A Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of BIIB059 (Litifilimab) in Adults With Active Subacute Cutaneous Lupus Erythematosus (CLE) and/or Chronic CLE With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy (AMETHYST LTE)

• ClinicalTrials.gov Identifier: NCT06044337
• Recruitment Status: Enrolling by invitation
• First Posted: September 21, 2023
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

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 systemic lupus erythematosus (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.

Condition or disease	Intervention/treatment	Phase
Subacute Cutaneous Lupus Erythematosus; Chronic Cutaneous Lupus Erythematosus	Drug: BIIB059 (litifilimab)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 322 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 3, 2023
• Estimated Primary Completion Date: June 26, 2029
• Estimated Study Completion Date: December 11, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: BIIB059; Participants will receive BIIB059 subcutaneously, once every 4 weeks up to Week 100.	Drug: BIIB059 (litifilimab); Administered as specified in the treatment arm.; Other Name: litifilimab

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 128 weeks ]

Secondary Outcome Measures :

1. 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]) [ Time Frame: Up to 128 weeks ]
2. 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]) [ Time Frame: Up to 128 weeks ]
3. 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]) [ Time Frame: Up to 128 weeks ]
4. Percentage of Participants who Achieve a Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) Erythema Score of 0 or 1 [ Time Frame: Up to 128 weeks ]
5. Percentage of Participants who Achieve a CLA-IGA-R Other Morphologic Characteristics (OMC) Score of 0 or 1 [ Time Frame: Up to 128 weeks ]
6. 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]) [ Time Frame: Up to 128 weeks ]
7. 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]) [ Time Frame: Up to 128 weeks ]
8. 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]) [ Time Frame: Up to 128 weeks ]
9. Cumulative Duration of Sustained Efficacy, Defined as the Number of Weeks With CLA-IGA-R Erythema Score of 0 or 1 [ Time Frame: Up to 128 weeks ]
10. 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]) [ Time Frame: Up to 128 weeks ]
11. Cumulative Duration of Sustained Efficacy, Defined as the Number of Weeks With CLA-IGA-R Follicular Activity Score of 0 [ Time Frame: Up to 128 weeks ]
12. Percentage of Participants With a CLASI-70 Response Among CLASI-70 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
13. Percentage of Participants With a CLASI-50 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
14. Percentage of Participants With a CLASI-90 Response Among CLASI-90 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
15. 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) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
16. 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) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
17. Percentage of Participants With a CLASI-70 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
18. Percentage of Participants With a CLASI-90 Response Among CLASI-50 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
19. Percentage of Participants With a CLASI-90 Response Among CLASI-70 Responders at Week 52 of the Parent Study (NCT05531565) [ Time Frame: Day 0 (Week 52 of parent study) up to 128 weeks ]
20. Percentage of Participants With Loss of Response, Defined as an Increase of ≥ 7 Points in CLASI-A Total Score From Baseline [ Time Frame: Baseline (Day 0) up to 128 weeks ]
21. 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) [ Time Frame: Up to 128 weeks ]
22. 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 Parent Study (NCT05531565) [ Time Frame: Up to 128 weeks ]
23. Absolute Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index Damage (CLASI-D) Score From the Baseline (Parent Study [NCT05531565]) to Week 104 [ Time Frame: Up to 104 weeks ]
24. Percent Change in CLASI-D Score From the Baseline (Parent Study [NCT05531565]) to Week 104 [ Time Frame: Up to 104 weeks ]
25. Annualized Mild/Moderate and Severe Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index Flare Index (SFI) Rates From Baseline Value (Parent Study [NCT05531565]) Through Week 52 [ Time Frame: Up to 52 weeks ]
26. Annualized Mild/Moderate and Severe SFI Rates From Baseline Value (Parent Study [NCT05531565]) Through Week 104 [ Time Frame: Up to 104 weeks ]
27. Percentage of Participants With Oral Corticosteroid (OCS) Dose [ Time Frame: Up to 104 weeks ]
28. Percentage of Participants With OCS ≤ 7.5 Milligrams per day (mg/day) [ Time Frame: Up to 104 weeks ]
29. Percentage of Participants With OCS ≤ 5.0 mg/day [ Time Frame: Up to 104 weeks ]
30. Change From Baseline Value (Parent Study [NCT05531565]) in Cutaneous Lupus Erythematosus - Quality of Life (CLE-QoL) at Weeks 52 and 104 [ Time Frame: Baseline, Weeks 52 and 104 ]
31. 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 [ Time Frame: Baseline, Weeks 52 and 104 ]
32. Change From Baseline Value (Parent Study [NCT05531565]) in 36-Item Short Form Survey (SF-36) (acute version) at Weeks 52 and 104 [ Time Frame: Baseline, Weeks 52 and 104 ]
33. Change From Baseline Value (Parent Study [NCT05531565]) in Work Productivity and Activity Impairment (WPAI): Lupus at Weeks 52 and 104 [ Time Frame: Baseline, Weeks 52 and 104 ]
34. Change From Baseline Value (Parent Study [NCT05531565]) in Patient Health Questionnaire-9 (PHQ-9) at Weeks 52 and 104 [ Time Frame: Baseline, Weeks 52 and 104 ]
35. Number of Participants With Clinically Relevant Change From Baseline Value (Parent Study [NCT05531565]) in Standard Laboratory Parameters [ Time Frame: Up to 128 weeks ]
36. Number of Participants With Clinically Relevant Change From Baseline Value (Parent Study [NCT05531565]) in ECG Results [ Time Frame: Up to 104 weeks ]
37. Number of Participants With Anti-BIIB059 Antibodies in Serum [ Time Frame: Up to 128 weeks ]
38. Serum Concentration of Litifilimab [ Time Frame: Pre-dose up to 128 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Michigan

David Fivenson, MD, Dermatology, PLLC

Ann Arbor, Michigan, United States, 48103

Revival Research Institute, LLC

Troy, Michigan, United States, 48084

United States, Texas

Precision Comprehensive Clinical Research Solutions

Grapevine, Texas, United States, 76034

France

Hopital Tenon

Paris, France, 75020

Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 8041

Sweden

Karolinska Universitetssjukhuset - Solna

Solna, Sweden, 17000

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT06044337
• Other Study ID Numbers: 230LE305; 2023-504863-17-00 ( Other Identifier: EU CTIS Number )
• First Posted: September 21, 2023
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases