Clinical trial NCT04925934: Study of VIB7734 for the Treatment of Moderate to Severely Active SLE
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-06-14
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel-arm study
Primary purpose: TREATMENT

Brief summary: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus in approximately 195 participants. The study duration will be 48 weeks, with a safety follow-up through week 56.There will be 3 parallel arms - 2 active treatment and 1 placebo.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years to ≤ 70 years
* Willing and able to understand and provide written informed consent.
* Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for SLE
* Disease duration of at least 6 months
* Active SLE as indicated by presence of all the following:

  1. SLEDAI-2K total score ≥ 6 at Screening, excluding fever, SLE headache, or organic brain syndrome.
  2. SLEDAI-2K total score ≥ 4, excluding points attributable to any urine or laboratory results, immunologic measures, fever, SLE headache, or organic brain syndrome at Screening and Baseline (Day 1).
  3. At least one of the following BILAG 2004 Index levels of disease at Screening:
* BILAG A disease in ≥ 1 organ system
* BILAG B disease in ≥ 2 organ systems d. PGA score ≥ 1 on a 0 to 3 visual analog scale (VAS) at Screening

Have at least one of the following at Screening per central lab:

* ANA ≥ 1:80
* Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results)
* Anti-Smith antibodies elevated to above normal (ie, positive results) Ongoing treatment for SLE

  1. Treatment with one or more disease-modifying anti-rheumatic drug (DMARD) or immunosuppressive medication: Any of the following medications each administered at conventional anti-rheumatic doses for treatment of SLE for at least 12 weeks before Screening (unless discontinued or dose adjusted for documented drug-related toxicity or size/weight), and at a stable dose (including route of administration) for a minimum of 8 weeks prior to Screening and maintained through Baseline (Day 1):
  2. Treatment with OGC monotherapy (without the concomitant use of DMARDs or immunosuppressants):

     * Average daily dose of PO prednisone ≥ 10 mg but ≤ 40 mg (or prednisone equivalent) for a minimum of 4 weeks prior to Screening and a stable dose for minimum of 2 weeks prior to Screening. The dose of OGC must be kept for a minimum of 2 weeks prior to Randomization. Daily dosing or alternate day dosing of PO prednisone or equivalent is allowed.
* Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Randomization.
* Non-sterilized male participants who are sexually active with a woman partner of childbearing potential must agree to use a condom with spermicide from Randomization and until 3 months (approximately 5 half-lives) after receipt of the last dose.

Exclusion Criteria:

* Any condition that, in the opinion of the Investigator, or the Sponsor/Central Review Committee, would interfere with the evaluation of the IP or interpretation of participant safety or study results (including borderline disease activity)
* History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or a previous mAb or human Ig therapy
* Active LN or active severe or unstable neuropsychiatric SLE
* Current diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or rheumatic (overlap) syndrome
* Participation in another clinical study with an investigational drug within 4 weeks before Day 1
* Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the ICF through 6 months after receiving the last dose of IP
* Major surgery within 8 weeks prior to Screening or elective surgery planned from Screening through Day 393.
* Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks before Screening
* Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection
* Hepatitis B, Hepatitis C, active TB, any severe herpes infection, clinically active infection, or opportunistic infection
* History of clinically significant cardiac disease including unstable angina; and/or myocardial infarction and/or congestive heart failure within 6 months prior to Randomization.
* History of cancer within the past 5 years except, in situ carcinoma of the cervix, cutaneous basal cell or squamous cell carcinoma with curative therapy.
* Receipt of a live-attenuated vaccine within 4 weeks before Day 1 Administration of inactivated (killed) vaccines is acceptable
* The use of immunosuppressants, biologics and DMARDS within the protocol defined washout periods

Primary outcomes:
measure: Number of Participants Achieving a BILAG-2004 Index-based Combined Lupus Assessment (BICLA) Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score ≥ 10 at Baseline Achieving ≥ 50% Reduction From Baseline in CLASI-A Score at Week 12
timeFrame: Week 12
measure: Number of Participants Achieving an SLE Responder Index (SRI)-4 Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48
timeFrame: Week 48
measure: Number of Participants With an OGC Dose ≥ 10 mg/Day of Prednisone or Equivalent at Baseline Who Maintained an OGC Dose ≤ 7.5 mg/Day From Week 36 Through Week 48
timeFrame: Week 36 up to Week 48
measure: Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48
timeFrame: Week 48
measure: Serum Concentration of Daxdilimab
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48
measure: Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab
timeFrame: Baseline to Week 56
measure: Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 32, Week 36, Week 44, Week 48, Week 52, Week 56
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Week 56
measure: Number of Participants Who Experienced AEs of Special Interest (AESI)
timeFrame: Up to Week 56
Other outcomes:
Locations:
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials Incorporated
state: California
city: Clearwater
country: United States
facility: Clinical Research of West Florida Inc - Clearwater
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida Inc - Tampa
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Lexington
country: United States
facility: Bluegrass Community Research Inc
state: Kentucky
city: Brooklyn
country: United States
facility: NYU Langone Ambulatory Care Brooklyn Heights
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute For Medical Research
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Charlotte
country: United States
facility: DJL Clinical Research
state: North Carolina
city: Middleburg Heights
country: United States
facility: Paramount Medical Research and Consulting LLC
state: Ohio
city: Austin
country: United States
facility: Tekton Research Inc
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research, LLC
state: Texas
city: Danville
country: United States
facility: Spectrum Medical, Inc
state: Virginia
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Consultorios Médicos Dr. Doreski
state: Buenos Aires
city: Estomba
country: Argentina
facility: Clínica Adventista Belgrano
state: Buenos Aires
city: La Plata
country: Argentina
facility: Framingham Centro Médico
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto CER S.A
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes SRL
state: Buenos Aires
city: San Miguel De Tucumán
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucumán
city: San Miguel De Tucumán
country: Argentina
facility: Consultorio de Investigaciones Reumatologicas
state: Tucumán
city: Athens
country: Greece
facility: Athens General Hospital 'G Gennimatas
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Larisa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloníki
country: Greece
facility: Kianous Stavros
city: Secunderabad
country: India
facility: Krishna Institute of Medical Sciences
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: AES - AS - Panchshil Hospital - Ahmedabad
state: Gujarat
city: Sūrat
country: India
facility: AES - AS - Unity Trauma Center and ICU - Unity Hospital - Surat
state: Gujarat
city: Hubli
country: India
facility: AES - AS - Sushruta Multispeciality Hospital & Research Center Pvt Ltd - Hubli
state: Karnataka
city: Nagpur
country: India
facility: Jasleen Hospital
state: Maharashtra
city: Mexicali
country: Mexico
facility: Centro de Investigación en Artritis y Osteoporosis
state: Baja California
city: San Miguel
country: Mexico
facility: Centro de Investigación y Tratamiento Reumatológico S.C
state: Distrito Federal
city: León
country: Mexico
facility: Morales Vargas Centro de Investigacion SC
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Bioclinica - Centro Integral En Reumatologia Sociedad Anónima de Capital Variable
state: Jalisco
city: Zapopan
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
state: Jalisco
city: Merida
country: Mexico
facility: Centro Peninsular de Investigacion S.C.P
state: Yucatán
city: Ciudad de Mexico
country: Mexico
facility: Consultorio de Reumatologia
city: Distrito Federal
country: Mexico
facility: AMAF Clinical Research,S.C.
city: Guadalajara
country: Mexico
facility: Clinica de Investigacion en Reumatologia y Obesidad
city: Jalisco
country: Mexico
facility: Centro de Estudios de Investigacion Basica Y Clinica SC
city: Łódź
country: Poland
facility: Centrym Medyczne AMED oddzial w Lodzi
state: Lodzkie
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol
state: Lubuskie
city: Krakow
country: Poland
facility: Pratia MCM
state: Malopolskie
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
state: Malopolskie
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK-MED
state: Mazowieckie
city: Warszawa
country: Poland
facility: Medycyna Kliniczna Marzena Waszczak-Jeka
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
state: Mazowieckie
city: Czestochowa
country: Poland
facility: Centrum Medyczne Czestochowa - PRATIA
state: Slaskie
city: Poznań
country: Poland
facility: Klinika Reumatologii i Rehabilitacji Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im W. Degi
state: Wielkopolskie
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
city: Kemerovo
country: Russian Federation
facility: Belyayev Clinical Hospital of the Kuzbass
city: Moscow
country: Russian Federation
facility: O.M. Filatov City Clinical Hospital #15
city: Smolensk
country: Russian Federation
facility: Departmental Hospital at Smolensk Station "rzhd" JSC
city: Belgrade
country: Serbia
facility: Institute of Rheumatology Belgrade
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Sevilla
country: Spain
facility: Hospital Quironsalud Infanta Luisa
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Veterans General Hospital
state: Province Of China
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Province Of China
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
state: Province Of China
city: Zaporizhzhia
country: Ukraine
facility: Medical Center of LLC Modern Clinic
state: Zaporiz'ka Oblast
city: Kyïv
country: Ukraine
facility: Limited Liability Company Medical Center Consilium
city: Poltava
country: Ukraine
facility: ME Poltava Reg.Clin.Hospital n.a.M.V.Skliphosovskyi of Poltava Reg.Council
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
affiliation: Horizon Therapeutics
name: Nisha Jain, MD
role: STUDY_DIRECTOR
References: