Churg Strauss Syndrome
Conditions
Keywords
Churg Strauss Syndrome
Brief summary
The purpose of this study is to determine whether Mepolizumab (a monoclonal antibody against interleukin-5) is a safe and well-tolerated therapy that will allow for steroid tapering in patients with steroid-dependent Churg-Strauss Syndrome (CSS).
Detailed description
Specific Aims: 1. Document the safety of mepolizumab therapy in patients with CSS. 2. Demonstrate the steroid sparing effect of mepolizumab therapy by decreasing corticosteroid dosage while using this anti-IL5 therapy. 3. Demonstrate the efficacy of anti-IL5 therapy in improving the signs and symptoms of CSS by: 1. Measuring serum markers of CSS disease activity, including: peripheral eosinophilia, erythrocyte sedimentation rate, anti- neutrophil cytoplasmic antigen, C-reactive protein and IgE levels. 2. Assessing the activity level of vasculitis via the Birmingham Vasculitis Activity Score 3. Evaluating asthmatic response via serial peak flow and FEV1 measurements as well as asthma symptom scores using the Juniper scale. 4. Assessing changes in novel parameters such as fractional excretion of nitric oxide and IL-5 levels.
Interventions
BIOLOGICALMepolizumab
IV mepolizumab, 750 mg
Sponsors
GlaxoSmithKline
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years old * Diagnosis of Churg Strauss Syndrome * Maintained on stable corticosteroid dose of at least prednisone 10mg daily (or equivalent) prior to enrollment in study * If on cyclophosphamide, azathioprine or methotrexate, must be on a stable dose and be able to maintain that dose for the duration of the study
Exclusion criteria
* Hypereosinophilic Syndrome * Wegener's Granulomatosis * Malignancy * Parasitic Disease * Pregnant or nursing * If female and of child-bearing potential, must have negative pregnancy test prior to each infusion of study medication and must adhere to acceptable method of contraception (with \<1% failure rate) * Any other medical illness that precludes study involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Indicated Side Effects | Participants were followed for the duration of the study, approximately 44 weeks | Side effects experienced by participants 1 to 2 days after Mepolizumab infusion. |
| Number of Participants Who Experienced Specific Symptoms | 44 weeks | Number of participants who experienced specific symptoms during the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steroid Dosing During Trial | 20 weeks | — |
| Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims | 20 weeks | The Asthma Control Questionnaire (ACQ) was one measure used to assess the prevalence of asthma symptoms the participant was having during the study. It is a series of 7 questions assessing how often, over the past two weeks, the participant wakes up from their asthma, how bad their symptoms were, etc. The greater the prevalence of symptoms, the higher the score. Each of the 7 questions is scored 0-6. The total score is calculated by adding the individual question scores and dividing the sum by 7. |
| Efficacy- Exacerbation Rate | Treatment period (12 weeks) | Quantified the exacerbation rate (total number of exacerbations per day) of the participants during treatment with mepolizumab and without treatment. Exacerbations were characterized as any worsening of clinical disease requiring an increase of systemic corticosteroid therapy (e.g. prednisone) for asthma, respiratory symptoms, or underlying vasculitis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab Intravenously infused 750 mg of mepolizumab 1x every 4 weeks for 16 weeks. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Mepolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized Participants Unknown | 3 Participants |
| Race/Ethnicity, Customized Participants # White Participants | 7 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Number of Participants Who Experienced Specific Symptoms
Number of participants who experienced specific symptoms during the trial.
Time frame: 44 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mepolizumab | Number of Participants Who Experienced Specific Symptoms | Wheeze or cough | 4 Participants |
| Mepolizumab | Number of Participants Who Experienced Specific Symptoms | Sore throat | 4 Participants |
| Mepolizumab | Number of Participants Who Experienced Specific Symptoms | Nausea or abdominal discomfort | 3 Participants |
| Mepolizumab | Number of Participants Who Experienced Specific Symptoms | Sinusitis | 6 Participants |
| Mepolizumab | Number of Participants Who Experienced Specific Symptoms | Arthritis | 1 Participants |
Primary
Number of Participants With Indicated Side Effects
Side effects experienced by participants 1 to 2 days after Mepolizumab infusion.
Time frame: Participants were followed for the duration of the study, approximately 44 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mepolizumab | Number of Participants With Indicated Side Effects | Mild transient headaches | 3 Participants |
| Mepolizumab | Number of Participants With Indicated Side Effects | Mild pruritus | 1 Participants |
| Mepolizumab | Number of Participants With Indicated Side Effects | Urticaria, allergic reaction, worsening symptoms | 0 Participants |
| Mepolizumab | Number of Participants With Indicated Side Effects | Loose stool | 1 Participants |
Secondary
Efficacy- Exacerbation Rate
Quantified the exacerbation rate (total number of exacerbations per day) of the participants during treatment with mepolizumab and without treatment. Exacerbations were characterized as any worsening of clinical disease requiring an increase of systemic corticosteroid therapy (e.g. prednisone) for asthma, respiratory symptoms, or underlying vasculitis.
Time frame: Treatment period (12 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab | Efficacy- Exacerbation Rate | 0.14 Exacerbation rate (Exacerbations/day) |
| Non-treatment Phase | Efficacy- Exacerbation Rate | 0.69 Exacerbation rate (Exacerbations/day) |
Secondary
Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims
The Asthma Control Questionnaire (ACQ) was one measure used to assess the prevalence of asthma symptoms the participant was having during the study. It is a series of 7 questions assessing how often, over the past two weeks, the participant wakes up from their asthma, how bad their symptoms were, etc. The greater the prevalence of symptoms, the higher the score. Each of the 7 questions is scored 0-6. The total score is calculated by adding the individual question scores and dividing the sum by 7.
Time frame: 20 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab | Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims | Week 0, baseline | 1.40 units on a scale |
| Mepolizumab | Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims | Week 12, Treatment phase | 1.76 units on a scale |
| Mepolizumab | Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims | Week 20, end of washout phase | 1.30 units on a scale |
Secondary
Steroid Dosing During Trial
Time frame: 20 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab | Steroid Dosing During Trial | Week 20 | 4.9 Prednisone mg/day |
| Mepolizumab | Steroid Dosing During Trial | Baseline (Week 0) | 14.3 Prednisone mg/day |
| Mepolizumab | Steroid Dosing During Trial | Week 12 | 5.6 Prednisone mg/day |