A Study to Evaluate the Safety and Tolerability of the Administration of MEDI-528 When Administered in Multiple Doses to Adults With Mild Persistent Asthma

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled,Dose-Escalation Study to Evaluate the Safety and Tolerability of Multiple-Dose Subcutaneous Administration of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody,When Administered to Adults With Mild Persistent Asthma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00507130

Enrollment

Registered

2007-07-25

Start date

2007-07-31

Completion date

2008-09-30

Last updated

2013-12-11

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

Conditions

Asthma

Brief summary

The primary objective of this study is to evaluate the safety and tolerability of escalating multiple SC doses of MEDI-528 in adult patients with mild persistent asthma.

Detailed description

The secondary objectives of this study are to: 1. Assess the PK of MEDI-528; and 2. Assess the IM of MEDI-528 in this patient population.

Interventions

BIOLOGICALMEDI528 0.3 mg/kg

MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks

BIOLOGICALMEDI528 1 mg/kg

MEDI-528 at a dose of 1 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks

BIOLOGICALMEDI528 3 mg/kg

MEDI-528 at a dose of 3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks

OTHERPLACEBO

Placebo administered twice weekly as a subcutaneous (SC) dose for 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Male or female adults, age 18 through 65 years of age at time of screening; * Weight ≤ 100 kg and body mass index ≤ 35; * Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures; * Previously documented diagnosis of asthma based on episodic symptoms of airflow obstruction such as wheezing or chest tightness, with alternative diagnoses (e.g., chronic obstructive pulmonary disease) ruled out; * Currently receiving treatment with short-acting β2 agonists, ICS at doses ≤ 264 μg/day fluticasone or equivalent, or both (National Heart, Lung, and Blood Institute \[NHLBI\], 2002); * FEV1 or peak expiratory flow (PEF) ≥ 80% of predictable value; * Have had a diagnosis of mild persistent asthma, defined as having asthma symptoms with a frequency of more than twice a week but less than once daily, or nighttime symptoms with a frequency of more than twice a month but less than once a week (NHLBI, 2002); * Have AHR based on documented clinical history of either methacholine inhalation challenge with PC20 ≤ 16 mg/mL or partial reversibility of ≤ 12% in FEV1 within the past 18 months (including screening); * Able to provide spirometry readings that meet American Thoracic Society/European Respiratory Society standards (Miller, 2005); * Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including oral, implanted, or transdermal contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 21 days prior to the first dose of study drug, and must agree to continue using such precautions through Study Day 150. 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) and must agree to continue using such precautions through Study Day 150; * Ability to complete the study period, including follow-up period, of up to 150 days; and * Willing to forego other forms of experimental treatment and study procedures during the study.

Exclusion criteria

* Receipt of MEDI-528 in any previous clinical study or prior randomization into the trial; * History of allergy or reaction to any component of the MEDI-528 formulation; * Lung disease other than persistent asthma (e.g. chronic bronchitis); * FEV1 \< 80% of predicted values; * History of severe asthma or asthma exacerbation requiring intubation; * Use of systemic immunosuppressive drugs including systemic corticosteroids or ICS with doses \> 264 μg/day fluticasone or equivalent within 4 weeks prior to Study Day 0; * Use of long-acting β2 agonists, theophylline, cromolyn sodium, nedocromil sodium, leukotriene receptor antagonists, or any other inhaled or systemic medication for asthma (except short-acting β2 agonists or ICS at doses ≤ 264 μg/day fluticasone or equivalent) within the 2 weeks prior to Study Day 0; * Current use of any β-adrenergic antagonist (e.g., propranolol); * Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period; * Acute illnesses or evidence of significant active infection, such as fever ≥ 38.0°C (100.5°F) at screening and up through time of the first dose of study drug; * Current allergy vaccination therapy (desensitization immunotherapy), with less than 3 months of stable maintenance doses prior to screening; * Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to the first dose of study drug through Study Day 150; * Receipt of any therapy with a leukocyte-depleting agent unless recovery in white cell count has been documented before screening; * Pregnancy (sexually active females must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0); * Lactating or breastfeeding woman; * Evidence of infection with hepatitis B or C virus, or human immunodeficiency virus-1 or -2 (HIV-1 or HIV-2), or active infection with hepatitis A; * History of significant systemic disease (e.g., cancer, infection, hematological, renal, hepatic, coronary artery disease or other cardiovascular disease, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease); * History of cancer other than non-melanoma skin cancer or cervical carcinoma-in-situ treated with apparent success with curative therapy (remission for ≥ 1 year prior to screening); * History of primary immunodeficiency; * History of pancreatitis; * History of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to randomization or history of smoking of ≥ 10 pack-years; * Elective surgery planned during the study period through Study Day 150; * Clinically significant abnormalities on physical examination (other than asthma) prior to the first dose of study drug (including but not limited to splenomegaly); Clinically significant abnormality, as determined by the investigator, on 12-lead ECG, MRI, or chest radiograph at the time of screening; * At the time of screening, any abnormality of the following measurements: hemoglobin, total white blood cell count (WBC), platelet count, aspartate transaminase (AST), alanine transaminase (ALT), amylase, or serum creatinine above the upper limits of normal (ULN); or other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator, are judged to be clinically significant; * Evidence of any systemic disease or respiratory disease (other than asthma), any finding upon physical examination or history of any disease that, in the opinion of the investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or * Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Serious Adverse Events	Days 0 - 150	Number of participants experiencing serious adverse events
Incidence of Adverse Events	Days 0 - 150	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Incidence of Abnormal Troponin Levels	Days 0, 14, 28, 56, 84, and 150	Number of participants with troponin levels greater than upper limit of normal
Incidence of Abnormal Clinically Significant Electrocardiogram (ECG) Results	Days -14 to -1, 14, 28, 56, 84, and 150	Number of participants with abnormal clinically significant ECG results
Incidence of Abnormal Clinically Significant Magnetic Resonance Imaging (MRI) Results	Days -14 to -1 and 28	Number of participants experiencing abnormal clinically significant MRI results

Secondary

Measure	Time frame	Description
Observed Maximum Serum Concentration (Cmax)	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150	Cmax of MEDI-528
Terminal Phase Half-life (T1/2)	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150	T1/2 of MEDI-528
Incidence of Anti-drug Antibodies (ADA) to MEDI-528	Days 0, 28, 56, 84, 119, and 150	Number of participants with ADA to MEDI-528
Time to Observed Maximum Serum Concentration (Tmax)	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150	Tmax of MEDI-528

Countries

Canada, United States

Participant flow

Recruitment details

A total of 36 subjects were entered into the study between 28Jun2007 and 17Jul2008 at 8 sites in the United States of America (5 sites) and Canada (3 sites).

Pre-assignment details

Treatment assignments were determined using a block randomization procedure at a 3:1 active treatment-to-placebo ratio through an interactive voice response system (IVRS). When a subject was assigned a Participant Identification Number by the IVRS, the subject was considered randomized into the study.

Participants by arm

Arm	Count
PLACEBO Placebo administered twice weekly as a subcutaneous (SC) dose for 4 weeks	9
MEDI528 0.3 mg/kg MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a SC dose for 4 weeks	9
MEDI528 1 mg/kg MEDI-528 at a dose of 1 mg/kg administered twice weekly as a SC dose for 4 weeks	9
MEDI528 3 mg/kg MEDI-528 at a dose of 3 mg/kg administered twice weekly as a SC dose for 4 weeks	9
Total	36

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Lost to Follow-up	0	0	1	1
Overall Study	SERIOUS EVENT OF ASTHMA EXACERBATION	1	0	0	0

Baseline characteristics

Characteristic	PLACEBO	MEDI528 0.3 mg/kg	MEDI528 1 mg/kg	MEDI528 3 mg/kg	Total
Age Continuous	38.6 Years STANDARD_DEVIATION 13.2	38.2 Years STANDARD_DEVIATION 16.3	33.2 Years STANDARD_DEVIATION 11.9	28.9 Years STANDARD_DEVIATION 10.7	34.7 Years STANDARD_DEVIATION 13.2
Sex: Female, Male Female	8 Participants	8 Participants	5 Participants	5 Participants	26 Participants
Sex: Female, Male Male	1 Participants	1 Participants	4 Participants	4 Participants	10 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	9 / 9	9 / 9	9 / 9	9 / 9
serious Total, serious adverse events	1 / 9	0 / 9	0 / 9	0 / 9

Outcome results

Primary