A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma

Uncontrolled Asthma Clinical Trial

— STRATOS2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02194699
• Other study ID #: D2210C00008
• Status: Completed
• Phase: Phase 3
• Start date: October 30, 2014
• Est. completion date: September 21, 2017

Study information

• Verified date: April 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 770 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 856
• Est. completion date: September 21, 2017
• Est. primary completion date: May 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 12 -75

2. Documented physician-diagnosed asthma.

3. Documented treatment with ICS at a total daily dose corresponding to =500µg fluticasone propionate dry powder formulation equivalents) and a LABA

4. Morning pre-BD FEV1 value of =40 and <80% value (<90% for patients 12 to 17 years of age) of their PNV.

5. Post-BD reversibility of =12% and =200 mL in FEV1

6. ACQ-6 score =1.5

Exclusion Criteria:

1. Pulmonary disease other than asthma

2. History of anaphylaxis following any biologic therapy

3. Hepatitis B, C or HIV

4. Pregnant or breastfeeding

5. History of cancer

6. Current tobacco smoking or a history of tobacco smoking for = 10 pack-years

7. Previous receipt of tralokinumab

Related Conditions & MeSH terms

• Asthma
• Uncontrolled Asthma

Intervention

Biological:
• Experimental: Tralokinumab
Tralokinumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Windsor	Ontario
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talcahuano
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Praha
Czechia	Research Site	Praha 10 - Strasnice
Czechia	Research Site	Rokycany
Czechia	Research Site	Teplice
Italy	Research Site	Catania
Italy	Research Site	Genova
Italy	Research Site	Legnago
Italy	Research Site	Messina
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Pisa
Italy	Research Site	Salerno
Italy	Research Site	Verona
Japan	Research Site	Asahi-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukui-shi
Japan	Research Site	Fukushima-shi
Japan	Research Site	Habikino-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Izumo-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kanazawa
Japan	Research Site	Kanuma-shi
Japan	Research Site	Kasuga-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kochi-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Matsue-shi
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Morioka-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sasebo-shi
Japan	Research Site	Seto-shi
Japan	Research Site	Shibuya-ku
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sumida-ku
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Touon-shi
Japan	Research Site	Toyama-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Tsukubo-gun
Japan	Research Site	Uozu-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Villahermosa
Philippines	Research Site	Caloocan City
Philippines	Research Site	Iloilo City
Philippines	Research Site	Lipa City
Philippines	Research Site	Pasig City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Philippines	Research Site	San Fernando
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Petrozavodsk
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Saint - Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Boksburg North
South Africa	Research Site	Durban
South Africa	Research Site	Mount Edgecombe
South Africa	Research Site	Mowbray
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Stanger
Taiwan	Research Site	Kaohsiung Hsien
Taiwan	Research Site	Keelung
Taiwan	Research Site	New-Taipei
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kremenchuk
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Sumy
Ukraine	Research Site	Sumy
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Chertsey
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Sidcup
United Kingdom	Research Site	Wishaw
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Arlington	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Baytown	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bronx	New York
United States	Research Site	Bronx	New York
United States	Research Site	Buena Park	California
United States	Research Site	Burlington	North Carolina
United States	Research Site	Canton	Ohio
United States	Research Site	Celebration	Florida
United States	Research Site	Centennial	Colorado
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Georgia
United States	Research Site	DeLand	Florida
United States	Research Site	Eagle	Idaho
United States	Research Site	Encinitas	California
United States	Research Site	Evergreen Park	Illinois
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Frisco	Texas
United States	Research Site	Gainesville	Georgia
United States	Research Site	Gainesville	Florida
United States	Research Site	Greenfield	Wisconsin
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Hialeah	Florida
United States	Research Site	Hoover	Alabama
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Kenilworth	Illinois
United States	Research Site	Kingwood	Texas
United States	Research Site	Lakewood	California
United States	Research Site	Larchmont	New York
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Lomita	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New Port Richey	Florida
United States	Research Site	Northfield	New Jersey
United States	Research Site	Northridge	California
United States	Research Site	Ocean City	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orem	Utah
United States	Research Site	Orlando	Florida
United States	Research Site	Palmdale	California
United States	Research Site	Palmetto Bay	Florida
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Reno	Nevada
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Roseville	California
United States	Research Site	Sacramento	California
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Savannah	Georgia
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Tampa	Florida
United States	Research Site	Teaneck	New Jersey
United States	Research Site	Thousand Oaks	California
United States	Research Site	Toms River	New Jersey
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Ventura	California
United States	Research Site	Verona	New Jersey
United States	Research Site	Walnut Creek	California
United States	Research Site	Wappingers Falls	New York
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Czechia,  Italy,  Japan,  Mexico,  Philippines,  Russian Federation,  South Africa,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualised Asthma Exacerbation Rate (AAER) 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.	Baseline (Week 0) up to Week 52
Secondary	Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1)	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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means)	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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score	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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score	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 ß2-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.	Baseline (Week 0) and Week 52
Secondary	AAER Associated With an ER/UC Visit, or a Hospitalisation 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).	Baseline (Week 0) up to Week 52
Secondary	Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at 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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means)	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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at 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.	Baseline (Week 0) and Week 52
Secondary	Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage])	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.	Baseline (Week 0) and Week 52
Secondary	Number of Patients With =1 Asthma Exacerbation up to Week 52	The number of patients with =1 asthma exacerbation up to Week 52 is presented.	Baseline (Week 0) up to Week 52
Secondary	Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss 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.	At Week 52
Secondary	WPAI+CIQ: Activity Impairment 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.	At Week 52
Secondary	Asthma-related Healthcare Encounters by Type 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.	Baseline (Week 0) up to Week 52
Secondary	Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations	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).	Baseline (Week 0) up to Week 52
Secondary	Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry	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.	Baseline (Week 0) up to Week 52
Secondary	Serum Trough Concentration (Ctrough) of Tralokinumab During the Treatment Period up to Week 72	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.	Blood samples were collected pre-dose at Baseline (Week 0), and at Week 2, Week 8, Week 26, Week 56 (follow-up) and Week 72 (follow-up)
Secondary	Incidence Rate of Positive Anti-drug Antibodies (ADAs) Including the Characterization of Their Neutralizing Potential	Assessments of ADA were performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for the presence of neutralising antibodies (nAb). ADA prevalence was defined as proportion of the study population having drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) was defined as the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive was 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 was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration. Note: 'positive' is denoted by 'pos' in some category titles.	Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)