Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

— Tulip SC  

Official title:

A Multicentre, Randomised, Double-Blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04877691
• Other study ID #: D3465C00001
• Secondary ID: SZA644002020-004
• Status: Recruiting
• Phase: Phase 3
• Start date: June 8, 2021
• Est. completion date: December 11, 2026

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is evaluating the efficacy and safety of SC antifrolumab in adult patients with moderate -to-severe SLE despite receiving standard therapy

Description:

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral glucocorticoids, antimalarial, and/or immunosuppressants. The study will be performed in adult participants of 18 to 70 years of age.

Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed subcutaneous dose of anifrolumab or placebo administered once weekly via an accessorized prefilled syringe and with the primary endpoint evaluated at Week 52. Subjects who complete Week 52 may enter into open-label extension (OLE). All patients who enter the OLE Period will receive a fixed subcutaneous dose of anifrolumab for up to 52 weeks. Study intervention will be administered SC via an accessorised prefilled syringe (aPFS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: December 11, 2026
• Est. primary completion date: August 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for = 24 weeks prior to signing the ICF

2. To be eligible a patient must have SLEDAI-2K = 6 points and "Clinical" SLEDAI-2K score =4 points at screening

3. BILAG2004 with at least 1 of the following:

1. BILAG2004 level A disease in = 1 organ system

2. BILAG2004 level B disease in = 2 organ systems

4. Physician's Global Assessment (PGA) score = 1.0 on a 0 to 3 VAS at Screening

5. Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,

6. Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations.

Exclusion Criteria:

7. Active severe or unstable neuropsychiatric SLE

8. Active severe SLE-driven renal disease

9. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.

10. History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks).

11. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.

12. At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody

13. Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),

14. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.

15. History of cancer, apart from:

1. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy = 3 months prior to Week 0 (Day 1)

2. Cervical cancer in situ treated with apparent success with curative therapy = 1 year prior to Week 0 (Day 1).

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Medi-546
Patients will have IP administered or will self-administer IP under supervision by site staff at Week 0 and Week 1 and, for patients participating in the OLE period, at Week 52. For weekly doses coinciding with subsequent on-site visits, patients will also have IP administered or will self-administer IP under supervision by site staff, and in addition will receive a set of kits (including back-up kits) for at-home administration.
• Placebo
Solution for injection in aPFS

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	La Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Pergamino
Argentina	Research Site	Quilmes
Argentina	Research Site	Rosario
Argentina	Research Site	Salta
Argentina	Research Site	San Isidro
Argentina	Research Site	San Juan
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Miguel de Tucuman
Bulgaria	Research Site	Kardzhali
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sevlievo
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Chile	Research Site	Osorno
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Valdivia
Colombia	Research Site	Barranquilla
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bucaramanga
Colombia	Research Site	Bucaramanga
Colombia	Research Site	Chia
Colombia	Research Site	Medellin
Colombia	Research Site	Monteria
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Kirchheim
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Tuebingen
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyula
Hungary	Research Site	Szekesfehervar
Hungary	Research Site	Veszprem
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Meguro-ku
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya
Japan	Research Site	Nagoya-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sasebo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Tsukuba-shi
Mexico	Research Site	Chihuahua
Mexico	Research Site	Culiacan
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Merida
Mexico	Research Site	Merida
Mexico	Research Site	Mexicali
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Davao City
Philippines	Research Site	Iloilo
Philippines	Research Site	Lipa City
Philippines	Research Site	Makati City
Philippines	Research Site	Quezon City
Poland	Research Site	Katowice
Poland	Research Site	Koscian
Poland	Research Site	Krakow
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Nowa Sól
Poland	Research Site	Ustron
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Thailand	Research Site	Muang
Thailand	Research Site	Rachathewi
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Kryvyi Rih
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Odesa
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Doncaster
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Harlow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Leytonstone
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Wigan
United States	Research Site	Anniston	Alabama
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Brandon	Florida
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Decatur	Georgia
United States	Research Site	Denver	Colorado
United States	Research Site	El Cajon	California
United States	Research Site	El Paso	Texas
United States	Research Site	Flint	Michigan
United States	Research Site	Fullerton	California
United States	Research Site	Grapevine	Texas
United States	Research Site	Hemet	California
United States	Research Site	Hialeah	Florida
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	La Mesa	California
United States	Research Site	Lansing	Michigan
United States	Research Site	Las Cruces	New Mexico
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Los Angeles	California
United States	Research Site	Manhasset	New York
United States	Research Site	Memphis	Tennessee
United States	Research Site	Menifee	California
United States	Research Site	Miami	Florida
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Paradise Valley	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Potsdam	New York
United States	Research Site	Reading	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Upland	California
United States	Research Site	Voorhees	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Chile,  Colombia,  Germany,  Hungary,  Japan,  Mexico,  Peru,  Philippines,  Poland,  Russian Federation,  Spain,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Event Overview	Overview of AEs, SAEs and AESIs	Up to 2 years 4 months
Primary	British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response	BICLA response is a composite binary endpoint whereby responders are defined by meeting all of the following criteria: Improvement from baseline in disease activity as measured by BILAG-2004. Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, where worsening is defined as = 1 new BILAG-2004 A or = 2 new BILAG 2004 B.; No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of > 0 points in SLEDAI-2K.; No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase = 0.30 points on a 3-point PGA VAS.	At week 52
Secondary	Time to first BICLA response sustained through Week 52	Time from first dose to first BICLA response that is consecutively maintained through Week 52	Baseline through to Week 52
Secondary	BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS)	Response is defined by being a BICLA responder at Week 52 and having maintained low (or reduced) OCS use through Week 52. Maintained OCS use is defined as follows: If baseline OCS = 10 mg/day an OCS dose of = 7.5 mg/day prednisone or equivalent must be achieved by Week 40 and an OCS dose = 7.5 mg/day prednisone or equivalent must be maintained from Week 40 to Week 52.; If baseline OCS < 10 mg/day, OCS dose at Week 40 must be less than or equal to OCS dose at baseline, with no increase from Week 40 OCS dose between Week 40 and Week 52.	At week 52
Secondary	Time to flare	Flare defined as either 1 or more BILAG 2004 A or 2 or more BILAG 2004 B compared to previous visit	Baseline through to Week 52
Secondary	Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS =10 mg/day.	Achieving maintained OCS reduction through Week 52 is defined by meeting all of the following criteria: Achieve an OCS dose of = 7.5 mg/day prednisone or equivalent by Week 40; Maintain an OCS dose = 7.5 mg/day prednisone or equivalent from Week 40 to Week 52; No discontinuation of investigational product; No use of restricted medications beyond the protocol allowed threshold before assessment	At week 52
Secondary	Annualized flare rate	Flare defined as either 1 or more BILAG 2004 or 2 or more BILAG2004 B compared to previous visit	Baseline through to Week 52
Secondary	SRI4	Proportion of patients achieving a SRI of = 4 (SRI[4]) response at Week 52, defined by meeting all of the following criteria: Reduction from baseline of = 4 points in the SLEDAI-2K No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG 2004 B items compared to baseline using BILAG-2004 No worsening from baseline in the patients' lupus disease activity, where worsening is defined by an increase = 0.30 points on a 3-point PGA VAS.	At week 52