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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05162586




Registration number
NCT05162586
Ethics application status
Date submitted
8/12/2021
Date registered
17/12/2021

Titles & IDs
Public title
The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
Scientific title
A Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging, Parallel and Adaptive Study to Evaluate the Efficacy and Safety of Enpatoran in SLE and in CLE (SCLE and/or DLE) Participants Receiving Standard of Care (WILLOW)
Secondary ID [1] 0 0
2021-004648-27
Secondary ID [2] 0 0
MS200569_0003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enpatoran low dose
Treatment: Drugs - Enpatoran medium dose
Treatment: Drugs - Enpatoran high dose
Treatment: Drugs - Placebo

Placebo comparator: Cohort A: Placebo - Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (Cutaneous Lupus Erythematosus Disease Area and Severity Index \[CLASI-A\] greater than or equal to \[\>=\] 8) will be enrolled in Cohort A to receive placebo matched to Enpatoran.

Experimental: Cohort A: Enpatoran low dose - Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive low dose of Enpatoran.

Experimental: Cohort A: Enpatoran medium dose - Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive medium dose of Enpatoran.

Experimental: Cohort A: Enpatoran high dose - Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive high dose of Enpatoran.

Placebo comparator: Cohort B (Part 1 + Part 2): Placebo - Participants with active SLE who have moderate to high systemic disease activity (British Isles Lupus Assessment Group \[BILAG A/2B\]) with 1 or 2 of the following: CLASI-A \>= 8 and/or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \>= 6 will be enrolled in Cohort B to receive placebo matched to Enpatoran .

Experimental: Cohort B (Part 1 + Part 2): Enpatoran high dose - Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive high dose of Enpatoran.

Experimental: Cohort B (Part 2): Enpatoran low dose - Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive low dose of M5049.

Experimental: Cohort B (Part 2): Enpatoran medium dose - Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive medium dose of Enpatoran.


Treatment: Drugs: Enpatoran low dose
Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.

Treatment: Drugs: Enpatoran medium dose
Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.

Treatment: Drugs: Enpatoran high dose
Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.

Treatment: Drugs: Placebo
Participants will receive placebo matched to Enpatoran up to 24 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16
Timepoint [1] 0 0
Baseline, Week 16
Primary outcome [2] 0 0
Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24
Timepoint [2] 0 0
At Week 24
Secondary outcome [1] 0 0
Cohort A and Cohort B: Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs of Special Interest, Clinically Significant Abnormalities in Laboratory Parameters and QT Interval Corrected
Timepoint [1] 0 0
Baseline (Day 1) up to End of Safety Follow-up Period (Week 33)
Secondary outcome [2] 0 0
Cohort A and Cohort B: Change from Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) at Week 16 and Week 24
Timepoint [2] 0 0
Baseline, Week 16 and 24
Secondary outcome [3] 0 0
Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24
Timepoint [3] 0 0
Baseline, Week 16 and 24
Secondary outcome [4] 0 0
Cohort B: Participants with British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response and with Clinically Meaningful Corticosteroids (CS) Reduction
Timepoint [4] 0 0
Day 1 up to Week 24
Secondary outcome [5] 0 0
Cohort A: Clinically Meaningful Corticosteroids (CS) Reduction
Timepoint [5] 0 0
Day 1 up to Week 24
Secondary outcome [6] 0 0
Cohort A: Ocurrence of Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Score 0 or 1 at Week 16 and Week 24
Timepoint [6] 0 0
At Week 16 and 24
Secondary outcome [7] 0 0
Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24
Timepoint [7] 0 0
At Week 24
Secondary outcome [8] 0 0
Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24
Timepoint [8] 0 0
At Week 24
Secondary outcome [9] 0 0
Cohort B: Remission Attainment at Week 24
Timepoint [9] 0 0
At Week 24
Secondary outcome [10] 0 0
Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Cohort B: Change from Baseline in Physician's Global Assessment at Week 24
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare
Timepoint [12] 0 0
Day 1 through Week 24
Secondary outcome [13] 0 0
Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare
Timepoint [13] 0 0
Day 1 through Week 24
Secondary outcome [14] 0 0
Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24
Timepoint [14] 0 0
Baseline, Week 24
Secondary outcome [15] 0 0
Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24
Timepoint [17] 0 0
Baseline, Week 24

Eligibility
Key inclusion criteria
* Active CLE (SCLE and/or DLE) with a CLE disease area and activity index (CLASI-A) >= 8
* Active SLE with presence of: CLASI-A >= 8 and BILAG 2004 1B, C, D (that is [i.e.], No BILAG 2004 A and No BILAG 2004 >= 2B) or BILAG 2004 >= 1A or 2B and 1 or 2 of the following: Hybrid Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI >= 6 at Screening Visit and confirmed clinical hybrid SELENA-SLEDAI >= 4 (excluding laboratory parameters) at Day 1 Visit and/or CLASI-A >= 8
* Receiving a stable dose of at least one of the following standards of care therapies for lupus: Immunomodulator/immunosuppressant, oral corticosteroids, and/or topical corticosteroids
* Other protocol defined inclusion criteria could apply
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Autoimmune or rheumatic disease other than SLE or CLE
* Dermatological diseases other than cutaneous manifestations of SLE or CLE
* Uncontrolled medical conditions including significant cardiovascular events, active lupus nephritis, and active neurological disorder
* Ongoing or active clinically significant viral, bacterial, or fungal infection
* History of uncontrolled seizures or other neurological disorder
* History of or positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
* History of malignancy
* Other protocol defined exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/12/2024
Actual
Sample size
Target
532
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Box Hill Hospital - PARENT - Caulfield
Recruitment hospital [2] 0 0
Monash Medical Centre Clayton - Clayton
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Haematology - Murdoch
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - PARENT - Parkville
Recruitment hospital [5] 0 0
Westmead Hospital - SUPERSEDED - Westmead
Recruitment hospital [6] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Caulfield
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Murdoch
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment postcode(s) [5] 0 0
- Westmead
Recruitment postcode(s) [6] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
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North Carolina
Country [8] 0 0
United States of America
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Ohio
Country [9] 0 0
United States of America
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Oklahoma
Country [10] 0 0
United States of America
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Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
Argentina
State/province [13] 0 0
Ciudad Autonoma Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Ciudad Autonoma de Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Mar del Plata
Country [16] 0 0
Argentina
State/province [16] 0 0
Mendoza
Country [17] 0 0
Argentina
State/province [17] 0 0
Rosario
Country [18] 0 0
Argentina
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Salta
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Argentina
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San Fernando
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Argentina
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San Juan
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Argentina
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San Miguel de Tucuman
Country [22] 0 0
Argentina
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San Miguel
Country [23] 0 0
Argentina
State/province [23] 0 0
Tucuman
Country [24] 0 0
Brazil
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Belo Horizonte
Country [25] 0 0
Brazil
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Cuiabá
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Brazil
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Curitiba
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Brazil
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Fortaleza
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Brazil
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Juiz de Fora
Country [29] 0 0
Brazil
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Lajeado
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Brazil
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Porto Alegre
Country [31] 0 0
Brazil
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Salvador
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Brazil
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Sao Jose do Rio Preto
Country [33] 0 0
Brazil
State/province [33] 0 0
Sao Paulo
Country [34] 0 0
Brazil
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São Paulo
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Haskovo
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Plovdiv
Country [37] 0 0
Bulgaria
State/province [37] 0 0
Ruse
Country [38] 0 0
Bulgaria
State/province [38] 0 0
Sevlievo
Country [39] 0 0
Bulgaria
State/province [39] 0 0
Sofia
Country [40] 0 0
Bulgaria
State/province [40] 0 0
Stara Zagora
Country [41] 0 0
Chile
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Osorno
Country [42] 0 0
Chile
State/province [42] 0 0
Santiago
Country [43] 0 0
China
State/province [43] 0 0
Baotou
Country [44] 0 0
China
State/province [44] 0 0
Beijing
Country [45] 0 0
China
State/province [45] 0 0
Changchun
Country [46] 0 0
China
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Changsha
Country [47] 0 0
China
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Chengdu
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China
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Guangzhou
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China
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Haikou
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China
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Hohhot
Country [51] 0 0
China
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Luoyang
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China
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Nanchang
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China
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Nanjing
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China
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Shanghai
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China
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SuZhou
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China
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Tianjin
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China
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Xi'an
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Colombia
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Barranquilla
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Colombia
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Bogotá
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Colombia
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Bucaramanga
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Colombia
State/province [61] 0 0
Medellin
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Colombia
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Zipaquirá
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Greece
State/province [63] 0 0
Athens
Country [64] 0 0
Greece
State/province [64] 0 0
Patra
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Greece
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Thessaloniki
Country [66] 0 0
Israel
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Ramat Gan
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Japan
State/province [67] 0 0
Asahikawa-shi
Country [68] 0 0
Japan
State/province [68] 0 0
Chiba-shi
Country [69] 0 0
Japan
State/province [69] 0 0
Chuo-ku
Country [70] 0 0
Japan
State/province [70] 0 0
Hiroshima-shi
Country [71] 0 0
Japan
State/province [71] 0 0
Kagoshima-shi
Country [72] 0 0
Japan
State/province [72] 0 0
Kanazawa-shi
Country [73] 0 0
Japan
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Kawagoe-shi
Country [74] 0 0
Japan
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Kita-gun
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Japan
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Meguro-ku
Country [76] 0 0
Japan
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Sapporo-shi
Country [77] 0 0
Japan
State/province [77] 0 0
Sendai-shi
Country [78] 0 0
Japan
State/province [78] 0 0
Toon-shi
Country [79] 0 0
Korea, Republic of
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Busan
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Korea, Republic of
State/province [80] 0 0
Incheon
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Seoul
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Korea, Republic of
State/province [82] 0 0
Suwon
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Mauritius
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Quatre Bornes
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Mexico
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Ciudad de México
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Mexico
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Cuernavaca
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Mexico
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Guadalajara
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Mexico
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Mexicali
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Mexico
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Mexico
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Mexico
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Monterrey
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Mexico
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Torreon
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Mexico
State/province [91] 0 0
Yucatan
Country [92] 0 0
Moldova, Republic of
State/province [92] 0 0
Chisinau
Country [93] 0 0
Philippines
State/province [93] 0 0
Cebu City
Country [94] 0 0
Philippines
State/province [94] 0 0
Davao City
Country [95] 0 0
Philippines
State/province [95] 0 0
Iloilo City
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Philippines
State/province [96] 0 0
Lipa City
Country [97] 0 0
Philippines
State/province [97] 0 0
Manila
Country [98] 0 0
Philippines
State/province [98] 0 0
Quezon City
Country [99] 0 0
Poland
State/province [99] 0 0
Bialystok
Country [100] 0 0
Poland
State/province [100] 0 0
Koscian
Country [101] 0 0
Poland
State/province [101] 0 0
Krakow
Country [102] 0 0
Poland
State/province [102] 0 0
Opole
Country [103] 0 0
Poland
State/province [103] 0 0
Poznan
Country [104] 0 0
Poland
State/province [104] 0 0
Szczecin
Country [105] 0 0
Poland
State/province [105] 0 0
Warszawa
Country [106] 0 0
Romania
State/province [106] 0 0
Bucharest
Country [107] 0 0
Romania
State/province [107] 0 0
Bucuresti
Country [108] 0 0
Romania
State/province [108] 0 0
Ramnicu Valcea
Country [109] 0 0
Serbia
State/province [109] 0 0
Belgrade
Country [110] 0 0
Serbia
State/province [110] 0 0
Kragujevac
Country [111] 0 0
South Africa
State/province [111] 0 0
Cape Town
Country [112] 0 0
South Africa
State/province [112] 0 0
Pretoria
Country [113] 0 0
South Africa
State/province [113] 0 0
Umhlanga
Country [114] 0 0
Spain
State/province [114] 0 0
Castelló
Country [115] 0 0
Spain
State/province [115] 0 0
La Coruña
Country [116] 0 0
Spain
State/province [116] 0 0
Madrid
Country [117] 0 0
Spain
State/province [117] 0 0
Málaga
Country [118] 0 0
Spain
State/province [118] 0 0
Santander
Country [119] 0 0
Spain
State/province [119] 0 0
Sevilla
Country [120] 0 0
Spain
State/province [120] 0 0
Valencia
Country [121] 0 0
Spain
State/province [121] 0 0
Valladolid
Country [122] 0 0
Taiwan
State/province [122] 0 0
Kaohsiung
Country [123] 0 0
Taiwan
State/province [123] 0 0
Taipei City
Country [124] 0 0
Taiwan
State/province [124] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
EMD Serono Research & Development Institute, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Available to whom?
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://bit.ly/IPD21


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05162586