Non-Eosinophilic Asthma
Conditions
Keywords
Non-Eosinophilic Asthma, AVTX-002
Brief summary
The primary objective of this study is to evaluate the efficacy of AVTX-002 compared with placebo in patients with poorly controlled non-eosinophilic asthma (NEA).
Interventions
DRUGAVTX-002
Dose of 600 mg administered subcutaneously three times during the study.
DRUGPlacebo
Placebo sourced as normal saline administered subcutaneously three times during the study.
Sponsors
Avalo Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented non-eosinophilic asthma diagnosis (\<300 eosinophils/μL). * Symptoms consistent with a diagnosis of asthma that is poorly controlled as determined by an ACQ score ≥ 1.5. * Poorly controlled asthma despite the use of a Long-Acting Beta-Agonists and Inhaled Corticosteroid for at least 3 consecutive months immediately prior to screening. * Subjects must have had at least one asthma exacerbation in the last 24 months.
Exclusion criteria
* Pulmonary disease other than asthma. * Currently on biologic therapy. Previous biologic therapy is permitted with adequate washout (12 weeks or 5 half-lives, whichever is longer). * Use of systemic immunosuppressants within the last 6 months. * Use of systemic corticosteroids within 6 weeks prior to Screening or use of antibiotics within 4 weeks prior to Screening. * Subject has alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) \>5 upper limit of normal (ULN) and/or serum creatinine concentration \>1.5 mg/dL. * Subject has hemoglobin ≤10 g/dL, neutrophils ≤1,500/μl, and/or platelets ≤75,000/μl.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events. | Through Week 14 | Percentage of patients who experience any of the following asthma related events: * ≥6 additional reliever puffs of Short-Acting Beta-Agonist (compared to baseline) in a 24-hour period on 2 consecutive days or, * increase in inhaled corticosteroid dose ≥4 times than the dose at baseline or, * a decrease in peak flow of 30% or more (compared to baseline) on 2 consecutive days of treatment, or * an asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days, or * a hospitalization or emergency room visit because of an asthma exacerbation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Asthma Exacerbation. | Through Week 14 | Time to event will be measured in days using the first day of the event to denote the day of the overall asthma related event occurrence. |
| Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO). | Through Week 14 | A FeNO test measures the levels of nitric oxide during exhalation. A FeNO test will be done by breathing into a tube attached to a hand-held monitor. |
| Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ). | Through Week 14 | This is a simple questionnaire to measure the adequacy of asthma control and change in asthma control. ACQ has a multidimensional construct assessing symptoms (5 items, self-administered), rescue bronchodilator use (1 item, self-administered), and FEV1 (1 item, completed by study staff). Scores range between 0 (totally controlled) and 6 (severely uncontrolled). |
| Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12). | Through Week 14 | The AQLQ(S)+12 is a modified version of the standardized AQLQ and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Subjects will be asked to recall their experiences during the previous 2 weeks and score each of the questions on a 7-point scale, where 7=not at all limited and 1=totally limited. The overall score of the AQLQ +12 will be derived as the average of the 32 questions; thus, the total score ranges from 1 (indicates total impairment) to 7 (indicates no impairment). |
| Change From Baseline to Week 14 in Asthma Symptom Diary Score. | Through Week 14 | The Asthma Symptom Diary is a 6-item daily measure of asthma symptom severity that assesses three core categories of asthma symptoms: breathing symptoms (difficulty breathing; wheezing; shortness of breath), chest symptoms (chest tightness; chest pain), and cough. Subjects are required to rate the 6 symptoms at their worst each day using an 11-point numeric rating scale ranging from 0 ('None') to 10 ('As bad as you can imagine'). The Asthma Symptom Diary score is the sum of the 6 individual symptom scores (the range is from 0-60, where a higher score indicates more severe symptoms) reported as a weekly average. |
| Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]). | Through Week 14 | The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters by a spirometer. |
| Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. | Through Week 14 | The Patient Global Impression of Change (PGI-C) is a single question scale asking the patient to rate the overall status of their specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Patient Global Impression of Severity (PGI-S) is a single question scale asking the patient to rate current state of their specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme). |
| Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. | Through Week 14 | The Clinician Global Impression of Improvement (CGI-I) is a single question scale asking clinician to rate the overall status of the patient's specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Clinician Global Impression of Severity (CGI-S) is a single question scale asking the clinician to rate current state of the patient's specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme). |
| The Number of Inhalations of Short-acting Beta Agonist (SABA) at Week 14. | Through Week 14 | The number of times a short-acting beta agonist (number of inhalations) was used was assessed daily and reported as a weekly average. |
| Change From Baseline to Week 14 in Serum Soluble LIGHT Levels (Lymphotoxin-like, Exhibits Inducible Expression, and Competes With Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a Receptor Expressed by T Lymphocytes). | Through Week 14 | Change from baseline in serum soluble LIGHT levels. |
| Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14. | Incidence of anti-drug antibodies (ADAs) at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14. |
| Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS). | Through Week 14 | The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ VAS. The EQ VAS records the subject's self-rated health on a vertical VAS with a score of 0-100, where the endpoints are labelled 0 for 'The worst health you can imagine' and 100 for 'The best health you can imagine'. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVTX-002 AVTX-002: Dose of 600 mg administered subcutaneously three times during the study. | 45 |
| Placebo Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study. | 46 |
| Total | 91 |
Baseline characteristics
| Characteristic | AVTX-002 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 14.6 | 47.6 years STANDARD_DEVIATION 15.99 | 46.6 years STANDARD_DEVIATION 15.27 |
| BMI | 33.95 kg/m^2 STANDARD_DEVIATION 8.917 | 31.20 kg/m^2 STANDARD_DEVIATION 6.329 | 32.56 kg/m^2 STANDARD_DEVIATION 7.798 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 12 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 34 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 168.41 cm STANDARD_DEVIATION 9.9 | 167.69 cm STANDARD_DEVIATION 10.865 | 168.04 cm STANDARD_DEVIATION 10.347 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 10 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 35 Participants | 63 Participants |
| Region of Enrollment United States | 45 participants | 46 participants | 91 participants |
| Screening eosinophil level < 150 eosinophils per micro liter | 24 Participants | 25 Participants | 49 Participants |
| Screening eosinophil level >= 150 eosinophils per micro liter | 21 Participants | 21 Participants | 42 Participants |
| Sex: Female, Male Female | 28 Participants | 32 Participants | 60 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 31 Participants |
| Weight | 95.60 kg STANDARD_DEVIATION 23.661 | 87.94 kg STANDARD_DEVIATION 21.343 | 91.73 kg STANDARD_DEVIATION 22.722 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 45 |
| other Total, other adverse events | 19 / 45 | 21 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events.
Percentage of patients who experience any of the following asthma related events: * ≥6 additional reliever puffs of Short-Acting Beta-Agonist (compared to baseline) in a 24-hour period on 2 consecutive days or, * increase in inhaled corticosteroid dose ≥4 times than the dose at baseline or, * a decrease in peak flow of 30% or more (compared to baseline) on 2 consecutive days of treatment, or * an asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days, or * a hospitalization or emergency room visit because of an asthma exacerbation
Time frame: Through Week 14
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AVTX-002 | The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events. | 12 Participants |
| Placebo | The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events. | 14 Participants |
Secondary
Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ).
This is a simple questionnaire to measure the adequacy of asthma control and change in asthma control. ACQ has a multidimensional construct assessing symptoms (5 items, self-administered), rescue bronchodilator use (1 item, self-administered), and FEV1 (1 item, completed by study staff). Scores range between 0 (totally controlled) and 6 (severely uncontrolled).
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ). | -0.22 score on a scale | Standard Deviation 1.077 |
| Placebo | Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ). | -0.34 score on a scale | Standard Deviation 0.999 |
Secondary
Change From Baseline to Week 14 in Asthma Symptom Diary Score.
The Asthma Symptom Diary is a 6-item daily measure of asthma symptom severity that assesses three core categories of asthma symptoms: breathing symptoms (difficulty breathing; wheezing; shortness of breath), chest symptoms (chest tightness; chest pain), and cough. Subjects are required to rate the 6 symptoms at their worst each day using an 11-point numeric rating scale ranging from 0 ('None') to 10 ('As bad as you can imagine'). The Asthma Symptom Diary score is the sum of the 6 individual symptom scores (the range is from 0-60, where a higher score indicates more severe symptoms) reported as a weekly average.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Asthma Symptom Diary Score. | -0.15 units on a scale | Standard Deviation 1.469 |
| Placebo | Change From Baseline to Week 14 in Asthma Symptom Diary Score. | -0.39 units on a scale | Standard Deviation 1.318 |
Secondary
Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity.
The Clinician Global Impression of Improvement (CGI-I) is a single question scale asking clinician to rate the overall status of the patient's specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Clinician Global Impression of Severity (CGI-S) is a single question scale asking the clinician to rate current state of the patient's specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme).
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. | CGI-S | -0.3 units on a scale | Standard Deviation 0.86 |
| AVTX-002 | Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. | CGI-I | 3.4 units on a scale | Standard Deviation 1.32 |
| Placebo | Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. | CGI-S | -0.5 units on a scale | Standard Deviation 1.33 |
| Placebo | Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. | CGI-I | 3.2 units on a scale | Standard Deviation 1.52 |
Secondary
Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS).
The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ VAS. The EQ VAS records the subject's self-rated health on a vertical VAS with a score of 0-100, where the endpoints are labelled 0 for 'The worst health you can imagine' and 100 for 'The best health you can imagine'.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS). | 2.9 units on a scale | Standard Deviation 22.6 |
| Placebo | Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS). | 5.6 units on a scale | Standard Deviation 15.28 |
Secondary
Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]).
The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters by a spirometer.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]). | -0.149 Liter | Standard Deviation 0.309 |
| Placebo | Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]). | -0.203 Liter | Standard Deviation 0.405 |
Secondary
Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO).
A FeNO test measures the levels of nitric oxide during exhalation. A FeNO test will be done by breathing into a tube attached to a hand-held monitor.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO). | 6.1 Parts per billion | Standard Deviation 15.54 |
| Placebo | Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO). | 3.8 Parts per billion | Standard Deviation 27.64 |
Secondary
Change From Baseline to Week 14 in Patient Global Impression of Change/Severity.
The Patient Global Impression of Change (PGI-C) is a single question scale asking the patient to rate the overall status of their specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Patient Global Impression of Severity (PGI-S) is a single question scale asking the patient to rate current state of their specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme).
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. | PGI-S | 0.0 units on a scale | Standard Deviation 1.28 |
| AVTX-002 | Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. | PGI-C | 3.4 units on a scale | Standard Deviation 1.5 |
| Placebo | Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. | PGI-S | -0.4 units on a scale | Standard Deviation 1.31 |
| Placebo | Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. | PGI-C | 3.0 units on a scale | Standard Deviation 1.63 |
Secondary
Change From Baseline to Week 14 in Serum Soluble LIGHT Levels (Lymphotoxin-like, Exhibits Inducible Expression, and Competes With Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a Receptor Expressed by T Lymphocytes).
Change from baseline in serum soluble LIGHT levels.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Serum Soluble LIGHT Levels (Lymphotoxin-like, Exhibits Inducible Expression, and Competes With Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a Receptor Expressed by T Lymphocytes). | -114.52 pg/mL | Standard Deviation 80.781 |
| Placebo | Change From Baseline to Week 14 in Serum Soluble LIGHT Levels (Lymphotoxin-like, Exhibits Inducible Expression, and Competes With Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a Receptor Expressed by T Lymphocytes). | 11.63 pg/mL | Standard Deviation 92.147 |
Secondary
Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12).
The AQLQ(S)+12 is a modified version of the standardized AQLQ and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Subjects will be asked to recall their experiences during the previous 2 weeks and score each of the questions on a 7-point scale, where 7=not at all limited and 1=totally limited. The overall score of the AQLQ +12 will be derived as the average of the 32 questions; thus, the total score ranges from 1 (indicates total impairment) to 7 (indicates no impairment).
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12). | 0.18 score on a scale | Standard Deviation 1.423 |
| Placebo | Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12). | 0.49 score on a scale | Standard Deviation 1.162 |
Secondary
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint.
Incidence of anti-drug antibodies (ADAs) at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14.
Population: Safety Analysis Set: Data only collected for AVTX-002 Arm/Group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Baseline | 0 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 2 | 1 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 4 | 0 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 6 | 0 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 8 | 0 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 12 | 0 Participants |
| AVTX-002 | Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. | Week 14 | 0 Participants |
Secondary
The Number of Inhalations of Short-acting Beta Agonist (SABA) at Week 14.
The number of times a short-acting beta agonist (number of inhalations) was used was assessed daily and reported as a weekly average.
Time frame: Through Week 14
Population: Full Analysis Set with all subjects with baseline and Week 14 data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVTX-002 | The Number of Inhalations of Short-acting Beta Agonist (SABA) at Week 14. | 1.28 number of inhalations | Standard Deviation 1.507 |
| Placebo | The Number of Inhalations of Short-acting Beta Agonist (SABA) at Week 14. | 0.97 number of inhalations | Standard Deviation 1.695 |
Secondary
Time to Asthma Exacerbation.
Time to event will be measured in days using the first day of the event to denote the day of the overall asthma related event occurrence.
Time frame: Through Week 14
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVTX-002 | Time to Asthma Exacerbation. | Time to first asthma related event or time to censoring | 84.9 days | Standard Deviation 28.03 |
| AVTX-002 | Time to Asthma Exacerbation. | Time to first asthma related event - Subjects with an asthma related event | 52.1 days | Standard Deviation 31.83 |
| Placebo | Time to Asthma Exacerbation. | Time to first asthma related event or time to censoring | 78.1 days | Standard Deviation 30.58 |
| Placebo | Time to Asthma Exacerbation. | Time to first asthma related event - Subjects with an asthma related event | 42.6 days | Standard Deviation 26.69 |