Allergic Asthma
Conditions
Keywords
Asthma
Brief summary
A single center pilot study to determine the protective effects of RhuMAB-E25 on airway physiology and biology in allergic asthmatics that undergo bronchoprovocation with methacholine. The primary study objective determines the protective impact of RhuMAB-E25 on airway inflammation as reflected in exhaled nitric oxide (NO) levels in allergic asthmatics. The secondary objective determines the protective effect of rhuMAB E25 against airway bronchoconstriction as reflected in the Provocative Concentration of methacholine to cause a 20% fall in FEV1(PC20) with methacholine challenge testing.
Detailed description
This is a single center prospective, open-label study. Eligible subjects will undergo two baseline measurements of exhaled Nitric Oxide (NO) before and after methacholine challenge testing at least one week apart. All subjects will receive treatment with RhuMAB-E25 in an open label fashion at day 0, weeks 4 and 8, and undergo methacholine challenge and NO measurement at screening/baseline, weeks 0, 6, and 12. Complete Blood Count (CBC) will be done at screening/baseline, weeks 1, 2, 4, 8, and week 12. For women of childbearing potential, a screening pregnancy test will be done. All statistical analysis will occur at the conclusion of this study.
Interventions
DRUGRhuMab-E25
three subcutaneous injections spaced 1 month apart; dose based on subject weight and baseline IgE level.
Sponsors
Genentech, Inc.
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be at least 18 years of age, * Must have an FEV1 of \> 70% of predicted, * Must have evidence of bronchial hyperreactivity to methacholine as defined by a methacholine provocation causing a 20% or greater fall in FEV1 (PC20) \< 8 mg/ml * Use of inhaled steroid is permitted; however, no change in inhaled steroid dosage will be permitted over the duration of study * Must have a normal platelet count, * Must be willing to and competent to sign the consent form
Exclusion criteria
* Subjects that do not have allergic asthma will be excluded. * Subjects with ER visits or upper respiratory infections within the last six weeks will be excluded. * Subjects with tobacco use within the past year or \> 10 pack year history of tobacco use will be excluded. * Subjects with serum IgE levels of less than 30 or greater than 700 Iu/mL will be excluded. * Subjects that require oral steroid use will be excluded. * Subjects who weigh \< 30 kg or \> 150 kg are excluded, and subjects with baseline IgE levels greater than 300 may be excluded, depending on weight * Pregnant or nursing females will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Exhaled Nitric Oxide From Baseline to Week 12 | 13 weeks | The primary outcome measure was the change in exhaled nitric oxide levels between baseline and week 12. 12 week value minus baseline value. (Baseline was -1 week, ie 1 week prior to the start of study drug) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Pulmonary clinic and the local community from 10/2002 - 07/2004
Pre-assignment details
The majority of screen failures prior to starting study drug was one of 3 reasons; negative methacholine challenge, IgE, too low, or IgE too high.
Participants by arm
| Arm | Count |
|---|---|
| RhuMab-E25 | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | RhuMab-E25 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 31.8 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Change in Exhaled Nitric Oxide From Baseline to Week 12
The primary outcome measure was the change in exhaled nitric oxide levels between baseline and week 12. 12 week value minus baseline value. (Baseline was -1 week, ie 1 week prior to the start of study drug)
Time frame: 13 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RhuMab-E25 | Change in Exhaled Nitric Oxide From Baseline to Week 12 | -11.0 parts per billion (ppb) | Standard Deviation 13.3 |
p-value: 0.005Sign test