Clinical trial NCT06044337: A Long-Term Extension Study to Learn More About the Safety of Litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Active Cutaneous Lupus Erythematosus (LTE AMETHYST)
Official title: A Multicenter, Open-Label, Single-Arm, Phase 3, Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of BIIB059 (Litifilimab) in Adult Participants With Active Subacute Cutaneous Lupus Erythematosus and/or Chronic Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Subacute Cutaneous Lupus Erythematosus
Chronic Cutaneous Lupus Erythematosus
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue.

The study will enroll only those participants who have completed treatment with litifilimab in the parent study, 230LE301.

The main objective of the study is learning more about the long-term safety of litifilimab.

The main question researchers want to answer is:

- How many participants have adverse events and serious adverse events after taking litifilimab? Adverse events are unwanted medical problems that may or may not be caused by the study drug.

Researchers will also learn more about the effect of litifilimab on CLE. They will do this by measuring the symptoms of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI).

Researchers will assess the effect litifilimab and CLE has on the quality of life of participants using a group of questionnaires. They will also study how litifilimab affects laboratory tests and how participants' immune systems respond to litifilimab.

The study will be done as follows:

* The last visit of parent study 230LE301 will be the first visit of study 230LE305.
* All participants will receive litifilimab as an injection under the skin once every 4 weeks. Both researchers and participants will know the dose and identity of the study drug.
* The treatment period will last up to 104 weeks, or 2 years.
* There will be a follow-up safety period that lasts up to 24 weeks.
* In total, participants will have up to 33 study visits.
* The total study duration for participants will be up to 128 weeks.

Detailed description: The primary objective of the study is to evaluate the long-term safety and tolerability BIIB059 (litifilimab) in participants who completed the parent study 230LE301 (NCT05531565) with active subacute CLE and/or chronic CLE with or without systemic manifestations and refractory and/or intolerant to antimalarial therapy.

The secondary objectives of the study are to evaluate the long-term effect of litifilimab on disease activity and the effect of litifilimab in preventing disease damage in participants with active subacute CLE and/or chronic CLE with or without systemic manifestations and refractory and/or intolerant to antimalarials; to evaluate the long-term effect of litifilimab on preventing lupus flare in participants with CLE with SLE; to assess long-term use of oral corticosteroid (OCS) in participants receiving litifilimab treatment; to assess the impact of litifilimab on participant-reported health-related quality of life (HRQoL); to evaluate long-term effect of litifilimab on laboratory parameters; to evaluate the immunogenicity and pharmacokinetics (PK) of litifilimab.

Eligibility criteria: Key Inclusion Criteria:

* Participants who completed the parent study (230LE301 \[NCT05531565\], Part A or Part B) on study treatment (received treatment through Week 48 and attended the last study assessment visit at Week 52).
* Ability of the participant to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential health information in accordance with national and local privacy regulations.

Key Exclusion Criteria:

* Early Part A or Part B parent study (230LE301 \[NCT05531565\]) treatment terminators (participants who discontinued study treatment before Week 48).
* Early Part A or Part B parent study terminators \[participants who withdrew from parent study participation before Week 52 and did not complete the parent study extended treatment period (ETP)\].
* Participants who have developed any other medical diseases, conditions, or abnormalities, rendering their participation in the long-term extension (LTE) study unsuitable in the opinion of the Investigator.

NOTE: Other protocol- defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 128 weeks
Secondary outcomes:
measure: Percentage of Participants who Achieve a Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI)-70 Response, Defined as a 70% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Percentage of Participants who Achieve a CLASI-50 Response, Defined as a 50% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Percentage of Participants who Achieve a CLASI-90 Response, Defined as a 90% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Percentage of Participants who Achieve a Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) Erythema Score of 0 or 1
timeFrame: Up to 128 weeks
measure: Percentage of Participants who Achieve a CLA-IGA-R Other Morphologic Characteristics (OMC) Score of 0 or 1
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained CLASI-70 Response, Defined as the Number of Weeks With 70% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained CLASI-50 Response, Defined as the Number of Weeks With 50% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained CLASI-90 Response, Defined as the Number of Weeks With 90% Improvement in CLASI-A Score From the Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained Efficacy, Defined as the Number of Weeks With CLA-IGA-R Erythema Score of 0 or 1
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained Efficacy, Defined as the Number of Weeks With CLA-IGA-R OMC Score of 0 or 1 and Improvement of at Least 1 Point From Baseline Value (Parent Study [NCT05531565])
timeFrame: Up to 128 weeks
measure: Cumulative Duration of Sustained Efficacy, Defined as the Number of Weeks With CLA-IGA-R Follicular Activity Score of 0
timeFrame: Up to 128 weeks
measure: Percentage of Participants With a CLASI-70 Response Among CLASI-70 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLASI-50 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLASI-90 Response Among CLASI-90 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLA-IGA-R Erythema Score of 0 or 1 Among Participants With a CLA-IGA-R Erythema Score of 0 or 1 at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With CLA-IGA-R OMC Score of 0 or 1 and at Least 1 Level of Improvement From Baseline Value(Parent Study) Among Participants With CLA IGA R OMC Score of 0 or 1 and at Least 1 Level Improvement From Baseline Value(Parent Study)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLASI-70 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLASI-90 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With a CLASI-90 Response Among CLASI-70 Responders at Week 52 of the Parent Study (NCT05531565)
timeFrame: Day 0 (Week 52 of parent study) up to 128 weeks
measure: Percentage of Participants With Loss of Response, Defined as an Increase of ≥ 7 Points in CLASI-A Total Score From Baseline
timeFrame: Baseline (Day 0) up to 128 weeks
measure: Percentage of Participants With Loss of Response, Defined as Achieving 2 Points Improvement From Baseline Value(Parent Study) CLA-IGA-R Erythema Score at Beginning of/During LTE Study and Then Relapsing to CLA-IGA-R Erythema Baseline Value(Parent Study)
timeFrame: Up to 128 weeks
measure: Percentage of Participants With Loss of Response, Defined as Having at Least 2, 3, and 4 Points Worsening in CLA-IGA-R Erythema Score From Their Minimum Score in the Parent Study (NCT05531565)
timeFrame: Up to 128 weeks
measure: Absolute Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index Damage (CLASI-D) Score From Baseline Value (Parent Study [NCT05531565]) to Week 104
timeFrame: Up to 104 weeks
measure: Percent Change in CLASI-D Score From Baseline Value (Parent Study [NCT05531565]) to Week 104
timeFrame: Up to 104 weeks
measure: Annualized Mild/Moderate and Severe Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index Flare Index (SFI) Rates Through Week 52
timeFrame: Up to 52 weeks
measure: Annualized Mild/Moderate and Severe SFI Rates Through Week 104
timeFrame: Up to 104 weeks
measure: Percentage of Participants With Oral Corticosteroid (OCS) Dose
timeFrame: Up to 104 weeks
measure: Percentage of Participants With OCS ≤ 7.5 Milligrams per day (mg/day)
timeFrame: Up to 104 weeks
measure: Percentage of Participants With OCS ≤ 5.0 mg/day
timeFrame: Up to 104 weeks
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Cutaneous Lupus Erythematosus - Quality of Life (CLE-QoL) at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in European Quality of Life - 5-Dimensions Questionnaire, 3-Level Version (EQ-5D-3L) at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in 36-Item Short Form Survey (SF-36) (acute version) at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Work Productivity and Activity Impairment (WPAI): Lupus at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Patient Health Questionnaire-9 (PHQ-9) at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Subject Global Assessment of Skin - Follow-up (SGA-Skin-FU) at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Numerical Rating Scale (NRS) for Pain in Skin Rash at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Change From Baseline Value (Parent Study [NCT05531565]) in Numerical Rating Scale (NRS) for Itch in Skin Rash at Weeks 52 and 104
timeFrame: Baseline, Weeks 52 and 104
measure: Number of Participants With Clinically Relevant Change From Baseline Value (Parent Study [NCT05531565]) in Standard Laboratory Parameters
timeFrame: Up to 128 weeks
measure: Number of Participants With Clinically Relevant Change From Baseline Value (Parent Study [NCT05531565]) in Electrocardiogram (ECG) Results
timeFrame: Up to 104 weeks
measure: Number of Participants With Anti-BIIB059 Antibodies in Serum
timeFrame: Up to 128 weeks
measure: Serum Concentration of Litifilimab
timeFrame: Pre-dose up to 128 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Ann Arbor
country: United States
facility: David Fivenson, MD, Dermatology, PLLC
state: Michigan
city: Troy
country: United States
facility: Revival Research Institute, LLC
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Chapel Hill
country: United States
facility: Thurston Arthritis Research Center
state: North Carolina
city: Durham
country: United States
facility: Duke Dermatology South Durham
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Grapevine
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman
state: Tucuman
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: APRILLUS Asistencia e Investigacion
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
state: Sao Paulo
city: Sofia
country: Bulgaria
facility: DCC 'Alexandrovska', EOOD
city: Sofia
country: Bulgaria
facility: DCC Focus 5 - MEOH OOD
city: Calgary
country: Canada
facility: Laser Rejuvenation Clinics, Inc.
state: Alberta
city: Sherbrooke
country: Canada
facility: DIEX Recherche Sherbrooke Inc.
state: Quebec
city: Las Condes
country: Chile
facility: Centro Medico SkinMed
city: Santiago
country: Chile
facility: CIEC - Centro Internacional de Estudios Clínicos
city: Valdivia
country: Chile
facility: Clinical Research Chile SpA
city: Toulouse Cedex 9
country: France
facility: Hopital Larrey
state: Haute Garonne
city: Lyon
country: France
facility: Hopital Edouard Herriot - CHU Lyon
state: Rhone
city: Paris
country: France
facility: Hopital Tenon
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
state: Bayern
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim Dermatologie
state: Niedersachsen
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg AoeR
state: Niedersachsen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
state: Nordrhein Westfalen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
state: Sachsen Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU
state: Sachsen
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Firenze
country: Italy
facility: Università degli studi di Firenze
city: Milan
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa-Ken
city: Itabashi-ku
country: Japan
facility: Teikyo University Hospital
state: Tokyo-To
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Ciudad de Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
state: Distrito Federal
city: Chihuahua
country: Mexico
facility: Investigacion y Biomedicina de Chihuahua, S.C.
city: Guadalajara
country: Mexico
facility: Centro de investigacion medica y reumatologia
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Kosice
country: Slovakia
facility: Artromac n.o.
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
state: Cantabria
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Córdoba
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset - Solna
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Lucerne (Luzern)
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
state: West Midlands
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: