PRV-3279-2a Trial in Systemic Lupus (PREVAIL-2)

Phase 2a, Randomized, Double-blind, Placebo-controlled Trial of PRV-3279 EVAluation In Lupus

The PREVAIL-2 study was designed to assess the safety and potential efficacy of PRV-3279 in flare prevention in systemic lupus erythematosus (SLE) participants with active disease after amelioration induced by corticosteroid treatment.

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Other: Placebo; Biological: PRV-3279

Detailed Description

This was a randomized, double-blind, placebo-controlled study in adult participants with active SLE. Approximately 100 eligible participants were randomized at a 1:1 ratio to receive treatment with either PRV-3279 or placebo.

Eligible participants included male or female adults, 18 to 70 years of age, with a diagnosis of SLE for at least 6 months.

The study drug was administered every 4 weeks for 20 weeks in a double-blind fashion, followed by an 8-week safety follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Investigational Site Number : 310
  • Beijing, China, 100730
    • Investigational Site Number : 301
  • Changchun, China, 130021
    • Investigational Site Number : 309
  • Guangzhou, China, 510080
    • Investigational Site Number : 302
  • Nanchang, China, 330006
    • Investigational Site Number : 303
  • Nanjing, China, 210008
    • Investigational Site Number : 307
  • Shanghai, China, 200127
    • Investigational Site Number : 306
  • Tianjin, China, 300052
    • Investigational Site Number : 305
  • Wuhan, China, 430030
    • Investigational Site Number : 304
• Hong Kong
  • Pok Fu Lam, Hong Kong, 999077
    • Investigational Site Number : 202
  • Tuenmen, Hong Kong, 999077
    • Investigational Site Number : 201
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Centro Reumatologico de Caguas- Site Number : 112
  • San Juan, Puerto Rico, 00917
    • Private Practice - Dr. Karina Vila Rivera- Site Number : 117
  • San Juan, Puerto Rico, 909
    • BCR Medical Center Inc.- Site Number : 129
• United States
  • California
    • Apple Valley, California, United States, 92307
      • Medvin Clinical Research - Apple Valley- Site Number : 133
    • Covina, California, United States, 91722
      • Medvin Clinical Research - Covina - West San Bernardino Road- Site Number : 106
    • La Jolla, California, United States, 92037
      • University of California San Diego - La Jolla- Site Number : 108
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles Medical Center- Site Number : 122
    • Los Angeles, California, United States, 91345
      • Facey Medical Group - Los Angeles- Site Number : 126
    • Rancho Mirage, California, United States, 92270
      • Desert Medical Advances- Site Number : 114
    • Tujunga, California, United States, 91042
      • Medvin Clinical Research - Tujunga- Site Number : 119
    • Whittier, California, United States, 90602
      • Medvin Clinical Research - Whittier- Site Number : 118
  • Florida
    • Avon Park, Florida, United States, 33825
      • Highlands Advanced Rheumatology & Arthritis Center- Site Number : 116
    • Fort Lauderdale, Florida, United States, 33309
      • Center for Rheumatology, Immunology and Arthritis- Site Number : 109
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research- Site Number : 111
    • Tamarac, Florida, United States, 33321
      • D&H Tamarac Research Center- Site Number : 123
    • Tampa, Florida, United States, 33613
      • Florida Hospital Tampa- Site Number : 107
  • Illinois
    • Vernon Hills, Illinois, United States, 60061
      • Vernon Hills Medical Associates- Site Number : 128
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center - Jefferson Highway- Site Number : 113
  • Michigan
    • Troy, Michigan, United States, 48084
      • Revival Research Corporation - Michigan - ClinEdge - PPDS- Site Number : 124
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center- Site Number : 110
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-2536
      • Yale University School of Medicine- Site Number : 125
  • Texas
    • Grapevine, Texas, United States, 76051
      • Grapevine Rheumatology Clinic- Site Number : 103
    • Houston, Texas, United States, 77084
      • Accurate Clinical Management - Greenhouse Road- Site Number : 104
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research - Houston Resource Parkway- Site Number : 105
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute- Site Number : 121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A diagnosis of SLE for at least 6 months prior to the Screening visit
2. Meet the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for SLE at Screening

3. Have moderate to severe disease activity despite stable standard-of-care medication defined as:

   At screening: hSLEDAI score ≥6 (≥4 points of which must come from non-serological finding), OR at least one BILAG A or one B score; At randomization: ≥4-point drop in hSLEDAI, OR one BILAG letter grade improvement in at least one A or B score present at Screening, and investigator or central adjudication committee (CAC) rating of definite improvement or major or complete improvement

4. Able and willing to stop all lupus treatments, except antimalarials, corticosteroids (prednisone equivalent ≤ 10 mg), and NSAIDs

Exclusion Criteria:

1. Active lupus nephritis or active central nervous system manifestations of SLE
2. Other inflammatory or autoimmune diseases that, in the opinion of the Investigator or CAC, may confound efficacy evaluations
3. Common variable immunodeficiency syndrome or any other clinically significant immunodeficiency
4. Known COVID-19 infection in the 4 weeks before Screening or positive SARS-CoV-2 RNA test
5. Received a live attenuated vaccine within 2 months of Screening, received a non-live or mRNA vaccine within 2 weeks of Screening, or expecting to receive any vaccine during the study period
6. Any recent infection requiring antibiotics within two weeks of Screening or any recent infection requiring IV antibiotics or hospitalization within 1 month of Screening
7. Any condition for which, in the opinion of the Investigator or CAC, participation in the study would not be in the best interest of the patient (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments
8. Participated in any interventional clinical trial within 42 days prior to Screening or within five half-lives of the investigational product, whichever is longer
9. Received rituximab or equivalent treatment that depletes B cells within 6 months of Screening unless return of B cells to pre-treatment value or normal range can be demonstrated.
10. Received tumor necrosis factor inhibitors, interleukin antagonists, or other biologics, including belimumab, within 42 days or five half-lives of the agent, whichever is longer.
11. Received IV immunoglobulin (IVIG) or IV cyclophosphamide within 2 months, prednisone ≥ 100 mg/day for more than 30 days within 2 months, or plasmapheresis within two months of the Screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRV-3279; Sterile solution for intravenous administration, every 4 weeks	Biological: PRV-3279; Bi-specific antibody-based molecule; Other Names: SAR446811
Experimental: Placebo; Sterile solution for intravenous administration, every 4 weeks	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained the Improvement in Systemic Lupus Erythematosus (SLE) Disease Activity From Baseline to Week 24	Improvement in SLE disease activity:no lupus flare during baseline to Week 24. Lupus flare:Investigator's assessment that SLE activity met Lupus Foundation of America international consensus definition for flare (defined as measurable increase in disease activity in 1 or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements,must be considered clinically significant by the assessor,and usually there would be at least consideration of a change or an increase in treatment);a score of "definite worsening" or "severe worsening" on Clinician's Global Impression of Change;and at least 1 of following occurrences: an increase of >=4 points from baseline in hybrid Safety of Estrogens in Lupus Erythematosus National Assessment- Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score (hSLEDAI),or >=1 organ with an A score (severe) or B score (moderate) item rated new or worse on British Isles Lupus Assessment Group (BILAG) Index.	Baseline (Day 1) to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Treatment Failure From Baseline to Week 24	Treatment failure was defined compared to baseline as the occurrence of an SLE flare (as defined in the primary outcome measure #1); or missing 2 consecutive doses or 3 or more total doses of the study treatment for any reason; or initiation of a new SLE medication; or increased dose of current SLE medication, with the exception of nonsteroidal anti-inflammatory drugs; or participant withdrawal from the study before the Week 24 visit. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Estimations were based on the Kaplan-Meier method.	Baseline (Day 1) to Week 24
Percentage of Participants Who Met European League Against Rheumatism (EULAR)-Recommended Goal of Low Disease Responders From Baseline Until Week 24	EULAR recommended goal of low disease responders were defined as participants who met either of following criteria: hSLEDAI score <3 (lower disease activity) or all BILAG scores were C (mild disease activity), or D (no disease activity in an organ previously affected) or E (organ inactive and never previously active). Baseline was defined as the last non-missing value prior to the first dose of study treatment. Percentages are rounded off to the tenth decimal place.	Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 24
Change From Screening Until Week 24 in the Physical Component Score (PCS) in the Short Form 36 (SF-36) Health Survey	SF-36 health survey consisted of 36 items which measured 8 subscales relevant to quality of life (QOL):physical functioning(PF),general health(GH),mental health(MH),vitality(VT),role physical(RP),role emotional(RE),bodily pain(BP), and social functioning(SF).Score range for each of 8 subscales was from 0(maximum disability) to 100(no disability);higher scores indicated good health condition. Responses on SF-36 were used to calculate 2 summary scores: PCS contributed by PF,RP,BP and GH and mental component summary(MCS) contributed by MH,RE, SF and VT. Summations of item scores of same domain gave sub-scale scores, which were transformed to calculate summary scores of PCS and MCS. Both PCS and MCS score ranges from 0(worst) to 100(best); higher scores indicated less disability and better QoL. Change from screening (post-screening value minus screening value) until Week 24 in PCS in SF-36 health survey is presented. Baseline:last non-missing value prior to first dose of study treatment.	Screening (Days -42 to -1), Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 24
Percentage of Participants Who Met the Criteria for Systemic Lupus Erythematosus Responder Index-4 (SRI-4) From Baseline Until Week 24	SRI-4 was defined as a hSLEDAI score decrease of >=4 points; and no new organs with a BILAG A (severe) score; and no more than 1 new organ with a BILAG B (moderate) score; and no SELENA-SLEDAI physician's global assessment (ssPGA) score increase of >0.3 points. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Percentages are rounded off to the tenth decimal place.	Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 24
Percentage of Participants Who Met the British Isles Lupus Assessment Group-Based Combined Lupus Assessment (BICLA) Criteria From Baseline Until Week 24	BICLA criteria was defined as reduction by >=1 grade in all organs with BILAG A (severe) or B (moderate) scores; and no worsening of SLEDAI or other BILAG organs; and no ssPGA score increase of >=0.3 points. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Percentages are rounded off to the tenth decimal place.	Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), TEAEs Leading to Treatment Discontinuation and Treatment-Emergent Adverse Events of Special Interest (TEAESIs)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or any other medically important event. A TEAE was defined as an AE that developed, worsened or became serious during the TE period. An AESI was defined as a TEAE including SAE, that were of scientific and medical concern specific to PRV-3279, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was considered appropriate.	From first dose of study treatment (Day 1) up to 56 days post last dose of study treatment, up to 29.1 weeks
Serum Concentrations of PRV-3279	Serum samples were collected at specified timepoints to evaluate serum concentration of PRV-3279.	Pre-dose and 2 hours post-dose on Days 1, 29, 57, 86, 113, 141, 169 and 197; 24, 48, 72, 168, 336 hours post-dose on Days 1 and 141
Number of Participants With Anti-Drug Antibodies (ADAs) Against PRV-3279	Blood samples were collected at specified timepoints to evaluate the presence of ADA against PRV-3279. Treatment-emergent ADA was defined as at least 1 treatment-induced or treatment-boosted ADA at any time after first study treatment administration. Treatment-induced ADA was defined as ADA that developed at any time after first study treatment administration and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented.	From first dose of study treatment (Day 1) up to 56 days post last dose of study treatment, up to 29.1 weeks

Collaborators and Investigators

• Sponsor: Provention Bio, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Actual): May 14, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: SLE; Systemic Lupus Erythematosus
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: PRV-3279-2a; ACT18113 (Other Identifier: Sanofi Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No