 8.2	27.9 Years STANDARD_DEVIATION 8.9
Sex: Female, Male Female	0 Participants	5 Participants	4 Participants	4 Participants	13 Participants
Sex: Female, Male Male	6 Participants	1 Participants	2 Participants	2 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 6	4 / 6	6 / 6	2 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6

Outcome results

Primary