Asthma
Conditions
Brief summary
The primary objective of the study is to demonstrate that dupilumab treatment improves exercise capacity in patients with moderate-to-severe asthma. The secondary objectives of the study are: * To demonstrate that dupilumab treatment increases physical activity of daily living in patients with moderate-to-severe asthma * To demonstrate that dupilumab treatment improves pre- and post-exercise lung function in patients with moderate-to-severe asthma
Interventions
DRUGdupilumab
Pre-filled syringe administered by subcutaneous (SC) injections
DRUGMatching placebo
Pre-filled syringe administered by subcutaneous (SC)
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * A physician diagnosis of asthma * Pre-bronchodilator FEV1 between 30% and 75% predicted at both the screening and baseline visits * Bronchodilator reversibility defined as \>200 mL and 12% increase in FEV1 post-administration of a short-acting beta agonist (SABA). A patient may also qualify if there is a documented history of bronchodilator reversibility or positive methacholine challenge test within 12 months prior to the screening visit * Stable background therapy for at least 3 months with a stable dose ≥4 weeks prior to the baseline visit of a medium-to-high dose ICS (fluticasone propionate ≥250 to 1000 μg twice daily \[BID\] or equivalent) in combination with at least a second controller medication (eg, long-acting beta agonist \[LABA\], long-acting muscarinic antagonist \[LAMA\], leukotriene receptor antagonist \[LTRA\], theophylline, etc.); a third controller is allowed and with the same stabilization requirements * Blood eosinophil count ≥300 cells/μL for patients not on maintenance OCS at the screening visit * ACQ-5 score ≥1.5 at the screening and baseline visits Key
Exclusion criteria
* Body mass index \>35 kg/m2 at screening * Current smoking, vaping or tobacco chewing or cessation of any of these within 6 months prior to randomization, or \>10 pack years smoking history * Patients who require supplemental oxygen at screening * Clinically significant cardiac disease as described in the protocol * Uncontrolled hypertension at screening or baseline * Participation in exercise or physical rehabilitation program within last 6 months prior to screening or planned during the study * Previous use of dupilumab * Anti-IgE therapy (eg, omalizumab \[Xolair®\]) within 130 days prior to visit 1 or any other biologic therapy (including anti-IL5, anti-IL-5R, anti-IL4Rα, anti-IL-13 mAb) or systemic immunosuppressant (eg, methotrexate, any anti-tumor necrosis factor mAbs, Janus kinase inhibitors, B- and/or T-cell targeted immunosuppressive therapies) to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 3 months or 5 half-lives prior to screening, whichever is longer * Exposure to another investigative drug (monoclonal antibodies as well as small molecules) within a period prior to screening, of \<3 months or \<5 half-lives (whichever is longer) * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study * Women of childbearing potential (WOCBP)\* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 12 weeks after the last dose NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Constant Work Rate Exercise Endurance Time - CWRET (Constant Work Rate Exercise Test) | Up to week 12 | CWRET (Constant Work Rate Exercise Test) will be performed on an electromagnetically-braked cycle ergometer in an exercise physiology laboratory overseen by a trained pulmonologist or medical doctor designee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Average Number of Steps Walked Per Day | Up to week 12 | Based on accelerometry data |
| Change From Baseline to Week 12 in Total Energy Expenditure | Up to week 12 | Metabolic equivalents of tasks \[METs\]. Based on accelerometry data |
| Change From Baseline to Week 12 in the Mean Duration of Moderate-to-vigorous Physical Activity | Up to week 12 | Defined as ≥3 METs. Based on accelerometry data |
| Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Up to week 12 | Based on spirometry data |
Countries
France, Germany, Poland, Spain, United States
Participant flow
Pre-assignment details
127 participants screened, 87 screen-fail, 40 participants randomized
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching dupilumab placebo | 20 |
| Dupilumab A loading dose at the start of the treatment followed by once every two weeks (Q2W). | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Did not complete End of Study follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Dupilumab | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 45.3 Years STANDARD_DEVIATION 7.8 | 45.9 Years STANDARD_DEVIATION 7.7 | 46.5 Years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 37 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 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 | 19 Participants | 37 Participants | 18 Participants |
| Sex: Female, Male Female | 8 Participants | 19 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 9 / 20 | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change From Baseline to Week 12 in Constant Work Rate Exercise Endurance Time - CWRET (Constant Work Rate Exercise Test)
CWRET (Constant Work Rate Exercise Test) will be performed on an electromagnetically-braked cycle ergometer in an exercise physiology laboratory overseen by a trained pulmonologist or medical doctor designee.
Time frame: Up to week 12
Population: The full analysis set (FAS) includes all randomized participants. The FAS is based on the treatment allocated (as randomized). Here 'n' = number of evaluable participants at a specified point in time.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in Constant Work Rate Exercise Endurance Time - CWRET (Constant Work Rate Exercise Test) | 0.923 Minutes |
| Dupilumab | Change From Baseline to Week 12 in Constant Work Rate Exercise Endurance Time - CWRET (Constant Work Rate Exercise Test) | 1.742 Minutes |
Secondary
Change From Baseline to Week 12 in Average Number of Steps Walked Per Day
Based on accelerometry data
Time frame: Up to week 12
Population: The full analysis set (FAS) includes all randomized participants. The FAS is based on the treatment allocated (as randomized). Here 'n' = number of evaluable participants at a specified point in time.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in Average Number of Steps Walked Per Day | -1066.11 Steps |
| Dupilumab | Change From Baseline to Week 12 in Average Number of Steps Walked Per Day | 925.92 Steps |
Secondary
Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1)
Based on spirometry data
Time frame: Up to week 12
Population: The full analysis set (FAS) includes all randomized participants. The FAS is based on the treatment allocated (as randomized). Here 'n' = number of evaluable participants at a specified point in time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (20-min Post-Exercise) | 0.2496 Liters |
| Placebo | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (Pre-exercise) | 0.2123 Liters |
| Placebo | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (2-min Post-Exercise) | 0.2550 Liters |
| Placebo | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (5-min Post-Exercise) | 0.2416 Liters |
| Placebo | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (10-min Post-Exercise) | 0.2211 Liters |
| Dupilumab | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (10-min Post-Exercise) | 0.4613 Liters |
| Dupilumab | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (5-min Post-Exercise) | 0.4156 Liters |
| Dupilumab | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (Pre-exercise) | 0.4205 Liters |
| Dupilumab | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (20-min Post-Exercise) | 0.4738 Liters |
| Dupilumab | Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1) | Change from Baseline to Week 12 (2-min Post-Exercise) | 0.2902 Liters |
Secondary
Change From Baseline to Week 12 in the Mean Duration of Moderate-to-vigorous Physical Activity
Defined as ≥3 METs. Based on accelerometry data
Time frame: Up to week 12
Population: The full analysis set (FAS) includes all randomized participants. The FAS is based on the treatment allocated (as randomized). Here 'n' = number of evaluable participants at a specified point in time.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in the Mean Duration of Moderate-to-vigorous Physical Activity | -11.01 Minutes |
| Dupilumab | Change From Baseline to Week 12 in the Mean Duration of Moderate-to-vigorous Physical Activity | 9.38 Minutes |
Secondary
Change From Baseline to Week 12 in Total Energy Expenditure
Metabolic equivalents of tasks \[METs\]. Based on accelerometry data
Time frame: Up to week 12
Population: The full analysis set (FAS) includes all randomized participants. The FAS is based on the treatment allocated (as randomized). Here 'n' = number of evaluable participants at a specified point in time.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in Total Energy Expenditure | 23.40 METs (metabolic equivalent of task) |
| Dupilumab | Change From Baseline to Week 12 in Total Energy Expenditure | 59.36 METs (metabolic equivalent of task) |