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

Systemic Lupus Erythematosus (SLE) Clinical Trial

Official title:

A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04058028
• Other study ID #: 20170588
• Status: Completed
• Phase: Phase 2
• Start date: February 19, 2020
• Est. completion date: July 25, 2023

Study information

• Verified date: March 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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 oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: July 25, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria Screening Visit:

• 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.

• Hybrid SLEDAI score = 6 points with a "Clinical" hSLEDAI score = 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.

• 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.

OR

• 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.

Exclusion Criteria Screening Visit

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

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

Locations

Country	Name	City	State
Argentina	Hospital Militar Central - Cirujano Mayor Dr Cosme Argerich	Buenos Aires	Distrito Federal
Argentina	Dom Centro de Reumatologia	Caba	Buenos Aires
Argentina	Fundacion Respirar - Centro Medico Dra De Salvo	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires
Argentina	Instituto Medico de Alta Complejidad San Isidro	San Isidro	Buenos Aires
Argentina	CER San Juan - Centro Polivalente de Asistencia e Investigacion Clinica	San Juan
Argentina	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman
Argentina	Clinical Mayo - Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L	San Miguel de Tucuman	Tucuman
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Bulgaria	Multiprofile Hospital for Active Treatment Trimontium OOD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment - Kaspela EOOD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv
Bulgaria	Medical Center Academy EOOD	Sofia
Bulgaria	Medical Center Excelsior OOD	Sofia
Bulgaria	Medical Centre Synexus Sofia EOOD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD	Sofia
Bulgaria	Medical Centre Synexus Sofia EOOD - Branch Stara Zagora	Stara Zagora
Canada	University of Calgary Cumming School of Medicine	Calgary	Alberta
Canada	Groupe de recherche en maladies osseuses Incorporated	Quebec
Canada	Shared Health Inc. operating the Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Czechia	Revmatologicky ustav	Praha 2
Czechia	Synexus Czech sro	Praha 2
France	Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin	Bordeaux
France	CHU Hôpital Côte de Nacre	Caen Cedex 9
France	Centre Hospitalier Universitaire Dijon Bourgogne - Hopital Francois Mitterrand	Dijon Cedex
France	Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez	Lille cedex 01
France	Hopital Pitie-Salpetriere	Paris
France	Centre Hospitalier Universitaire de Reims - Hopital Robert Debre	Reims Cedex
France	Centre Hospitalier Universitaire de Strasbourg - Nouvel hopital civil	Strasbourg
France	Centre Hospitalier Universitaire de Toulouse - Hopital Purpan	Toulouse
France	Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil	Toulouse Cedex 9
Germany	Johannes Gutenberg Universitaet Mainz	Bad Kreuznach
Germany	Universitätsklinikum Leipzig AöR	Leipzig
Greece	Attiko Hospital	Athens
Greece	Laiko General Hospital	Athens
Greece	University Hospital of Heraklion	Heraklion
Greece	General University Hospital of Patras Panagia i Voithia	Patra
Hong Kong	Tuen Mun Hospital	New Territories
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz	Gyula
Hungary	Vita Verum Medical Bt	Szekesfehervar
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	IRCCS Istituto Clinico Humanitas	Rozzano MI
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
Japan	National Hospital Organization Chibahigashi National Hospital	Chiba-shi	Chiba
Japan	St Lukes International Hospital	Chuo-ku	Tokyo
Japan	Gifu University Hospital	Gifu-shi	Gifu
Japan	Seirei Hamamatsu General Hospital	Hamamatsu-shi	Shizuoka
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa
Japan	Hospital of the University of Occupational and Environmental Health Japan	Kitakyushu-shi	Fukuoka
Japan	Kobe University Hospital	Kobe-shi	Hyogo
Japan	Kurashiki Medical Clinic	Kurashiki-shi	Okayama
Japan	Shinshu University Hospital	Matsumoto-shi	Nagano
Japan	National Hospital Organization Tokyo Medical Center	Meguro-ku	Tokyo
Japan	Nagasaki University Hospital	Nagasaki-shi	Nagasaki
Japan	Okayama University Hospital	Okayama-shi	Okayama
Japan	National Hospital Organization Nagasaki Medical Center	Omura-shi	Nagasaki
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo City General Hospital	Sapporo-shi	Hokkaido
Japan	Sasebo Chuo Hospital	Sasebo-shi	Nagasaki
Japan	National University Corporation Tohoku University Tohoku University Hospital	Sendai-shi	Miyagi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Juntendo University Urayasu Hospital	Urayasu-shi	Chiba
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si, Gyeonggi-do
Mexico	Centro Mexicano de Desarrollo de Estudios Clinicos	Ciudad de Mexico
Mexico	Centro Integral en Reumatologia SA de CV	Guadalajara	Jalisco
Mexico	Morales Vargas Centro de Investigacion SC	Leon	Guanajuato
Mexico	Centro Peninsular de Investigación Clínica	Merida	Yucatán
Mexico	Centro Medico del Angel SC	Mexicali	Baja California Norte
Mexico	Centro de Investigacion en Artritis y Osteoporosis SC	Mexicalli	Baja California Norte
Poland	Synexus Polska Spzoo	Gdansk
Poland	Synexus Polska Spzoo	Gdynia
Poland	Silmedic Spzoo	Katowice
Poland	Synexus Polska Spzoo	Katowice
Poland	Tomed Tomasz Miszalski-Jamka Centrum Medyczne	Krakow
Poland	Somed cr	Lodz
Poland	Synexus Polska Spzoo	Lodz
Poland	1 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Lublin
Poland	Clinical Best Solutions Spolka z ograniczona odpowiedzialnoscia Spolka komandytowa	Lublin
Poland	Synexus Polska Spzoo	Poznan
Poland	Sanus Szpital Specjalistyczny Spzoo	Stalowa Wola
Poland	SOMED CR	Warszawa
Poland	Synexus Polska Spolka z ograniczona odpowiedzialnoscia	Warszawa
Poland	Futuremeds spolka z ograniczona odpowiedzialnoscia	Wroclaw
Poland	Synexus Polska Spzoo	Wroclaw
Portugal	Hospital Garcia de Orta, EPE	Almada
Portugal	Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz	Lisboa
Portugal	Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar do Porto EPE - Hospital de Santo Antonio	Porto
Portugal	Centro Hospitalar Universtario de Sao Joao, EPE	Porto
Russian Federation	State Budget Medical Institution Sverdlovsk Regional Clinical Hospital N1	Ekaterinburg
Russian Federation	Limited liability company Scientific Research Medical Complex Your Health	Kazan
Russian Federation	LLC Medical Center Maksimum Zdorovia	Kemerovo
Russian Federation	LLC Medical center Revma Med	Kemerovo
Russian Federation	FSBSI SRI of Rheumatology na V A Nasonova	Moscow
Russian Federation	LLC Center of general medicine	Novosibirsk
Russian Federation	LLC Center of medicine Healthy family	Novosibirsk
Russian Federation	LLC Medical Sanitary Unit ?157	Saint Petersburg
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña	Galicia
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Hospital Infanta Luisa	Sevilla	Andalucía
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Austin Regional Clinic Specialty Research	Austin	Texas
United States	University of Maryland School of Medicine Division of Rheumatology	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Trinity Universal Research Associates, Inc	Carrollton	Texas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	DJL Clinical Research PLLC	Charlotte	North Carolina
United States	Joint and Muscle Research Institute	Charlotte	North Carolina
United States	Medvin Clinical Research	Covina	California
United States	Southern California Permanente Medical Group	Fontana	California
United States	Centre for Rheumatology Immunology and Arthritis	Fort Lauderdale	Florida
United States	University of Florida	Gainesville	Florida
United States	Penn State Milton South Hershey Medical Center	Hershey	Pennsylvania
United States	Rheumatic Disease Clinical Research Center LLC	Houston	Texas
United States	University of California San Diego	La Jolla	California
United States	University of California Los Angeles	Los Angeles	California
United States	Feinstein Institute for Medical Research	Manhasset	New York
United States	Southwest Rheumatology	Mesquite	Texas
United States	Lakes Research LLC	Miami Lakes	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Hospital For Special Surgery	New York	New York
United States	New York University Langone Orthopedic Center	New York	New York
United States	Arthritis and Rheumatology Center of Oklahoma PLLC	Oklahoma City	Oklahoma
United States	Heuer Medical Doctor Research LLC	Orlando	Florida
United States	Stanford University Hospitals and Clinics	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	TriWest Research Associates	San Diego	California
United States	Imaging Endpoints	Scottsdale	Arizona
United States	Clinic of Robert Hozman, MD - Clinical Investigational Specialists, Inc	Skokie	Illinois
United States	Articularis Healthcare Group Inc dba Low Country Rheumatology	Summerville	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York
United States	AdventHealth Medical Group	Tampa	Florida
United States	Southwest Florida Clinical Research Center	Tampa	Florida
United States	The Oklahoma Center for Arthritis Therapy and Research Inc	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Russian Federation,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 52	SRI-4 response at Week 52 is defined as a greater than or equal to 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	Percent of patients achieving a SRI-4 response at week 24	SRI-4 response at Week 24 is defined as a greater than or equal to 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 24
Secondary	Percent of patients achieving Lupus Low Disease Activity State (LLDAS) at week 52	LLDAS response at week 52 is defined as a hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score = 4 with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, and fever) and no haemolytic anaemia or gastrointestinal activity; no new findings of lupus disease activity compared with the previous assessment; = 1-point in Physician Global Assessment (PGA) (scale 0 to 3) current prednisolone-equivalent dosage = 7.5 mg/day; and standard maintenance dosages of immunosuppressive drugs and approved biologics.	Week 52
Secondary	Percent of patients achieving The British Isles Lupus Assessment Group (BILAG) based Combined Lupus Assessment (BICLA) index responses	BICLA response is defined as at least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry (eg, all A [severe disease] domain scores falling to B [moderate], C [mild], or D [no activity], and all B domain scores falling to C or D); no new BILAG 2004 A domain score and no > than 1 new BILAG 2004 B domain scores compared with baseline; no worsening of the hSLEDAI score from baseline; no = 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3); and no use of more than protocol-allowed therapies; and no initiation of non-protocol treatment for SLE.	Week 24 and Week 52
Secondary	SRI-4 at week 52 with reduction of OCS to less than or equal to 7.5 mg/day by week 44 and sustained through week 52 in subjects with a baseline OCS dose = 10 mg/day	To evaluate the efficacy of Rozibafusp Alfa with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.	Week 52
Secondary	Annualized moderate and severe flare rate	Measured by SELENA-SLEDAI Flare Index.	52 weeks
Secondary	Annualized severe flare rate	Measured by SELENA-SLEDAI Flare Index.	52 weeks
Secondary	Annualized flare rate	Measured by BILAG score designation of "worse" or "new" resulting in a B score in = 2 organs or an A score in = 1 organ) over 52 weeks.	52 weeks
Secondary	Total tender and swollen joint count (limited to hands and wrists): = 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with = 6 tender and swollen joints in the hands and wrists at baseline	A joint count will be used to evaluate the effect of Rozibafusp Alfa on additional SLE efficacy endpoints.	Baseline, Week 12, 24, 36, and 52
Secondary	Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) activity score = 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with a CLASI activity score = 8 at baseline	To evaluate the effect of Rozibafusp Alfa on additional SLE efficacy endpoints	Baseline, Week 12, 24, 36, and 52
Secondary	Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS-Fatigue SF7A) score change from baseline	To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes	Baseline, Week 12, 24, 36, 44 and 52
Secondary	Medical Outcomes Short Form 36 version 2 Questionnaire (SF-36v2) physical component score change from baseline	To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes	Baseline, Week 12, 24, 36, 44 and 52
Secondary	Medical Outcomes Short Form 36 version 2 Questionnaire (SF-36v2) mental component score individual domains change from baseline	To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes	Baseline, Week 12, 24, 36, 44 and 52
Secondary	Lupus Quality of Life (QoL) score and change from baseline	To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes	Baseline, Week 12, 24, 36, 44 and 52
Secondary	Patient Global Assessment (PtGA) score change from baseline	This is an 11-point NRS with 0 indicating lowest disease and 10 highest disease activity.	Baseline, Week 12, 24, 36, 44 and 52
Secondary	Patient incidence of Treatment-Emergent Adverse Events	To characterize the safety of Rozibafusp Alfa.	52 weeks
Secondary	Patient incidence of Serious adverse events	To characterize the safety of Rozibafusp Alfa.	52 weeks
Secondary	Number of patients with significant changes in laboratory values	To characterize the safety of Rozibafusp Alfa.	52 weeks
Secondary	Number of patients with significant changes in vital signs	To characterize the safety of Rozibafusp Alfa.	52 weeks
Secondary	Serum Rozibafusp Alfa trough concentrations	To characterize the pharmacokinetics (PK) of Rozibafusp Alfa	52 Weeks
Secondary	Rozibafusp Alfa terminal elimination half-life, if possible	To characterize the pharmacokinetics (PK) of Rozibafusp Alfa	52 weeks

External Links

•   AmgenTrials clinical trials website