Open Label, Long-term Study Evaluating Safety and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Dermatitis Atopic Clinical Trial

— ATLANTIS  

Official title:

An Open-Label Multinational, Multicenter Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05769777
• Other study ID #: LTS17789
• Secondary ID: U1111-1280-60802
• Status: Recruiting
• Phase: Phase 2
• Start date: April 3, 2023
• Est. completion date: October 9, 2028

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single group, 1-arm, long-term safety study for treatment of participants with moderate to severe atopic dermatitis (AD). The purpose of this study is to characterize the long-term safety and efficacy of amlitelimab in treated participants with age ≥12 years old with moderate to severe AD. The study duration per participant will be up to 180 weeks, including: - A screening period of up to 2 to 4 weeks - An open label treatment period of up to 160 weeks (approximately 3 years) - A post-treatment safety follow-up period of at least 20 weeks after the last dose administration The planned number of visits will be 26 visits.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 901
• Est. completion date: October 9, 2028
• Est. primary completion date: October 9, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Participant must be at least 12 years of age inclusive, at the time of signing the informed consent.
• Participants must have AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer at baseline.
• Participant must have documented history within 6 months prior to screening visit, of either inadequate response or inadvisability of topical treatments.
• Eczema Area Severity Index (EASI) of 16 or higher at baseline visit/Visit 2.
• Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 3 or 4 at baseline visit/Visit 2.
• AD involvement of 10% or more of body surface area (BSA) at baseline visit/Visit 2.
• Weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) of = 4 at baseline visit/Visit 2.
• Able and willing to comply with requested study visits and procedures.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participants must not be pregnant or breastfeeding.

Exclusion Criteria:

• Skin co-morbidity that would adversely affect the ability to undertake AD assessments as per investigator's judgement
• Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
• Any malignancies or history of malignancies prior to baseline (except for non-melanoma skin cancer that has been excised and completely cured for more than 5 years prior to baseline).
• History of solid organ or stem cell transplant.
• Any pre-planned major elective surgery known about at baseline that in the opinion of the investigator would necessitate that IMP be permanently discontinued or require more than three doses to be missed.
• Severe concomitant illness that would in the Investigator's opinion inhibit the participant's participation in the study.
• Any medical or psychiatric condition which, in the opinion of the Investigator may present an unreasonable risk to the study participants as a result of his/her participation in this clinical study, may make participant's participation unreliable, or may interfere with study assessments.
• Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to baseline (1 week in the event of superficial skin infections); and any infection (including confirmed Covid-19 infection at screening or baseline) which as per Investigator's opinion precludes the participant's participation in the study.
• Treatment with live (attenuated) vaccines within 12 weeks prior to baseline; failure to complete non-live immunizations required by local regulation (eg, vaccination for COVID-19) at least 14 days prior to baseline.
• Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit.
• Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at the screening visit.
• Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, non-TB mycobacterial infection, or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening.
• In the Investigator's opinion, any clinically significant laboratory results from the clinical chemistry, haematology or urinalysis tests at the screening visit.
• In the Investigator's opinion, any significant abnormality on 12-lead electrocardiogram (ECG) at the screening visit that could be suggestive of an unstable or underlying cardio-vascular condition that could preclude the participant's participation in the study.
• History of hypersensitivity or allergy to any of the excipients or IMP or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis Atopic
• Dermatitis, Atopic

Intervention

Drug:
• Amlitelimab
Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous (SC)

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Argentina	Investigational Site Number : 0320004	Buenos Aires
Argentina	Investigational Site Number : 0320005	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320008	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320009	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320002	Ciudad Autonoma Buenos Aires
Argentina	Investigational Site Number : 0320003	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Investigational Site Number : 0320006	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320007	Rosario	Santa Fe
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre Site Number : 0760005	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP) Site Number : 0760008	Ribeirao Preto	São Paulo
Brazil	IDERJ - Instituto de Dermatologia e Estética do Brasil Ltda Site Number : 0760004	Rio de Janeiro
Brazil	Instituto Bahiano de Imunoterapia - IBIS Site Number : 0760002	Salvador	Bahia
Brazil	FUNDACAO DO ABC - FACULDADE DE MEDICINA DO ABC (FMABC) Site Number : 0760001	Santo Andre	São Paulo
Brazil	Hospital de Base Sao Jose do Rio Preto Site Number : 0760003	Sao Jose do Rio Preto	São Paulo
Brazil	Clinica de Alergia Martti Antila Site Number : 0760006	Sorocaba	São Paulo
Canada	Investigational Site Number : 1240001	Calgary	Alberta
Canada	Investigational Site Number : 1240009	Etobicoke	Ontario
Canada	Investigational Site Number : 1240008	Mississauga	Ontario
Canada	Investigational Site Number : 1240002	Montreal	Quebec
Canada	Investigational Site Number : 1240011	Oakville	Ontario
Canada	Investigational Site Number : 1240004	Peterborough	Ontario
Canada	Investigational Site Number : 1240006	Quebec
Canada	Investigational Site Number : 1240010	Quebec
Canada	Investigational Site Number : 1240003	Richmond Hill
Canada	Investigational Site Number : 1240012	Toronto	Ontario
Chile	Investigational Site Number : 1520009	Osorno	Los Lagos
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520008	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520010	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520004	Valdivia	Los Ríos
China	Investigational Site Number : 1560014	Chengdu
China	Investigational Site Number : 1560013	Jingzhou
China	Investigational Site Number : 1560001	Shanghai
Czechia	Investigational Site Number : 2032105	Novy Jicin
Czechia	Investigational Site Number : 2032104	Ostrava
Czechia	Investigational Site Number : 2030003	Praha 10
Czechia	Investigational Site Number : 2032102	Praha 10
Czechia	Investigational Site Number : 2030006	Praha 6
Czechia	Investigational Site Number : 2030007	Praha 8
Denmark	Investigational Site Number : 2080001	Aarhus
France	Investigational Site Number : 2500004	Creteil
France	Investigational Site Number : 2500001	Lille
France	Investigational Site Number : 2500005	Marseille
France	Investigational Site Number : 2500003	Paris
France	Investigational Site Number : 2500006	Pierre Benite
France	Investigational Site Number : 2500002	Toulouse
Germany	Investigational Site Number : 2760009	Bad Bentheim
Germany	Investigational Site Number : 2762203	Berlin
Germany	Investigational Site Number : 2762201	Münster
Germany	Investigational Site Number : 2760010	Osnabrück
India	Investigational Site Number : 3560007	Bikaner
India	Investigational Site Number : 3560002	Nashik
India	Investigational Site Number : 3560008	Surat
Italy	Investigational Site Number : 3800005	Brescia
Italy	Investigational Site Number : 3800003	Milano	Lombardia
Italy	Investigational Site Number : 3800002	Napoli
Italy	Investigational Site Number : 3800004	Napoli
Italy	Investigational Site Number : 3800006	Roma
Italy	Investigational Site Number : 3800007	Roma
Japan	Investigational Site Number : 3923114	Obihiro-Shi	Hokkaido
Japan	Investigational Site Number : 3923110	Sakai-shi	Osaka
Japan	Investigational Site Number : 3923106	Shimotsuga-gun	Tochigi
Japan	Investigational Site Number : 3920001	Tachikawa-shi	Tokyo
Japan	Investigational Site Number : 3923113	Yokohama-Shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100002	Ansan-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100001	Seoul
Korea, Republic of	Investigational Site Number : 4100006	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100003	Yangsan-si	Gyeongsangnam-do
Mexico	Investigational Site Number : 4840007	Benito Juarez	Ciudad De Mexico
Netherlands	Investigational Site Number : 5280002	Breda
Netherlands	Investigational Site Number : 5280004	Rotterdam
Netherlands	Investigational Site Number : 5280001	Utrecht
Poland	Investigational Site Number : 6160001	Chorzow
Poland	Investigational Site Number : 6160006	Gdansk	Pomorskie
Poland	Investigational Site Number : 6160003	Katowice	Slaskie
Poland	Investigational Site Number : 6160007	Warszawa
Poland	Investigational Site Number : 6160009	Warszawa
South Africa	Investigational Site Number : 7100002	Cape Town
South Africa	Investigational Site Number : 7100010	Cape Town
South Africa	Investigational Site Number : 7100011	Cape Town
South Africa	Investigational Site Number : 7100009	Claremont
South Africa	Investigational Site Number : 7100012	Durban
South Africa	Investigational Site Number : 7100008	Johannesburg
South Africa	Investigational Site Number : 7100006	Kempton Park
South Africa	Investigational Site Number : 7100005	Middelburg
South Africa	Investigational Site Number : 7100003	Pretoria
South Africa	Investigational Site Number : 7100014	Pretoria
South Africa	Investigational Site Number : 7100004	Reiger Park
South Africa	Investigational Site Number : 7100007	Sandton
Spain	Investigational Site Number : 7242505	Alicante
Spain	Investigational Site Number : 7240002	Badalona	Catalunya [Cataluña]
Spain	Investigational Site Number : 7242501	Córdoba
Spain	Investigational Site Number : 7242503	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240006	Valencia
Taiwan	Investigational Site Number : 1583201	Kaohsiung 833
Taiwan	Investigational Site Number : 1580002	New Taipei City
Taiwan	Investigational Site Number : 1583202	Taichung
Taiwan	Investigational Site Number : 1580001	Taipei
Taiwan	Investigational Site Number : 1583203	Taoyuan County
United Kingdom	Investigational Site Number : 8260002	Edinburgh
United Kingdom	Investigational Site Number : 8260001	London	London, City Of
United Kingdom	Investigational Site Number : 8262601	London	London, City Of

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Argentina,  Brazil,  Canada,  Chile,  China,  Czechia,  Denmark,  France,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)	Percentage of participants who experienced TEAEs from baseline during the study	Baseline up to end of study (EOS) (Week 176)
Primary	Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)	Percentage of participants who experienced TESAEs from baseline during the study	Baseline up to EOS (Week 176)
Secondary	Percentage of participants who experienced Treatment-Emergent Adverse Events of Special Interest (AESI)	Percentage of participants who experienced AESI from baseline during the study	Baseline up to EOS (Week 176)
Secondary	Percentage of participants with Potentially Clinically Significant Abnormalities (PCSA) for vital signs and clinical laboratory assessments, and electrocardiogram (ECG)		Baseline up to EOS (Week 176)
Secondary	Percentage of participants discontinued from study treatment due to Adverse Events (AEs)		Baseline up to EOS (Week 176)
Secondary	Percent change from baseline in Eczema Area and Severity Index (EASI) score	The EASI is an Investigator-assessed tool used to measure the extent (area) and severity of AD. The severity is assessed based on 4 disease characteristics (erythema, induration/papulation, excoriation and lichenification). The extent of involvement of AD is assessed in 4 body regions (head/neck, trunk, upper extremities and lower extremities). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with at least a =75% reduction in EASI score (EASI-75) from baseline	EASI75: = 75% reduction in EASI score from baseline	Baseline to EOS (Week 176)
Secondary	Proportion of participants with EASI-50 /EASI-90 /EASI-100	EASI-50: =50% reduction in EASI score from baseline; EASI-90: =90% reduction in EASI score from baseline; EASI-100: =100% reduction in EASI score from baseline.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction of =2 points from baseline	The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).	Baseline to EOS (Week 176)
Secondary	Proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) from baseline	The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).	Baseline to EOS (Week 176)
Secondary	Change in percent Body Surface Area (BSA) affected by AD from baseline	BSA affected by AD will measure the extent (area) of the disease.	Baseline to EOS (Week 176)
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline	The SCORAD Index is a clinical tool used to standardise the evaluation of the extent and severity of AD. To determine the extent of AD, the affected area (A) as a percentage of the whole body is determined, with a maximum score of 100%. The severity (B) of 6 specific symptoms of AD (redness, swelling, oozing/crusting, scratch marks, skin thickening [lichenification], dryness [area where there is no inflammation]) is assessed on a 4-point scale, with a maximum score of 18: none (0), mild (1), moderate (2) or severe (3). Subjective symptoms (C): itch and sleeplessness are recorded as scored by the participants or relative on a visual analogue scale (VAS), where 0 = no itch (or sleeplessness) and 10 = worst imaginable itch (or sleeplessness), with a maximum possible score of 20.	Baseline to EOS (Week 176)
Secondary	Proportion of participants requiring rescue treatment at each visit		Baseline to EOS (Week 176)
Secondary	Proportion of participants with =4-point reduction in weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) from baseline in participants with baseline weekly average of daily PP-NRS =4	The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.	Baseline to EOS (Week 176)
Secondary	Percent change in weekly average of daily PP-NRS from baseline	The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.	Baseline to EOS (Week 176)
Secondary	Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline	The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD during the past 24 hours, with 0 = no pain and 10 = worst possible pain imaginable.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with a reduction in weekly average of daily SP-NRS =4 from baseline in participants with baseline weekly average of daily SP-NRS =4	The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD during the past 24 hours, with 0 = no pain and 10 = worst possible pain imaginable.	Baseline to EOS (Week 176)
Secondary	Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline	The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD, with 0 being 'no sleep loss related to the symptoms of atopic dermatitis' and 10 being 'I did not sleep at all' due to the symptoms of atopic dermatitis".	Baseline to EOS (Week 176)
Secondary	Proportion of participants with a reduction in weekly average of daily SD-NRS =2 from baseline in participants with Baseline weekly average of daily SDNRS =2	The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD, with 0 being 'no sleep loss related to the symptoms of atopic dermatitis' and 10 being 'I did not sleep at all' due to the symptoms of atopic dermatitis".	Baseline to EOS (Week 176)
Secondary	Change in Patient Oriented Eczema Measure (POEM) from baseline	The POEM is a 7-item self-assessment questionnaire used for monitoring atopic eczema severity, focusing on the signs and symptoms as experienced by the patient during the past 7 days. Total score ranges from 0 to 28.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with a reduction in POEM =4 from Baseline in participants with POEM baseline =4	The POEM is a 7-item self-assessment questionnaire used for monitoring atopic eczema severity, focusing on the signs and symptoms as experienced by the patient during the past 7 days. Total score ranges from 0 to 28.	Baseline to EOS (Week 176)
Secondary	Proportion of adolescent participants with a reduction in POEM =6 from Baseline in adolescents participants with POEM baseline =6	The POEM is a 7-item self-assessment questionnaire used for monitoring atopic eczema severity, focusing on the signs and symptoms as experienced by the patient during the past 7 days. Total score ranges from 0 to 28.	Baseline to EOS (Week 176)
Secondary	Change in Atopic Dermatitis Control Test (ADCT) from baseline	The ADCT is a 6-item patient-reported outcomes instrument with a 7-day recall period to measure AD disease control. Total score ranges from 0 to 24.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with a reduction in ADCT =5 from baseline in participants with baseline ADCT=5	The ADCT is a 6-item patient-reported outcomes instrument with a 7-day recall period to measure AD disease control. Total score ranges from 0 to 24.	Baseline to EOS (Week 176)
Secondary	Change in Dermatology Quality of Life Index (DLQI) from baseline in participants with age =16 years old	The DLQI is a 10-item questionnaire to measure dermatology specific quality of life (QoL), covering the participant's previous week (i.e. past 7 days). Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.	Baseline to EOS (Week 176)
Secondary	Change in Children's Dermatology Life Quality Index (CDLQI) from baseline in participants with age =12 to <16 years old	The CDLQI is a 10-item questionnaire to assess the impact of skin disease on a child's health related quality of life (HRQoL) over a recall period of 1 week. It is validated in children aged 4 to <16 years. Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with age =12 to <16 with a reduction in CDLQI =4 from Baseline in participants with age =12 to <16 with CDLQI at baseline =4	The CDLQI is a 10-item questionnaire to assess the impact of skin disease on a child's health related quality of life (HRQoL) over a recall period of 1 week. It is validated in children aged 4 to <16 years. Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with a reduction in DLQI =4 from Baseline in participants with age =16 years old and with DLQI at baseline =4	The DLQI is a 10-item questionnaire to measure dermatology specific quality of life (QoL), covering the participant's previous week (i.e. past 7 days). Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.	Baseline to EOS (Week 176)
Secondary	Change in Patient Global Impression of Severity (PGIS) from baseline	The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.	Baseline to EOS (Week 176)
Secondary	Proportions of participants who report symptoms to be "No" on the PGIS score	The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.	Baseline to EOS (Week 176)
Secondary	Proportions of participants who report symptoms to be "No" or "Mild" on the PGIS score	The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.	Baseline to EOS (Week 176)
Secondary	Proportion of participants who respond "Much better" on the Patient Global Impression of (PGIC) scale	The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.	Week 16 to EOS (Week 176)
Secondary	Proportion of participants who respond "Much better" or "A little better" on the PGIC scale	The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.	Week 16 to EOS (Week 176)
Secondary	Proportion of participants by PGIC responses	The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.	Week 16 to EOS (Week 176)
Secondary	Change in Hospital Anxiety Depression Scale (HADS) from baseline	The HADS is a 14-item patient-reported outcomes measure used to assess states of anxiety and depression over the past week. It is comprised of 7 items assessing anxiety and depression respectively. A Total score is out of 42 (21 per subscale). Higher scores indicate greater levels of anxiety and/or depression.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A =8	The HADS is a 14-item patient-reported outcomes measure used to assess states of anxiety and depression over the past week. It is comprised of 7 items assessing anxiety and depression respectively. A Total score is out of 42 (21 per subscale). Higher scores indicate greater levels of anxiety and/or depression.; HADS-A is the anxiety HADS subscale.	Baseline to EOS (Week 176)
Secondary	Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D Baseline =8	The HADS is a 14-item patient-reported outcomes measure used to assess states of anxiety and depression over the past week. It is comprised of 7 items assessing anxiety and depression respectively. A Total score is out of 42 (21 per subscale). Higher scores indicate greater levels of anxiety and/or depression.; HADS-D is the depression HADS subscale.	Baseline to EOS (Week 176)