STRATOS1: A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02161757
Collaborator
(none)
1,207
243
4
37.2
5
0.1
Study Details
Study Description
Brief Summary
A 52-Week, Multicentre, Randomized, Double-Blind, Parallel Group, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents with Asthma Inadequately Controlled on Inhaled Corticosteroid Plus Long-Acting β2-Agonist
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a randomized, double-blind, parallel group, placebo-controlled study designed to evaluate efficacy and safety of tralokinumab administered subcutaneously in subjects with uncontrolled asthma on inhaled corticosteroid plus long-acting β2-agonist and having a history of asthma exacerbations.
Approximately 1140 subjects will be randomized globally. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1207 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Asthma Inadequately Controlled on Inhaled Corticosteroid Plus Long-Acting β2-Agonist.
Actual Study Start Date
:
Jun 13, 2014
Actual Primary Completion Date
:
Feb 28, 2017
Actual Study Completion Date
:
Jul 18, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tralokinumab Dose Regimen 1 Tralokinumab subcutaneous injection |
Biological: Tralokinumab
Subcutaneous injection
|
| Placebo Comparator: Placebo Dose Regimen 1 Placebo subcutaneous injection |
Other: Placebo
Subcutaneous injection
|
| Experimental: Tralokinumab Dose Regimen 2 Tralokinumab subcutaneous injection |
Biological: Tralokinumab
Subcutaneous injection
|
| Placebo Comparator: Placebo Dose Regimen 2 Placebo subcutaneous injection |
Other: Placebo
Subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Annualised Asthma Exacerbation Rate (AAER) up to Week 52 [Baseline (Week 0) up to Week 52]
Asthma exacerbation was defined as a worsening of asthma that led to any of the following: Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for <24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids (see above). An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma. AAER = number of exacerbations*365.25 / (follow-up date - date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks). AAER in the tralokinumab group was compared to that seen in the placebo group up to Week 52 using a negative binomial model; rate ratios and rate reductions are both presented for comparative statistical analyses.
Secondary Outcome Measures
- Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1) [Baseline (Week 0) and Week 52]
Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorised delegate according to American Thoracic Society/European Respiratory Society guidelines. The mean percent change from baseline in pre-BD FEV1 at Week 52 is presented.
- Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means) [Baseline (Week 0) and Week 52]
Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary. Symptoms were recorded using a 4-point response scale, which ranged from 0 to 3, where 0 indicated no asthma symptoms. Asthma symptom daytime score (recorded in the evening), night-time score (recorded in the morning), and total score were calculated separately. The daily asthma symptom total score was calculated by taking the sum of the night-time and daytime asthma symptom scores recorded each day, ranging from 0 to 6. A lower symptom score indicated a better outcome. The change from baseline in bi-weekly mean daily asthma symptom total score is presented.
- Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score [Baseline (Week 0) and Week 52]
The AQLQ(S)+12 is a questionnaire that measures health-related quality of life for patients with asthma aged 12 and older. The questionnaire comprises 32 questions and has 4 separate domains (asthma symptoms, activity limitations, emotional function and environmental stimuli). Patients were asked to recall their experiences during the previous 2 weeks and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The total score was calculated as the mean response to all questions, ranging from 1 (severe impairment) to 7 (no impairment). Individual AQLQ(S)+12 total score changes of ≥0.5 were considered to be clinically meaningful. The mean change from baseline in AQLQ(S)+12 score at Week 52 is presented.
- Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score [Baseline (Week 0) and Week 52]
The ACQ-6 questionnaire is a shortened version of the ACQ (omitting FEV1 measurement) that assesses asthma symptoms (night-time awakenings, symptoms on waking, activity limitation, dyspnoea, wheezing) and rescue short-acting β2-agonists medication use during the past week. Questions were weighted equally and scored on a 7-point scale from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma and a score >1.5 indicates not well-controlled asthma. Individual changes of at least 0.5 were considered to be clinically meaningful. The mean change from baseline in ACQ-6 score at Week 52 is presented.
- AAER Associated With an ER/UC Visit, or a Hospitalisation up to Week 52 [Baseline (Week 0) up to Week 52]
The annual rate of exacerbations associated with an ER/UC visit or hospitalisation up to Week 52 are presented for non-adjudicated data (i.e. events assessed by the Investigator and recorded in the electronic case report form). AAER = Number of Exacerbations*365.25 / (Follow-up date - Date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks).
- Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at Week 52 [Baseline (Week 0) and Week 52]
The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a VAS, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. The mean change from baseline in EQ-5D-5L VAS scores at Week 52 is presented.
- Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means) [Baseline (Week 0) and Week 52]
Salbutamol, albuterol or levalbuterol were used as rescue medication during the study in the event of a worsening of asthma symptoms. Rescue medication use was measured by the bi-weekly mean number of inhalations (puffs) per day, calculated as: total morning puffs + total evening puffs + 2*(total morning nebuliser use + total evening nebuliser use)/ total number of days with data in bi-weekly period. The change from baseline in bi-weekly mean total asthma rescue medication use at Week 52 is presented.
- Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at Week 52 [Baseline (Week 0) and Week 52]
Home PEF testing was performed by the patient using an electronic, hand-held spirometer (peak flow meter) and was performed in the morning upon awakening (prior to taking their morning asthma controller) and in the evening at bedtime (prior to taking their evening asthma controller). The mean change from baseline in home PEF values at Week 52 are presented separately for morning and evening.
- Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage]) [Baseline (Week 0) and Week 52]
The patient captured night-time awakenings (yes/no) and the use of rescue medication during these awakenings (yes/no) each morning in the Asthma Daily Diary. Night-time awakenings (percentage) was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data. The change from baseline in bi-weekly means (percentage) night-time awakenings due to asthma requiring rescue medication use at Week 52 is presented.
- Number of Patients With ≥1 Asthma Exacerbation up to Week 52 [Baseline (Week 0) up to Week 52]
The number of patients with ≥1 asthma exacerbation up to Week 52 is presented.
- Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss at Week 52 [At Week 52]
The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for productivity loss are presented separately for those currently employed and for those currently in school and are expressed as mean productivity loss (percentage) at Week 52, with higher numbers indicating less productivity. Work Productivity Loss = {Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]}*100 (Absenteeism = Q2/(Q2+Q4)*100; Presenteeism = (Q5/10)*100). Class Productivity Loss = {Q7/(Q7+Q8) + [(1-Q7/(Q7+Q8))x(Q9/10)]}*100 (Absenteeism = Q7/ (Q7+Q8)*100; Presenteeism = (Q9/10)*100). Note: QX refers to response to question number X on WPAI+CIQ questionnaire.
- WPAI+CIQ: Activity Impairment at Week 52 [At Week 52]
The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for activity impairment are presented separately for those currently employed and for those currently in school and are expressed as mean impairment percentages at Week 52, with higher numbers indicating greater impairment. Activity impairment = (Q10/10)*100. Note: QX refers to response to question number X on WPAI+CIQ questionnaire.
- Asthma-related Healthcare Encounters by Type up to Week 52 [Baseline (Week 0) up to Week 52]
Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of times the healthcare encounter occurred was calculated across all patients for each of the following categories: Ambulance transport, Emergency room visits, Unscheduled outpatient visits (visit to specialist and/or visit to primary healthcare physician and/or other healthcare visit), Home visits (home visit, physician and/or other healthcare professional), Telephone calls (telephone calls to physician and/or nurse), and Advanced pulmonary function test.
- Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations [Baseline (Week 0) up to Week 52]
Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of days spent in hospital was calculated across all patients for the following healthcare encounter category: • Hospitalisations (hospitalisations, intensive care and/or general care).
- Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry [Baseline (Week 0) up to Week 52]
Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of assessments was calculated across all patients for the following healthcare encounter category: • Spirometry.
- Serum Trough Concentration (Ctrough) of Tralokinumab During the Study Period up to Week 72 [Blood samples were collected pre-dose at Baseline (Week 0), and at Week 4, Week 8, Week 26, Week 52 and Week 72 (follow-up)]
To evaluate the pharmacokinetics (PK), pre-dose blood samples were collected at each visit and tralokinumab concentrations in serum were determined. Mean Ctrough concentrations are presented at each indicated visit up to Week 72.
- Number of Patients Positive for Anti-drug Antibodies (ADAs) [Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)]
ADA assessments performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for neutralising antibodies (nAb). ADA prevalence defined as proportion of study population with drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) defined as sum of treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive defined as having ≥1 post-baseline ADA positive assessment and not fulfilling conditions of persistently positive. Treatment-boosted ADA defined as baseline positive ADA titer boosted to a 4-fold or higher level following drug administration. In some category titles 'positive' is denoted by 'pos'.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 12 -75
-
Documented physician-diagnosed asthma.
-
Documented treatment with ICS at a total daily dose corresponding to ≥500μg fluticasone propionate dry powder formulation equivalents) and a LABA
-
Morning pre-BD FEV1 value of ≥40 and <80% value (<90% for patients 12 to 17 years of age) of their PNV.
-
Post-BD reversibility of ≥12% and ≥200 mL in FEV1
-
ACQ-6 score ≥1.5
Exclusion Criteria:
-
Pulmonary disease other than asthma
-
History of anaphylaxis following any biologic therapy
-
Hepatitis B, C or HIV
-
Pregnant or breastfeeding
-
History of cancer
-
Current tobacco smoking or a history of tobacco smoking for ≥ 10 pack-years
-
Previous receipt of tralokinumab
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | 35209 |
| 2 | Research Site | Phoenix | Arizona | United States | 85018 |
| 3 | Research Site | Arcadia | California | United States | 91007 |
| 4 | Research Site | Los Angeles | California | United States | 90036 |
| 5 | Research Site | Los Angeles | California | United States | 90048 |
| 6 | Research Site | Newport Beach | California | United States | 92663 |
| 7 | Research Site | Poway | California | United States | 92064 |
| 8 | Research Site | San Jose | California | United States | 95117 |
| 9 | Research Site | Tustin | California | United States | 92780 |
| 10 | Research Site | Wildomar | California | United States | 92595 |
| 11 | Research Site | Colorado Springs | Colorado | United States | 80907 |
| 12 | Research Site | Denver | Colorado | United States | 80206 |
| 13 | Research Site | Denver | Colorado | United States | 80246 |
| 14 | Research Site | New Haven | Connecticut | United States | 06519 |
| 15 | Research Site | Clearwater | Florida | United States | 33765 |
| 16 | Research Site | Coral Gables | Florida | United States | 33134 |
| 17 | Research Site | Cutler Bay | Florida | United States | 33189 |
| 18 | Research Site | Fort Lauderdale | Florida | United States | 33308 |
| 19 | Research Site | Hialeah | Florida | United States | 33012 |
| 20 | Research Site | Hialeah | Florida | United States | 33013 |
| 21 | Research Site | Homestead | Florida | United States | 33030 |
| 22 | Research Site | Homestead | Florida | United States | 33130 |
| 23 | Research Site | Jacksonville | Florida | United States | 32277 |
| 24 | Research Site | Kissimmee | Florida | United States | 34741 |
| 25 | Research Site | Miami | Florida | United States | 33125 |
| 26 | Research Site | Miami | Florida | United States | 33126 |
| 27 | Research Site | Miami | Florida | United States | 33134 |
| 28 | Research Site | Miami | Florida | United States | 33135 |
| 29 | Research Site | Miami | Florida | United States | 33144 |
| 30 | Research Site | Miami | Florida | United States | 33145 |
| 31 | Research Site | Miami | Florida | United States | 33155 |
| 32 | Research Site | Miami | Florida | United States | 33166 |
| 33 | Research Site | Miami | Florida | United States | 33173 |
| 34 | Research Site | Miami | Florida | United States | 33174 |
| 35 | Research Site | Miami | Florida | United States | 33175 |
| 36 | Research Site | Miami | Florida | United States | 33176 |
| 37 | Research Site | Ormond Beach | Florida | United States | 32174 |
| 38 | Research Site | Pembroke Pines | Florida | United States | 33029 |
| 39 | Research Site | Winter Park | Florida | United States | 32789 |
| 40 | Research Site | Albany | Georgia | United States | 31707 |
| 41 | Research Site | Atlanta | Georgia | United States | 30331 |
| 42 | Research Site | Lawrenceville | Georgia | United States | 30046 |
| 43 | Research Site | Meridian | Idaho | United States | 83642 |
| 44 | Research Site | Twin Falls | Idaho | United States | 83301 |
| 45 | Research Site | Fort Wayne | Indiana | United States | 46804 |
| 46 | Research Site | South Bend | Indiana | United States | 46617 |
| 47 | Research Site | Bowling Green | Kentucky | United States | 42101 |
| 48 | Research Site | Bangor | Maine | United States | 04401 |
| 49 | Research Site | Brockton | Massachusetts | United States | 2301 |
| 50 | Research Site | Ann Arbor | Michigan | United States | 48106 |
| 51 | Research Site | Farmington Hills | Michigan | United States | 48334 |
| 52 | Research Site | Flint | Michigan | United States | 48504 |
| 53 | Research Site | Ypsilanti | Michigan | United States | 48197 |
| 54 | Research Site | Chesterfield | Missouri | United States | 63017 |
| 55 | Research Site | Saint Louis | Missouri | United States | 63141 |
| 56 | Research Site | Saint Louis | Missouri | United States | 63143 |
| 57 | Research Site | Missoula | Montana | United States | 59808 |
| 58 | Research Site | Las Vegas | Nevada | United States | 89123 |
| 59 | Research Site | Union | New Jersey | United States | 07083 |
| 60 | Research Site | Brooklyn | New York | United States | 11229 |
| 61 | Research Site | Asheville | North Carolina | United States | 28801 |
| 62 | Research Site | Charlotte | North Carolina | United States | 28277 |
| 63 | Research Site | Cornelius | North Carolina | United States | 28031 |
| 64 | Research Site | Hickory | North Carolina | United States | 28078 |
| 65 | Research Site | Shelby | North Carolina | United States | 28150 |
| 66 | Research Site | Winston-Salem | North Carolina | United States | 27104 |
| 67 | Research Site | Columbus | Ohio | United States | 43235 |
| 68 | Research Site | Middleburg Heights | Ohio | United States | 44130 |
| 69 | Research Site | Toledo | Ohio | United States | 43617 |
| 70 | Research Site | Oklahoma City | Oklahoma | United States | 73112 |
| 71 | Research Site | Oklahoma City | Oklahoma | United States | 73131 |
| 72 | Research Site | Monroeville | Pennsylvania | United States | 15146 |
| 73 | Research Site | Philadelphia | Pennsylvania | United States | 19115 |
| 74 | Research Site | Scottdale | Pennsylvania | United States | 15683 |
| 75 | Research Site | Uniontown | Pennsylvania | United States | 15683 |
| 76 | Research Site | Johnston | Rhode Island | United States | 02919 |
| 77 | Research Site | Providence | Rhode Island | United States | 02908 |
| 78 | Research Site | Warwick | Rhode Island | United States | 02886 |
| 79 | Research Site | Anderson | South Carolina | United States | 29621 |
| 80 | Research Site | Greenville | South Carolina | United States | 29607 |
| 81 | Research Site | Myrtle Beach | South Carolina | United States | 29588 |
| 82 | Research Site | Spartanburg | South Carolina | United States | 29303 |
| 83 | Research Site | Boerne | Texas | United States | 78006 |
| 84 | Research Site | Corsicana | Texas | United States | 75110 |
| 85 | Research Site | Dallas | Texas | United States | 75225 |
| 86 | Research Site | Fort Worth | Texas | United States | 76104 |
| 87 | Research Site | Fort Worth | Texas | United States | 76109 |
| 88 | Research Site | Houston | Texas | United States | 77043 |
| 89 | Research Site | Houston | Texas | United States | 77084 |
| 90 | Research Site | Houston | Texas | United States | 77099 |
| 91 | Research Site | Lampasas | Texas | United States | 76550 |
| 92 | Research Site | McKinney | Texas | United States | 75069 |
| 93 | Research Site | Plano | Texas | United States | 75093 |
| 94 | Research Site | San Antonio | Texas | United States | 78218 |
| 95 | Research Site | San Antonio | Texas | United States | 78258 |
| 96 | Research Site | Murray | Utah | United States | 84107 |
| 97 | Research Site | Provo | Utah | United States | 84604 |
| 98 | Research Site | Salt Lake City | Utah | United States | 84102 |
| 99 | Research Site | South Burlington | Vermont | United States | 05403 |
| 100 | Research Site | Arlington | Virginia | United States | 22203 |
| 101 | Research Site | Richmond | Virginia | United States | 23225 |
| 102 | Research Site | Richland | Washington | United States | 99352 |
| 103 | Research Site | Tacoma | Washington | United States | 98405 |
| 104 | Research Site | Buenos Aires | Argentina | C1414AIF | |
| 105 | Research Site | Caba | Argentina | C1425BEN | |
| 106 | Research Site | Cap. Fed | Argentina | 1280 | |
| 107 | Research Site | Ciudad Autonomade Buenos Aires | Argentina | 1426 | |
| 108 | Research Site | Concepción del Uruguay | Argentina | 3260 | |
| 109 | Research Site | Córdoba | Argentina | X5003DCE | |
| 110 | Research Site | Mendoza | Argentina | 5500 | |
| 111 | Research Site | Mendoza | Argentina | M5500GIP | |
| 112 | Research Site | Quilmes | Argentina | B1878FNR | |
| 113 | Research Site | Rosario | Argentina | S2000DEJ | |
| 114 | Research Site | San Miguel de Tucuman | Argentina | 4000 | |
| 115 | Research Site | Brussels (Anderlecht) | Belgium | 1070 | |
| 116 | Research Site | Erpent | Belgium | 5101 | |
| 117 | Research Site | Leuven | Belgium | 3000 | |
| 118 | Research Site | Liège | Belgium | 4000 | |
| 119 | Research Site | Dupnitsa | Bulgaria | 2600 | |
| 120 | Research Site | Kozloduy | Bulgaria | 3320 | |
| 121 | Research Site | Pazardzhik | Bulgaria | 4400 | |
| 122 | Research Site | Pernik | Bulgaria | 2307 | |
| 123 | Research Site | Ruse | Bulgaria | 7002 | |
| 124 | Research Site | Sliven | Bulgaria | 8800 | |
| 125 | Research Site | Sofia | Bulgaria | 1202 | |
| 126 | Research Site | Sofia | Bulgaria | 1407 | |
| 127 | Research Site | Sofia | Bulgaria | 1618 | |
| 128 | Research Site | Stara Zagora | Bulgaria | 6000 | |
| 129 | Research Site | Varna | Bulgaria | 9000 | |
| 130 | Research Site | Veliko Tarnovo | Bulgaria | 5000 | |
| 131 | Research Site | Vratsa | Bulgaria | 3000 | |
| 132 | Research Site | Yambol | Bulgaria | 8600 | |
| 133 | Research Site | Armenia | Colombia | 630004 | |
| 134 | Research Site | Bogotá | Colombia | 110311 | |
| 135 | Research Site | Bogotá | Colombia | ||
| 136 | Research Site | Cali | Colombia | 76001000 | |
| 137 | Research Site | Aschaffenburg | Germany | 63739 | |
| 138 | Research Site | Augsburg | Germany | 86150 | |
| 139 | Research Site | Bad Lippspringe | Germany | 33175 | |
| 140 | Research Site | Geesthacht | Germany | 21502 | |
| 141 | Research Site | Herford | Germany | 32049 | |
| 142 | Research Site | Landsberg | Germany | 86899 | |
| 143 | Research Site | Leipzig | Germany | 04357 | |
| 144 | Research Site | München-Pasing | Germany | 81241 | |
| 145 | Research Site | Reinfeld | Germany | 23858 | |
| 146 | Research Site | Rodgau-Dudenhofen | Germany | 63110 | |
| 147 | Research Site | Warendorf | Germany | 48231 | |
| 148 | Research Site | Balassagyarmat | Hungary | 2660 | |
| 149 | Research Site | Edelény | Hungary | 3780 | |
| 150 | Research Site | Farkasgyepü | Hungary | 8582 | |
| 151 | Research Site | Komárom | Hungary | 2900 | |
| 152 | Research Site | Létavértes | Hungary | 4281 | |
| 153 | Research Site | Miskolc | Hungary | 3529 | |
| 154 | Research Site | Pécs | Hungary | 7626 | |
| 155 | Research Site | Pécs | Hungary | 7635 | |
| 156 | Research Site | Százhalombatta | Hungary | 2440 | |
| 157 | Research Site | Bucheon-si | Korea, Republic of | 14584 | |
| 158 | Research Site | Cheongju-si | Korea, Republic of | 362-804 | |
| 159 | Research Site | Daegu | Korea, Republic of | 42415 | |
| 160 | Research Site | Incheon | Korea, Republic of | 21431 | |
| 161 | Research Site | Incheon | Korea, Republic of | 405-760 | |
| 162 | Research Site | Jeju-si | Korea, Republic of | 63241 | |
| 163 | Research Site | Seoul | Korea, Republic of | 02559 | |
| 164 | Research Site | Seoul | Korea, Republic of | 03080 | |
| 165 | Research Site | Seoul | Korea, Republic of | 03722 | |
| 166 | Research Site | Seoul | Korea, Republic of | 05505 | |
| 167 | Research Site | Seoul | Korea, Republic of | 06591 | |
| 168 | Research Site | Seoul | Korea, Republic of | 08308 | |
| 169 | Research Site | Seoul | Korea, Republic of | 135-710 | |
| 170 | Research Site | Seoul | Korea, Republic of | 150-713 | |
| 171 | Research Site | Suwon-si | Korea, Republic of | 16499 | |
| 172 | Research Site | Cusco | Peru | CUSCO 01 | |
| 173 | Research Site | Lima | Peru | 41 | |
| 174 | Research Site | Lima | Peru | L27 | |
| 175 | Research Site | Lima | Peru | LIMA 1 | |
| 176 | Research Site | Lima | Peru | LIMA 21 | |
| 177 | Research Site | Lima | Peru | LIMA 29 | |
| 178 | Research Site | Lima | Peru | LIMA 32 | |
| 179 | Research Site | Lima | Peru | LIMA 33 | |
| 180 | Research Site | Lima | Peru | LIMA 41 | |
| 181 | Research Site | Bydgoszcz | Poland | 85-079 | |
| 182 | Research Site | Będzin | Poland | 42-500 | |
| 183 | Research Site | Chorzów | Poland | 41-500 | |
| 184 | Research Site | Gdańsk | Poland | 80-405 | |
| 185 | Research Site | Gdańsk | Poland | 80-546 | |
| 186 | Research Site | Grudziądz | Poland | 86-300 | |
| 187 | Research Site | Kielce | Poland | 25-734 | |
| 188 | Research Site | Kraków | Poland | 31-209 | |
| 189 | Research Site | Lubin | Poland | 59-300 | |
| 190 | Research Site | Lublin | Poland | 20-363 | |
| 191 | Research Site | Lublin | Poland | 20-468 | |
| 192 | Research Site | Mrozy | Poland | 05-320 | |
| 193 | Research Site | Olsztyn | Poland | 10-357 | |
| 194 | Research Site | Ostrowiec Świętokrzyski | Poland | 27-400 | |
| 195 | Research Site | Ostrów Wielkopolski | Poland | 63-400 | |
| 196 | Research Site | Oświęcim | Poland | 32-600 | |
| 197 | Research Site | Puławy | Poland | 24-100 | |
| 198 | Research Site | Racibórz | Poland | 47-400 | |
| 199 | Research Site | Skierniewice | Poland | 96-100 | |
| 200 | Research Site | Staszów | Poland | 28-200 | |
| 201 | Research Site | Warszawa | Poland | 01-138 | |
| 202 | Research Site | Wieluń | Poland | 98-300 | |
| 203 | Research Site | Wołomin | Poland | 05-200 | |
| 204 | Research Site | Wrocław | Poland | 50-220 | |
| 205 | Research Site | Wrocław | Poland | 51-162 | |
| 206 | Research Site | Zamość | Poland | 22-400 | |
| 207 | Research Site | Zgierz | Poland | 95-100 | |
| 208 | Research Site | Łódź | Poland | 90-153 | |
| 209 | Research Site | Humenne | Slovakia | 066 01 | |
| 210 | Research Site | Kezmarok | Slovakia | 060 01 | |
| 211 | Research Site | Presov | Slovakia | 08001 | |
| 212 | Research Site | Sabinov | Slovakia | ||
| 213 | Research Site | Topolcany | Slovakia | 955 01 | |
| 214 | Research Site | Alicante | Spain | 03004 | |
| 215 | Research Site | Badalona | Spain | 08916 | |
| 216 | Research Site | Hospitalet de Llobregat(Barcel | Spain | 08907 | |
| 217 | Research Site | Santander | Spain | 39008 | |
| 218 | Research Site | Valencia | Spain | 46015 | |
| 219 | Research Site | Changhua | Taiwan | 500 | |
| 220 | Research Site | Kaohsiung | Taiwan | ||
| 221 | Research Site | New-Taipei | Taiwan | 22056 | |
| 222 | Research Site | Taichung | Taiwan | 404 | |
| 223 | Research Site | Taipei | Taiwan | 100 | |
| 224 | Research Site | Taipei | Taiwan | 235 | |
| 225 | Research Site | Yilan | Taiwan | 260 | |
| 226 | Research Site | Chernivtsi | Ukraine | 58000 | |
| 227 | Research Site | Chernivtsi | Ukraine | 58001 | |
| 228 | Research Site | Ivano-Frankivsk | Ukraine | 76012 | |
| 229 | Research Site | Kharkiv | Ukraine | 61002 | |
| 230 | Research Site | Kharkiv | Ukraine | 61058 | |
| 231 | Research Site | Kharkiv | Ukraine | 61093 | |
| 232 | Research Site | Kyiv | Ukraine | 02125 | |
| 233 | Research Site | Lutsk | Ukraine | 43000 | |
| 234 | Research Site | Lviv | Ukraine | 79066 | |
| 235 | Research Site | Odesa | Ukraine | 65025 | |
| 236 | Research Site | Vinnytsia | Ukraine | 21001 | |
| 237 | Research Site | Zaporizhzhya | Ukraine | 69063 | |
| 238 | Research Site | Zaporizhzhya | Ukraine | 69065 | |
| 239 | Research Site | Can Tho | Vietnam | 900000 | |
| 240 | Research Site | Ha Noi | Vietnam | 100000 | |
| 241 | Research Site | Hanoi | Vietnam | 100000 | |
| 242 | Research Site | Ho Chi Minh | Vietnam | 700000 | |
| 243 | Research Site | Hochiminh | Vietnam |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Reynold A Panettieri, M.D., University of Pennsylvania Perelman School of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02161757
Other Study ID Numbers:
- D2210C00007
First Posted:
Jun 12, 2014
Last Update Posted:
Aug 28, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | First patient enrolled: 13 Jun 2014; Week 52 cut-off: 28 Feb 2017; Last Patient Last Visit Week 72: 18 Jul 2017. Study performed at 254 sites in 14 countries. Patients were maintained on currently prescribed inhaled corticosteroid long-acting β2-agonist therapy + any additional maintenance asthma controller medications throughout the study period. |
|---|---|
| Pre-assignment Detail | 2248 patients signed informed consent, 1669 entered screening/run-in period, 1207 patients were randomised to receive treatment with tralokinumab 300 milligrams (mg), or placebo, every 2 weeks (Q2W) or every 4 weeks (Q4W). Of the 1207 patients randomised, 1202 received investigational product (IP). |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Period Title: Randomised Through Start Treatment | |||
| STARTED | 401 | 406 | 400 |
| COMPLETED | 398 | 404 | 400 |
| NOT COMPLETED | 3 | 2 | 0 |
| Period Title: Randomised Through Start Treatment | |||
| STARTED | 398 | 404 | 400 |
| Completed Treatment for Week 52 Cut-off | 332 | 355 | 360 |
| COMPLETED | 341 | 361 | 361 |
| NOT COMPLETED | 57 | 43 | 39 |
Baseline Characteristics
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. | Total of all reporting groups |
| Overall Participants | 398 | 404 | 400 | 1202 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
49.4
(14.3)
|
51.1
(13.9)
|
51.4
(14.3)
|
50.6
(14.2)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
252
63.3%
|
281
69.6%
|
265
66.3%
|
798
66.4%
|
| Male |
146
36.7%
|
123
30.4%
|
135
33.8%
|
404
33.6%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
21
5.3%
|
22
5.4%
|
25
6.3%
|
68
5.7%
|
| Asian |
53
13.3%
|
55
13.6%
|
55
13.8%
|
163
13.6%
|
| Native Hawaiian or Other Pacific Islander |
1
0.3%
|
0
0%
|
0
0%
|
1
0.1%
|
| Black or African American |
21
5.3%
|
16
4%
|
14
3.5%
|
51
4.2%
|
| White |
285
71.6%
|
297
73.5%
|
288
72%
|
870
72.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
17
4.3%
|
14
3.5%
|
18
4.5%
|
49
4.1%
|
Outcome Measures
| Title | Annualised Asthma Exacerbation Rate (AAER) up to Week 52 |
|---|---|
| Description | Asthma exacerbation was defined as a worsening of asthma that led to any of the following: Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for <24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids (see above). An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma. AAER = number of exacerbations*365.25 / (follow-up date - date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks). AAER in the tralokinumab group was compared to that seen in the placebo group up to Week 52 using a negative binomial model; rate ratios and rate reductions are both presented for comparative statistical analyses. |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Number (95% Confidence Interval) [Events/year] |
0.56
|
0.54
|
0.60
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of AAER (rate ratio): Tralo 300 mg Q2W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo. | |
| Statistical Test of Hypothesis | p-Value | 0.5859 |
| Comments | ||
| Method | Negative binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.93 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of AAER (rate ratio): Tralo 300 mg Q4W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo. | |
| Statistical Test of Hypothesis | p-Value | 0.4406 |
| Comments | ||
| Method | Negative binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.90 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 1.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of AAER (rate reduction): Tralo 300 mg Q2W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo. | |
| Statistical Test of Hypothesis | p-Value | 0.5859 |
| Comments | ||
| Method | Negative binominal | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate reduction |
| Estimated Value | 7.01 | |
| Confidence Interval |
(2-Sided) 95% -20.76 to 28.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of AAER (rate reduction): Tralo 300 mg Q4W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo. | |
| Statistical Test of Hypothesis | p-Value | 0.4406 |
| Comments | ||
| Method | Negative binominal | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate reduction |
| Estimated Value | 9.76 | |
| Confidence Interval |
(2-Sided) 95% -17.16 to 30.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study. | |
| Title | Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1) |
|---|---|
| Description | Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorised delegate according to American Thoracic Society/European Respiratory Society guidelines. The mean percent change from baseline in pre-BD FEV1 at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 357 | 373 | 363 |
| Mean (Standard Deviation) [Percent change from baseline] |
16.366
(27.349)
|
12.099
(26.253)
|
10.136
(24.206)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of percent change from baseline in pre-dose/pre-BD FEV1 at Week 52: Tralo 300 mg Q2W vs placebo. Restricted maximum likelihood (REML) based repeated measures analysis performed on patients with a baseline pre-dose/pre-BD FEV1 assessment. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square (LS) Mean difference |
| Estimated Value | 6.03 | |
| Confidence Interval |
(2-Sided) 95% 2.34 to 9.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of percent change from baseline in pre-dose/pre-BD FEV1 at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis performed on patients with a baseline pre-dose/pre-BD FEV1 assessment. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 2.10 | |
| Confidence Interval |
(2-Sided) 95% -1.58 to 5.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means) |
|---|---|
| Description | Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary. Symptoms were recorded using a 4-point response scale, which ranged from 0 to 3, where 0 indicated no asthma symptoms. Asthma symptom daytime score (recorded in the evening), night-time score (recorded in the morning), and total score were calculated separately. The daily asthma symptom total score was calculated by taking the sum of the night-time and daytime asthma symptom scores recorded each day, ranging from 0 to 6. A lower symptom score indicated a better outcome. The change from baseline in bi-weekly mean daily asthma symptom total score is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 313 | 313 | 312 |
| Mean (Standard Deviation) [Scores on a scale] |
-1.09
(1.22)
|
-1.00
(1.11)
|
-1.03
(1.13)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in total asthma symptom score at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.23 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline asthma symptom score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in total asthma symptom score at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.15 to 0.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline asthma symptom score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score |
|---|---|
| Description | The AQLQ(S)+12 is a questionnaire that measures health-related quality of life for patients with asthma aged 12 and older. The questionnaire comprises 32 questions and has 4 separate domains (asthma symptoms, activity limitations, emotional function and environmental stimuli). Patients were asked to recall their experiences during the previous 2 weeks and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The total score was calculated as the mean response to all questions, ranging from 1 (severe impairment) to 7 (no impairment). Individual AQLQ(S)+12 total score changes of ≥0.5 were considered to be clinically meaningful. The mean change from baseline in AQLQ(S)+12 score at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 304 | 321 | 315 |
| Mean (Standard Deviation) [Scores on a scale] |
1.18
(1.17)
|
1.16
(1.14)
|
1.03
(1.24)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of change in mean score from baseline for AQLQ(S)+12 at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline AQLQ(S)+12 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of change in mean score from baseline for AQLQ(S)+12 at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.03 to 0.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline AQLQ(S)+12 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score |
|---|---|
| Description | The ACQ-6 questionnaire is a shortened version of the ACQ (omitting FEV1 measurement) that assesses asthma symptoms (night-time awakenings, symptoms on waking, activity limitation, dyspnoea, wheezing) and rescue short-acting β2-agonists medication use during the past week. Questions were weighted equally and scored on a 7-point scale from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma and a score >1.5 indicates not well-controlled asthma. Individual changes of at least 0.5 were considered to be clinically meaningful. The mean change from baseline in ACQ-6 score at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 324 | 344 | 329 |
| Mean (Standard Deviation) [Scores on a scale] |
-1.19
(1.06)
|
-1.12
(1.03)
|
-1.02
(1.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of change in mean score from baseline for ACQ-6 at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.29 to -0.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline ACQ-6 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of change in mean score from baseline for ACQ-6 at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline ACQ-6 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | AAER Associated With an ER/UC Visit, or a Hospitalisation up to Week 52 |
|---|---|
| Description | The annual rate of exacerbations associated with an ER/UC visit or hospitalisation up to Week 52 are presented for non-adjudicated data (i.e. events assessed by the Investigator and recorded in the electronic case report form). AAER = Number of Exacerbations*365.25 / (Follow-up date - Date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks). |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Number (95% Confidence Interval) [Events/year] |
0.04
|
0.06
|
0.07
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of AAER associated with an ER/UC visit or hospitalisation: Tralo 300 mg Q2W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0369 |
| Comments | ||
| Method | Negative binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% 0.30 to 0.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations resulting in hospitalisation or ER treatment (yes/no) in the year before the study. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of AAER associated with an ER/UC visit or hospitalisation: Tralo 300 mg Q4W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3603 |
| Comments | ||
| Method | Negative binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 1.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations resulting in hospitalisation or ER treatment (yes/no) in the year before the study. | |
| Title | Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at Week 52 |
|---|---|
| Description | The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a VAS, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. The mean change from baseline in EQ-5D-5L VAS scores at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 306 | 319 | 324 |
| Mean (Standard Deviation) [Scores on a scale] |
10.68
(20.33)
|
9.00
(18.99)
|
10.06
(18.92)
|
| Title | Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means) |
|---|---|
| Description | Salbutamol, albuterol or levalbuterol were used as rescue medication during the study in the event of a worsening of asthma symptoms. Rescue medication use was measured by the bi-weekly mean number of inhalations (puffs) per day, calculated as: total morning puffs + total evening puffs + 2*(total morning nebuliser use + total evening nebuliser use)/ total number of days with data in bi-weekly period. The change from baseline in bi-weekly mean total asthma rescue medication use at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 313 | 313 | 312 |
| Mean (Standard Deviation) [Puffs/day] |
-2.18
(3.46)
|
-2.15
(3.69)
|
-2.04
(3.84)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in rescue medication use at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 0.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline rescue medication use, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in rescue medication use at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.56 to 0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline rescue medication use, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at Week 52 |
|---|---|
| Description | Home PEF testing was performed by the patient using an electronic, hand-held spirometer (peak flow meter) and was performed in the morning upon awakening (prior to taking their morning asthma controller) and in the evening at bedtime (prior to taking their evening asthma controller). The mean change from baseline in home PEF values at Week 52 are presented separately for morning and evening. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 321 | 326 | 329 |
| Morning PEF |
12.95
(85.66)
|
7.55
(74.97)
|
5.23
(74.10)
|
| Evening PEF |
8.89
(83.02)
|
0.68
(73.19)
|
-0.28
(76.05)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in morning PEF at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 6.25 | |
| Confidence Interval |
(2-Sided) 95% -3.53 to 16.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline PEF (morning), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in morning PEF at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 1.77 | |
| Confidence Interval |
(2-Sided) 95% -7.99 to 11.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline PEF (morning), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in evening PEF at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 7.14 | |
| Confidence Interval |
(2-Sided) 95% -2.60 to 16.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline PEF (evening), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in evening PEF at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 0.61 | |
| Confidence Interval |
(2-Sided) 95% -9.13 to 10.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline PEF (evening), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage]) |
|---|---|
| Description | The patient captured night-time awakenings (yes/no) and the use of rescue medication during these awakenings (yes/no) each morning in the Asthma Daily Diary. Night-time awakenings (percentage) was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data. The change from baseline in bi-weekly means (percentage) night-time awakenings due to asthma requiring rescue medication use at Week 52 is presented. |
| Time Frame | Baseline (Week 0) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 346 | 357 | 357 |
| Mean (Standard Deviation) [Percentage of nights with awakenings] |
-37.63
(37.27)
|
-35.17
(37.49)
|
-36.00
(36.69)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in number (%) of awakenings at Week 52: Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -1.80 | |
| Confidence Interval |
(2-Sided) 95% -5.29 to 1.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline number (%) of awakenings, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of mean change from baseline in number (%) of awakenings at Week 52: Tralo 300 mg Q4W vs placebo. REML based repeated measures analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -2.36 | |
| Confidence Interval |
(2-Sided) 95% -5.84 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Fixed categorical effects of baseline number (%) of awakenings, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate. | |
| Title | Number of Patients With ≥1 Asthma Exacerbation up to Week 52 |
|---|---|
| Description | The number of patients with ≥1 asthma exacerbation up to Week 52 is presented. |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Count of Participants [Participants] |
128
32.2%
|
124
30.7%
|
133
33.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q2W, Placebo |
|---|---|---|
| Comments | Comparison of number of patients with ≥ 1 asthma exacerbations up to Week 52: Tralo 300 mg Q2W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.732 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.95 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 1.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimate of each odds ratio was obtained from two separate models, from a Cochran-Mantel-Haenszel test controlling for geographical region, age group and periostin group at baseline. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tralo 300 mg Q4W, Placebo |
|---|---|---|
| Comments | Comparison of number of patients with ≥ 1 asthma exacerbations up to Week 52: Tralo 300 mg Q4W vs placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.421 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimate of each odds ratio was obtained from two separate models, from a Cochran-Mantel-Haenszel test controlling for geographical region, age group and periostin group at baseline. | |
| Title | Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss at Week 52 |
|---|---|
| Description | The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for productivity loss are presented separately for those currently employed and for those currently in school and are expressed as mean productivity loss (percentage) at Week 52, with higher numbers indicating less productivity. Work Productivity Loss = {Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]}*100 (Absenteeism = Q2/(Q2+Q4)*100; Presenteeism = (Q5/10)*100). Class Productivity Loss = {Q7/(Q7+Q8) + [(1-Q7/(Q7+Q8))x(Q9/10)]}*100 (Absenteeism = Q7/ (Q7+Q8)*100; Presenteeism = (Q9/10)*100). Note: QX refers to response to question number X on WPAI+CIQ questionnaire. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoint of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 123 | 130 | 137 |
| Productivity loss - currently employed |
27.71
(24.06)
|
28.48
(25.11)
|
31.25
(25.34)
|
| Productivity loss - currently in school |
33.13
(28.03)
|
31.79
(34.28)
|
32.31
(28.46)
|
| Title | WPAI+CIQ: Activity Impairment at Week 52 |
|---|---|
| Description | The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for activity impairment are presented separately for those currently employed and for those currently in school and are expressed as mean impairment percentages at Week 52, with higher numbers indicating greater impairment. Activity impairment = (Q10/10)*100. Note: QX refers to response to question number X on WPAI+CIQ questionnaire. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoint of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 134 | 135 | 146 |
| Activity Impairment - currently employed |
23.25
(21.31)
|
23.53
(22.57)
|
27.01
(23.21)
|
| Activity Impairment - currently in school |
29.29
(20.56)
|
27.50
(29.55)
|
28.95
(23.07)
|
| Title | Asthma-related Healthcare Encounters by Type up to Week 52 |
|---|---|
| Description | Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of times the healthcare encounter occurred was calculated across all patients for each of the following categories: Ambulance transport, Emergency room visits, Unscheduled outpatient visits (visit to specialist and/or visit to primary healthcare physician and/or other healthcare visit), Home visits (home visit, physician and/or other healthcare professional), Telephone calls (telephone calls to physician and/or nurse), and Advanced pulmonary function test. |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Ambulance transport |
5
|
15
|
16
|
| Emergency room visits |
59
|
87
|
64
|
| Unscheduled outpatient visits |
1750
|
1786
|
1705
|
| Home visits |
21
|
5
|
6
|
| Telephone calls |
515
|
463
|
198
|
| Advanced pulmonary function test |
84
|
70
|
67
|
| Title | Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations |
|---|---|
| Description | Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of days spent in hospital was calculated across all patients for the following healthcare encounter category: • Hospitalisations (hospitalisations, intensive care and/or general care). |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Number [Days] |
270
|
345
|
482
|
| Title | Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry |
|---|---|
| Description | Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of assessments was calculated across all patients for the following healthcare encounter category: • Spirometry. |
| Time Frame | Baseline (Week 0) up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised patients who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 398 | 404 | 400 |
| Number [Assessments] |
489
|
520
|
502
|
| Title | Serum Trough Concentration (Ctrough) of Tralokinumab During the Study Period up to Week 72 |
|---|---|
| Description | To evaluate the pharmacokinetics (PK), pre-dose blood samples were collected at each visit and tralokinumab concentrations in serum were determined. Mean Ctrough concentrations are presented at each indicated visit up to Week 72. |
| Time Frame | Blood samples were collected pre-dose at Baseline (Week 0), and at Week 4, Week 8, Week 26, Week 52 and Week 72 (follow-up) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients in the FAS who received tralokinumab and who had PK blood samples were included in the PK analysis set. Only patients with data available at the timepoints of testing were included in the analysis. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W |
|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 394 | 401 |
| Baseline |
NA
(NA)
|
NA
(NA)
|
| Week 4 |
34.690
(199.269)
|
13.151
(188.026)
|
| Week 8 |
55.262
(159.824)
|
19.243
(112.830)
|
| Week 26 |
52.766
(257.341)
|
30.305
(255.039)
|
| Week 52 |
37.074
(675.764)
|
14.290
(437.472)
|
| Week 72 (follow-up) |
0.419
(238.749)
|
0.172
(171.973)
|
| Title | Number of Patients Positive for Anti-drug Antibodies (ADAs) |
|---|---|
| Description | ADA assessments performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for neutralising antibodies (nAb). ADA prevalence defined as proportion of study population with drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) defined as sum of treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive defined as having ≥1 post-baseline ADA positive assessment and not fulfilling conditions of persistently positive. Treatment-boosted ADA defined as baseline positive ADA titer boosted to a 4-fold or higher level following drug administration. In some category titles 'positive' is denoted by 'pos'. |
| Time Frame | Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ADA evaluable population included all patients in the safety analysis set (i.e. those who had received any IP) who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. |
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo |
|---|---|---|---|
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. |
| Measure Participants | 373 | 382 | 374 |
| ADA prevalence |
7
1.8%
|
7
1.7%
|
9
2.3%
|
| ADA incidence |
3
0.8%
|
2
0.5%
|
3
0.8%
|
| ADA positive at baseline |
4
1%
|
5
1.2%
|
7
1.8%
|
| ADA positive post-baseline |
3
0.8%
|
3
0.7%
|
8
2%
|
| ADA pos post-baseline and pos at baseline |
0
0%
|
1
0.2%
|
6
1.5%
|
| ADA pos post-baseline and not detected at baseline |
3
0.8%
|
2
0.5%
|
2
0.5%
|
| ADA not detected post-baseline and pos at baseline |
4
1%
|
4
1%
|
1
0.3%
|
| Persistent Positive |
2
0.5%
|
2
0.5%
|
7
1.8%
|
| Transient Positive |
1
0.3%
|
1
0.2%
|
1
0.3%
|
| Treatment-boosted ADA |
0
0%
|
0
0%
|
1
0.3%
|
| nAB positive at any visit |
5
1.3%
|
5
1.2%
|
4
1%
|
Adverse Events
| Time Frame | Serious and Other (non-serious) adverse event (AE) data reported for the treatment period, from baseline (Week 0) to end of treatment (Week 52). All-Cause mortality is reported for the overall study period (including the extended follow-up period), up to Week 72. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent AEs were defined with an onset date ≥ the first day of IP and ≤ (the last day of IP + dosing frequency). 'Dosing frequency' was 2 or 4 weeks depending on whether patients were randomised to Q2W or Q4W dosing regimens. Patient population was safety analysis set which included all patients who received at least one dose of any IP. | |||||
| Arm/Group Title | Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo | |||
| Arm/Group Description | Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Follow-up visits were conducted at Weeks 56 and 72. | Tralokinumab 300 mg administered subcutaneously Q4W over a 52-week treatment period (up to 13 doses). Follow-up visits were conducted at Weeks 56 and 72. | Placebo was administered subcutaneously over a 52-week treatment period. The placebo treatment group is a pooled treatment group (placebo Q2W + placebo Q4W) where the 2 placebo cohorts were given weights proportional to the number of patients in each cohort. Follow-up visits were conducted at Weeks 56 and 72. | |||
All Cause Mortality |
||||||
| Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/398 (0.5%) | 1/404 (0.2%) | 1/400 (0.3%) | |||
Serious Adverse Events |
||||||
| Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/398 (10.1%) | 39/404 (9.7%) | 48/400 (12%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Lymphadenopathy | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Cardiac disorders | ||||||
| Acute myocardial infarction | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 2/400 (0.5%) | 2 |
| Angina pectoris | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Angina unstable | 1/398 (0.3%) | 2 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Arrhythmia | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Atrial fibrillation | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Cardiac failure | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Cardiac failure acute | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Cardiac failure congestive | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Coronary artery disease | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Myocardial infarction | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Pericarditis | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Sinus node dysfunction | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 2 |
| Supraventricular tachycardia | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Eye disorders | ||||||
| Cataract | 0/398 (0%) | 0 | 2/404 (0.5%) | 3 | 1/400 (0.3%) | 1 |
| Retinal detachment | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Diarrhoea | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Erosive duodenitis | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Swollen tongue | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Umbilical hernia | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 1/398 (0.3%) | 2 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Cholelithiasis | 2/398 (0.5%) | 2 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Immune system disorders | ||||||
| Eosinophilic granulomatosis with polyangiitis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Infections and infestations | ||||||
| Chronic sinusitis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Peritonitis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Appendicitis | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Bronchitis | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Diarrhoea infectious | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Erysipelas | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Gastroenteritis | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Herpes zoster | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Pneumonia | 3/398 (0.8%) | 4 | 3/404 (0.7%) | 3 | 4/400 (1%) | 6 |
| Pneumonia viral | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Pyelonephritis | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Pyelonephritis acute | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 1/400 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Facial bones fracture | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Fall | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Humerus fracture | 2/398 (0.5%) | 2 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Joint dislocation | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Limb injury | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Femur fracture | 1/398 (0.3%) | 1 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Laceration | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Meniscus injury | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Post procedural complication | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Post-traumatic pain | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Investigations | ||||||
| Blood pressure increased | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dyslipidaemia | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Hypokalaemia | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Hypovolaemia | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Osteoarthritis | 0/398 (0%) | 0 | 2/404 (0.5%) | 2 | 0/400 (0%) | 0 |
| Ankylosing spondylitis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Arthralgia | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Osteochondrosis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Rheumatoid arthritis | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Spinal pain | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Synovitis | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Trigger finger | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 1/398 (0.3%) | 1 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Cervix carcinoma | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Uterine cancer | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Nervous system disorders | ||||||
| Cerebrovascular disorder | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Radiculopathy | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Transient ischaemic attack | 2/398 (0.5%) | 2 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Carpal tunnel syndrome | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Cerebral haemorrhage | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Dizziness | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Haemorrhagic stroke | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Ischaemic stroke | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Vascular encephalopathy | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Vertebrobasilar insufficiency | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Psychiatric disorders | ||||||
| Depression | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Hallucination | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Ovarian cyst | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 0/400 (0%) | 0 |
| Metrorrhagia | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Prostatitis | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 12/398 (3%) | 15 | 19/404 (4.7%) | 23 | 25/400 (6.3%) | 39 |
| Atelectasis | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Dyspnoea | 0/398 (0%) | 0 | 0/404 (0%) | 0 | 1/400 (0.3%) | 1 |
| Pharyngeal oedema | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Pulmonary embolism | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Angioedema | 1/398 (0.3%) | 1 | 0/404 (0%) | 0 | 0/400 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 0/398 (0%) | 0 | 1/404 (0.2%) | 1 | 1/400 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Tralo 300 mg Q2W | Tralo 300 mg Q4W | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 134/398 (33.7%) | 145/404 (35.9%) | 107/400 (26.8%) | |||
| General disorders | ||||||
| Injection site erythema | 24/398 (6%) | 58 | 12/404 (3%) | 29 | 0/400 (0%) | 0 |
| Infections and infestations | ||||||
| Bronchitis | 20/398 (5%) | 29 | 23/404 (5.7%) | 27 | 18/400 (4.5%) | 24 |
| Upper respiratory tract infection | 26/398 (6.5%) | 40 | 48/404 (11.9%) | 61 | 36/400 (9%) | 73 |
| Viral upper respiratory tract infection | 44/398 (11.1%) | 62 | 48/404 (11.9%) | 67 | 37/400 (9.3%) | 55 |
| Nervous system disorders | ||||||
| Headache | 23/398 (5.8%) | 35 | 31/404 (7.7%) | 42 | 17/400 (4.3%) | 28 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 35/398 (8.8%) | 55 | 33/404 (8.2%) | 43 | 28/400 (7%) | 45 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Global Clinical Lead |
|---|---|
| Organization | AstraZeneca |
| Phone | +1 301-398-0582 |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02161757
Other Study ID Numbers:
- D2210C00007
First Posted:
Jun 12, 2014
Last Update Posted:
Aug 28, 2018
Last Verified:
Jul 1, 2018