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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04895241




Registration number
NCT04895241
Ethics application status
Date submitted
17/05/2021
Date registered
20/05/2021
Date last updated
19/09/2024

Titles & IDs
Public title
A Study to Learn About the Safety of Litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus
Scientific title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Litifilimab (BIIB059) in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Nonbiologic Lupus Standard of Care
Secondary ID [1] 0 0
2023-505695-30
Secondary ID [2] 0 0
230LE303
Universal Trial Number (UTN)
Trial acronym
TOPAZ-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Erythematosus, Systemic 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 - Litifilimab
Treatment: Drugs - Placebo

Experimental: Litifilimab High Dose - Participants who are receiving background nonbiologic lupus SOC therapy will receive high dose of litifilimab, subcutaneously (SC) every 4 weeks (Q4W), up to Week 48 with an additional dose at Week 2.

Experimental: Litifilimab Low Dose - Participants who are receiving background nonbiologic lupus SOC therapy will receive low dose of litifilimab, SC Q4W, up to Week 48 with an additional dose at Week 2.

Placebo comparator: Placebo - Participants who are receiving background nonbiologic lupus SOC therapy will receive litifilimab-matching placebo, SC Q4W, up to Week 48 with an additional dose at Week 2.


Treatment: Drugs: Litifilimab
Administered as specified in the treatment arm.

Treatment: Drugs: Placebo
Administered as specified in the treatment arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index of 4 (SRI-4) Response at Week 52
Timepoint [1] 0 0
Week 52
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved an SRI-4 Response at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Percentage of Participants With at Least 4 Joints (Both Swollen and Tender) at Baseline Who Achieved a Joint-50 Response at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Percentage of Participants with OCS =10 milligrams per day (mg/day) at Baseline Who Have OCS Reduction to =7.5 mg/day at Week 40, Which Is Sustained Through Week 52 with No Disease Worsening from Week 40 to Week 52
Timepoint [3] 0 0
Week 40 to Week 52
Secondary outcome [4] 0 0
Percentage of Participants with a CLASI-A score =10 at Baseline Who Achieved a 50% Improvement From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI-50) Response at Week 16
Timepoint [4] 0 0
Week 16
Secondary outcome [5] 0 0
Annualized Flare Rate Through Week 52
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
Change from Baseline in Physician's Global Assessment (PGA) Visual Analog Scale (VAS) Score by Visit
Timepoint [6] 0 0
Up to Week 52
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved a British Isles Lupus Activity Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response by Visit
Timepoint [7] 0 0
Up to Week 52
Secondary outcome [8] 0 0
Time to Onset of SRI-4 Response Sustained Through Week 52
Timepoint [8] 0 0
Up to Week 52
Secondary outcome [9] 0 0
Percentage of Participants Who Achieved SRI-4, -5, or -6 Response by Visit
Timepoint [9] 0 0
Up to Week 52
Secondary outcome [10] 0 0
Percentage of Participants with Joint-50 Response by Visit
Timepoint [10] 0 0
Up to Week 52
Secondary outcome [11] 0 0
Percentage of Participants with Baseline CLASI-A Score =10 Who Achieved a CLASI-20, -50, -70, or -90 Response by Visit
Timepoint [11] 0 0
Up to Week 52
Secondary outcome [12] 0 0
Percentage of Participants with Baseline CLASI-A Score =10 Who Achieved a CLASI-A Score of = 1 by Visit
Timepoint [12] 0 0
Up to Week 52
Secondary outcome [13] 0 0
Time to First British Isles Lupus Activity Group-2004 (BILAG-2004) Severe Flare by Visit
Timepoint [13] 0 0
Up to Week 52
Secondary outcome [14] 0 0
Time to First Severe Flare as defined by the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI)
Timepoint [14] 0 0
Up to Week 52
Secondary outcome [15] 0 0
Percentage of Time Spent in Lupus Low Disease Activity State (LLDAS)
Timepoint [15] 0 0
Up to Week 52
Secondary outcome [16] 0 0
Percentage of Participants With Sustained LLDAS as Defined by the Number of Participants With = 3, = 5, and = 7 Consecutive Visits in LLDAS up to and Including Week 52
Timepoint [16] 0 0
Up to Week 52
Secondary outcome [17] 0 0
Percentage of Participants who Achieved LLDAS at Week 52
Timepoint [17] 0 0
Week 52
Secondary outcome [18] 0 0
Percentage of Participants With Baseline OCS =10 mg/day Who Achieved =7.5 mg/day at Week 52
Timepoint [18] 0 0
Week 52
Secondary outcome [19] 0 0
Change from Baseline in Lupus-Specific Health-Related Quality-of-Life Questionnaire (LupusQoL) Score
Timepoint [19] 0 0
Up to Week 52
Secondary outcome [20] 0 0
Change From Baseline in Short Form Health Survey-36 (SF-36) Score
Timepoint [20] 0 0
Up to Week 52
Secondary outcome [21] 0 0
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score
Timepoint [21] 0 0
Up to Week 52
Secondary outcome [22] 0 0
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score
Timepoint [22] 0 0
Up to Week 52
Secondary outcome [23] 0 0
Change From Baseline in Work Productivity and Activity Impairment (WPAI): Lupus Score
Timepoint [23] 0 0
Up to Week 52
Secondary outcome [24] 0 0
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [24] 0 0
Up to Week 52
Secondary outcome [25] 0 0
Number of Participants with Antibodies to Litifilimab
Timepoint [25] 0 0
Up to Week 52

Eligibility
Key inclusion criteria
Key

* Participant must be diagnosed with systemic lupus erythematosus (SLE) at least 24 weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria for SLE at screening by a qualified physician.
* Participant has a modified Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score = 6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated).
* Participant has a modified clinical SLEDAI-2K score = 4 (excluding anti-dsDNA, low complement component 3 (C3) and/or complement component 4 (C4), alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization.
* Participant has BILAG-2004 grade A in = 1 organ system or BILAG-2004 grade B in = 2 organ systems at Screening (adjudicated) and randomization.
* Participant must be treated with one of the following background nonbiologic lupus SOC therapies, initiated = 12 weeks prior to Screening and at stable dose = 4 weeks prior to randomization:

1. Antimalarials as stand-alone treatment
2. Antimalarial treatment in combination with OCS and/or a single immunosuppressant
3. Treatment with OCS and/or a single immunosuppressant

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of or positive test result for human immunodeficiency virus (HIV).
* Current hepatitis C infection (defined as positive hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid [RNA]).
* Current hepatitis B infection (defined as positive for antibody to hepatitis B surface antigen (HBsAg) and/or positive for total hepatitis antibody to B core antigen [anti-HBc] with positive reflex HBV DNA).
* History of severe herpes infection.
* Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure.
* Active severe lupus nephritis where, in the opinion of the Investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach is indicated, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol is indicated; or urine protein-creatinine ratio > 2.0 or severe chronic kidney disease (estimated glomerular filtration rate < 30 milliliters per minute per 1.73 meter square [mL/min/1.73 m^2]) calculated using the abbreviated modification of diet in renal disease equation.
* Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-induced lupus.
* History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome.
* Active neuropsychiatric SLE.
* Use of oral prednisone (or equivalent) above 20 mg/day.

Note: Other protocol defined Inclusion/Exclusion criteria may 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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/09/2025
Actual
Sample size
Target
540
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Footscray Hospital - Footscray
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Brazil
State/province [14] 0 0
Bahia
Country [15] 0 0
Brazil
State/province [15] 0 0
Ceará
Country [16] 0 0
Brazil
State/province [16] 0 0
Distrito Federal
Country [17] 0 0
Brazil
State/province [17] 0 0
Espírito Santo
Country [18] 0 0
Brazil
State/province [18] 0 0
Mato Grosso
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Brazil
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Minas Gerais
Country [20] 0 0
Brazil
State/province [20] 0 0
Paraná
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Brazil
State/province [21] 0 0
Rio Grande Do Sul
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Brazil
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Sao Paulo
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Bulgaria
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Plovdiv
Country [24] 0 0
Bulgaria
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Ruse
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Bulgaria
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Sofia
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Chile
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Osorno
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Chile
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Santiago
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Chile
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Valdivia
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France
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Gironde
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France
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Herault
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France
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Puy De Dome
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Greece
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Athens
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Busan
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Korea, Republic of
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Incheon
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Seoul
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Mexico
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Jalisco
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Mexico
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Morelos
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Mexico
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Nuevo León
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Yucatán
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Chihuahua
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Mexico
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Durango
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Arequipa
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Lima
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Philippines
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Davao City
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Philippines
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Iloilo
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Philippines
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Lipa City
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Philippines
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Mabalacat, Pampanga
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Philippines
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Manila
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Philippines
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Quenzon City
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Philippines
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Quezon City, Metro Manila
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Poland
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Bialystok
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Bydgoszcz
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Poland
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Bytom
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Poland
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Krakow
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Lublin
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Poland
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Malbork
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Warszawa
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Poland
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Wroclaw
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Russian Federation
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Kemerovo
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Russian Federation
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Moscow
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Russian Federation
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Orenburg
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Spain
State/province [64] 0 0
Cantabria
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Spain
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Barcelona
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Spain
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Granada
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Spain
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Sevilla
Country [68] 0 0
Spain
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Valencia
Country [69] 0 0
Sweden
State/province [69] 0 0
Stockholm
Country [70] 0 0
Sweden
State/province [70] 0 0
Uppasala
Country [71] 0 0
Sweden
State/province [71] 0 0
Örebro
Country [72] 0 0
Taiwan
State/province [72] 0 0
Kaohsiung
Country [73] 0 0
Taiwan
State/province [73] 0 0
Taoyuan County

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with systemic lupus erythematosus (SLE). The study will focus on participants who have active disease and are already taking standard of care medications. These may include antimalarials, steroids, and immunosuppressants.

The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the disease. The main question researchers want to answer is:

- How many participants have an improvement in their symptoms after 52 weeks of treatment? Researchers will answer this and other questions by measuring the symptoms of SLE over time using a variety of scoring tools. These include the SLE Responder Index (SRI), the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), and the Patient Global Assessment - Visual Analog Scale (PGA-VAS).

Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and SLE have on the quality of life of participants using a group of questionnaires.

The study will be done as follows:

* After screening, participants will be randomized to receive either a high or low dose of litifilimab, or placebo. A placebo looks like the study drug but contains no real medicine.
* All participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks. The treatment period will last 52 weeks. Participants will continue to take their standard of care medications.
* Neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo.
* There will be a follow-up safety period that lasts up to 24 weeks.
* In total, participants will have up to 22 study visits. The total study duration for participants will be up to 80 weeks.
Trial website
https://clinicaltrials.gov/study/NCT04895241
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Biogen Clinical Trial Center
Address 0 0
Country 0 0
Phone 0 0
866-633-4636
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04895241