Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

NCT04058028 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20170588
• Study Type: interventional
• Target: 244
• Locations: 19 countries
• Sites: 147

Brief Summary

The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.

Conditions

Systemic Lupus Erythematosus (SLE)

Keywords

Standard of Care therapies; Oral Corticosteroids; Inmunosuppressants; Immunomodulators; Systemic Lupus Erythematosus; B cell Activating Factor (BAFF); Inducible T cell costimulator ligand (ICOSL)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a SLE Responder Index (SRI-4) Response at Week 52

  SRI-4 response at Week 52 is defined as a ≥ 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score, and no new British Isles Lupus Assessment Group (BILAG) 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3), and no use of more than protocol allowed therapies.

  Week 52

Secondary Outcomes (26)

• Number of Participants With a SRI-4 Response at Week 24

  Week 24

• Number of Participants Who Achieved a BILAG Based Combined Lupus Assessment (BICLA) Response at Week 24

  Week 24

• Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52

  Week 52

• Number of Participants Who Achieved a BICLA Response at Week 52

  Week 52

• Number of Participants Achieving a SRI-4 Response With a Reduction of Oral Corticosteroids (OCS) to ≤ 7.5 mg/Day by Week 44 and Sustained Through Week 52 In Participants With a Baseline OCS Dose ≥ 10 mg/Day

  Up to Week 52

Study Arms (4)

Rozibafusp Alfa, Dose A

EXPERIMENTAL

Investigational product solution in vial

Drug: Rozibafusp Alfa

Rozibafusp Alfa, Dose B

EXPERIMENTAL

Investigational product solution in vial

Drug: Rozibafusp Alfa

Rozibafusp Alfa, Dose C

EXPERIMENTAL

Investigational product solution in vial

Drug: Rozibafusp Alfa

Placebo for Rozibafusp Alfa

PLACEBO COMPARATOR

Placebo Investigational product solution in vial

Drug: Placebo for Rozibafusp Alfa

Interventions

Rozibafusp Alfa DRUG

Rozibafusp Alfa will be presented in 5 mL glass vial

Rozibafusp Alfa, Dose A; Rozibafusp Alfa, Dose B; Rozibafusp Alfa, Dose C

Placebo for Rozibafusp Alfa DRUG

Placebo for Rozibafusp Alfa will be presented in 5 mL glass vial

Placebo for Rozibafusp Alfa

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Age ≥ 18 years to ≤ 75 years at screening visit.
• Fulfills classification criteria for SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE (Aringer et al, 2019), with antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening.
• Additional protocol-specific rules are applied at screening and throughout the study, as follows:
• Arthritis: Arthritis (at least 3 tender and swollen joints) must involve joints in the hands or wrists for the hSLEDAI scoring.
• Alopecia: Subjects should have hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia ≥ 2.
• Oral ulcers: Ulcers location and appearance must be documented by the investigator.
• Scleritis and Episcleritis: the presence of stable SLE-related scleritis and episcleritis must be documented by an ophthalmologist and other causes excluded.
• Renal: subjects with urine protein/creatinine ratio \< 3000 mg/g (or equivalent method) in a clear catch spot urine sample can enroll and be scored in the hSLEDAI, provided the subject has a clinical hSLEDAI ≥ 4 and did not receive induction treatment for nephritis within the last year.
• Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI.
• Unless there is a documented intolerance, subjects must be taking:
• Only 1 of the following SLE treatments: anti-malarial (hydroxychloroquine, chloroquine, or quinacrine), azathioprine, methotrexate, leflunomide, mycophenolate mofetil/acid mycophenolic, or dapsone.
• 2 of the above-mentioned SLE treatments in which 1 must be anti-malarial (hydroxychloroquine, chloroquine, or quinacrine).
• Treatment should be taken for ≥ 12 weeks prior to screening and must be a stable dose for ≥ 8 weeks prior to screening.
• For subjects taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit for ≥ 2 weeks prior to screening visit.

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply:
• Disease Related
• Urine protein creatinine ratio ≥ 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit.
• Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.

Sponsors & Collaborators

• Amgen: lead

Study Sites (147)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Imaging Endpoints

Scottsdale, Arizona, 85258, United States

Location

Medvin Clinical Research

Covina, California, 91723, United States

Location

Southern California Permanente Medical Group

Fontana, California, 92335, United States

Location

University of California San Diego

La Jolla, California, 92037, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University Hospitals and Clinics

Palo Alto, California, 94304, United States

Location

TriWest Research Associates

San Diego, California, 92108, United States

Location

University of Colorado Denver

Aurora, Colorado, 80010, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Centre for Rheumatology Immunology and Arthritis

Fort Lauderdale, Florida, 33309, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Lakes Research LLC

Miami Lakes, Florida, 33014, United States

Location

Heuer Medical Doctor Research LLC

Orlando, Florida, 32819, United States

Location

Southwest Florida Clinical Research Center

Tampa, Florida, 33609, United States

Location

AdventHealth Medical Group

Tampa, Florida, 33613, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30318, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Clinic of Robert Hozman, MD - Clinical Investigational Specialists, Inc

Skokie, Illinois, 60076, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland School of Medicine Division of Rheumatology

Baltimore, Maryland, 21201, United States

Location

Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

New York University Langone Orthopedic Center

New York, New York, 10016, United States

Location

Hospital For Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Joint and Muscle Research Institute

Charlotte, North Carolina, 28204, United States

Location

DJL Clinical Research PLLC

Charlotte, North Carolina, 28210, United States

Location

Arthritis and Rheumatology Center of Oklahoma PLLC

Oklahoma City, Oklahoma, 73102, United States

Location

The Oklahoma Center for Arthritis Therapy and Research Inc

Tulsa, Oklahoma, 74104, United States

Location

Penn State Milton South Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Articularis Healthcare Group Inc dba Low Country Rheumatology

Summerville, South Carolina, 29486, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Austin Regional Clinic Specialty Research

Austin, Texas, 78731, United States

Location

Trinity Universal Research Associates, Inc

Carrollton, Texas, 75007, United States

Location

Rheumatic Disease Clinical Research Center LLC

Houston, Texas, 77004, United States

Location

Southwest Rheumatology

Mesquite, Texas, 75150, United States

Location

Dom Centro de Reumatologia

CABA, Buenos Aires, C1111AAJ, Argentina

Location

Fundacion Respirar - Centro Medico Dra De Salvo

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1426ABP, Argentina

Location

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, B1878GEG, Argentina

Location

Instituto Medico de Alta Complejidad San Isidro

San Isidro, Buenos Aires, 1642, Argentina

Location

Hospital Militar Central - Cirujano Mayor Dr Cosme Argerich

Buenos Aires, Distrito Federal, C1426BOR, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

Clinical Mayo - Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L

San Miguel de Tucumán, Tucumán Province, T4000, Argentina

Location

CER San Juan - Centro Polivalente de Asistencia e Investigacion Clinica

San Juan, 5400, Argentina

Location

Holdsworth House Medical Practice

Sydney, New South Wales, 2010, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Multiprofile Hospital for Active Treatment Trimontium OOD

Plovdiv, 4000, Bulgaria

Location

University Multiprofile Hospital for Active Treatment - Kaspela EOOD

Plovdiv, 4002, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, 4002, Bulgaria

Location

Medical Center Excelsior OOD

Sofia, 1407, Bulgaria

Location

Medical Center Academy EOOD

Sofia, 1612, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD

Sofia, 1612, Bulgaria

Location

Medical Centre Synexus Sofia EOOD

Sofia, 1784, Bulgaria

Location

Medical Centre Synexus Sofia EOOD - Branch Stara Zagora

Stara Zagora, 6003, Bulgaria

Location

University of Calgary Cumming School of Medicine

Calgary, Alberta, T2N 4N1, Canada

Location

Shared Health Inc. operating the Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R3A 1M4, Canada

Location

Groupe de recherche en maladies osseuses Incorporated

Québec, Quebec, G1V 3M7, Canada

Location

Synexus Czech sro

Prague, 120 00, Czechia

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin

Bordeaux, 33076, France

Location

CHU Hôpital Côte de Nacre

Caen, 14033, France

Location

Centre Hospitalier Universitaire Dijon Bourgogne - Hopital Francois Mitterrand

Dijon, 21079, France

Location

Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Hopital Pitie-Salpetriere

Paris, 75013, France

Location

Centre Hospitalier Universitaire de Reims - Hopital Robert Debre

Reims, 51092, France

Location

Centre Hospitalier Universitaire de Strasbourg - Nouvel hopital civil

Strasbourg, 67091, France

Location

Centre Hospitalier Universitaire de Toulouse - Hopital Purpan

Toulouse, 31059, France

Location

Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil

Toulouse, 31059, France

Location

Johannes Gutenberg Universitaet Mainz

Bad Kreuznach, 55543, Germany

Location

Universitätsklinikum Leipzig AöR

Leipzig, 04103, Germany

Location

Laiko General Hospital

Athens, 11527, Greece

Location

Attiko Hospital

Athens, 12462, Greece

Location

University Hospital of Heraklion

Heraklion, 71500, Greece

Location

General University Hospital of Patras Panagia i Voithia

Pátrai, 26504, Greece

Location

Tuen Mun Hospital

New Territories, Hong Kong

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz

Gyula, 5700, Hungary

Location

Vita Verum Medical Bt

Székesfehérvár, 8000, Hungary

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano MI, 20089, Italy

Location

National Hospital Organization Chibahigashi National Hospital

Chiba, Chiba, 260-8712, Japan

Location

Juntendo University Urayasu Hospital

Urayasu-shi, Chiba, 279-0021, Japan

Location

Hospital of the University of Occupational and Environmental Health Japan

Kitakyushu-shi, Fukuoka, 807-8556, Japan

Location

Gifu University Hospital

Gifu, Gifu, 501-1194, Japan

Location

Sapporo City General Hospital

Sapporo, Hokkaido, 060-8604, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

National University Corporation Tohoku University Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Shinshu University Hospital

Matsumoto-shi, Nagano, 390-8621, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

National Hospital Organization Nagasaki Medical Center

Omura-shi, Nagasaki, 856-8562, Japan

Location

Sasebo Chuo Hospital

Sasebo-shi, Nagasaki, 857-1195, Japan

Location

Kurashiki Medical Clinic

Kurashiki-shi, Okayama-ken, 710-8522, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Seirei Hamamatsu General Hospital

Hamamatsu, Shizuoka, 430-8558, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

St Lukes International Hospital

Chuo-ku, Tokyo, 104-8560, Japan

Location

National Hospital Organization Tokyo Medical Center

Meguro-ku, Tokyo, 152-8902, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Centro Medico del Angel SC

Mexicali, Baja California Norte, 21100, Mexico

Location

Centro de Investigacion en Artritis y Osteoporosis SC

Mexicalli, Baja California Norte, 21200, Mexico

Location

Morales Vargas Centro de Investigacion SC

León, Guanajuato, 37000, Mexico

Location

Centro Integral en Reumatologia SA de CV

Guadalajara, Jalisco, 44160, Mexico

Location

Centro Peninsular de Investigación Clínica

Mérida, Yucatán, 97000, Mexico

Location

Centro Mexicano de Desarrollo de Estudios Clinicos

Mexico City, 06100, Mexico

Location

Synexus Polska Spzoo

Gdansk, 80-382, Poland

Location

Synexus Polska Spzoo

Gdynia, 81-537, Poland

Location

Synexus Polska Spzoo

Katowice, 40-040, Poland

Location

Silmedic Spzoo

Katowice, 40-282, Poland

Location

Tomed Tomasz Miszalski-Jamka Centrum Medyczne

Krakow, 31-209, Poland

Location

Synexus Polska Spzoo

Lodz, 90-127, Poland

Location

Somed cr

Lodz, 90-368, Poland

Location

1 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej

Lublin, 20-049, Poland

Location

Clinical Best Solutions Spolka z ograniczona odpowiedzialnoscia Spolka komandytowa

Lublin, 20-078, Poland

Location

Synexus Polska Spzoo

Poznan, 60-702, Poland

Location

Sanus Szpital Specjalistyczny Spzoo

Stalowa Wola, 37-450, Poland

Location

SOMED CR

Warsaw, 01-737, Poland

Location

Synexus Polska Spolka z ograniczona odpowiedzialnoscia

Warsaw, 02-672, Poland

Location

Futuremeds spolka z ograniczona odpowiedzialnoscia

Wroclaw, 50-088, Poland

Location

Synexus Polska Spzoo

Wroclaw, 50-381, Poland

Location

Hospital Garcia de Orta, EPE

Almada, 2801-951, Portugal

Location

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Centro Hospitalar do Porto EPE - Hospital de Santo Antonio

Porto, 4099-001, Portugal

Location

Centro Hospitalar Universtario de Sao Joao, EPE

Porto, 4200-319, Portugal

Location

Limited liability company Scientific Research Medical Complex Your Health

Kazan', 420097, Russia

Location

LLC Medical Center Maksimum Zdorovia

Kemerovo, 650066, Russia

Location

LLC Medical center Revma Med

Kemerovo, 650070, Russia

Location

FSBSI SRI of Rheumatology na V A Nasonova

Moscow, 115522, Russia

Location

LLC Center of medicine Healthy family

Novosibirsk, 630061, Russia

Location

LLC Center of general medicine

Novosibirsk, 630091, Russia

Location

LLC Medical Sanitary Unit №157

Saint Petersburg, 196066, Russia

Location

State Budget Medical Institution Sverdlovsk Regional Clinical Hospital N1

Yekaterinburg, 620102, Russia

Location

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Ewha Womans University Mokdong Hospital

Seoul, 07985, South Korea

Location

Ajou University Hospital

Suwon-si, Gyeonggi-do, 443-380, South Korea

Location

Hospital Infanta Luisa

Seville, Andalusia, 41010, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, Galicia, 15006, Spain

Location

Related Publications (2)

• Garces S, Karis E, Merrill JT, Askanase AD, Kalunian K, Mo M, Milmont CE. Improving resource utilisation in SLE drug development through innovative trial design. Lupus Sci Med. 2023 Jul;10(2):e000890. doi: 10.1136/lupus-2022-000890.

  PMID: 37491104 DERIVED

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

  PMID: 33687069 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

rozibafusp alfa

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including OCS, immunosuppressants, and immunomodulators. Subjects will be randomized to receive placebo or 1 of 3 doses of Rozibafusp Alfa with the last dose at week 50. Treatment will be administered every 2 weeks (Q2W). All subjects will be required to complete a 16-week follow-up period after the 52-week treatment period. The first interim analysis (IA) will be executed after the first 40 enrolled subjects have had the opportunity to complete the week 24 assessment. Additional IAs may be executed after approximately every 32 newly enrolled subjects have had the opportunity to complete the week 24 assessment. The last IA will occur when all subjects have had the opportunity to complete the week 24 assessment.

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 15, 2019
• Study Start: February 19, 2020
• Primary Completion: July 25, 2023
• Study Completion: July 25, 2023
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

PL (15); PT (5); FR (9); AU (2); GR (4); HU (3); BU (8); CA (3); RU (8); US (39); DE (2); HK (1); KR (4); ES (3); ME (6); CZ (2); AR (8); IT (4); JP (21)