Systemic Lupus Erythematosus
Conditions
Keywords
SLE, Systemic Lupus Erythematosus
Brief summary
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.
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.
Interventions
BIOLOGICALPRV-3279
Bi-specific antibody-based molecule
OTHERPlacebo
Placebo
Sponsors
Provention Bio, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained the Improvement in Systemic Lupus Erythematosus (SLE) Disease Activity From Baseline to Week 24 | Baseline (Day 1) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Treatment Failure From Baseline to Week 24 | Baseline (Day 1) 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. |
| Percentage of Participants Who Met European League Against Rheumatism (EULAR)-Recommended Goal of Low Disease Responders From Baseline Until Week 24 | Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 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. |
| Change From Screening Until Week 24 in the Physical Component Score (PCS) in the Short Form 36 (SF-36) Health Survey | Screening (Days -42 to -1), Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 24 | 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. |
| Percentage of Participants Who Met the Criteria for Systemic Lupus Erythematosus Responder Index-4 (SRI-4) From Baseline Until Week 24 | Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 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. |
| Percentage of Participants Who Met the British Isles Lupus Assessment Group-Based Combined Lupus Assessment (BICLA) Criteria From Baseline Until Week 24 | Baseline (Day 1) and Weeks 4, 8, 12, 16, 20 and 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. |
| 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) | From first dose of study treatment (Day 1) up to 56 days post last dose of study treatment, up to 29.1 weeks | 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. |
| Serum Concentrations 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 | Serum samples were collected at specified timepoints to evaluate serum concentration of PRV-3279. |
| Number of Participants With Anti-Drug Antibodies (ADAs) Against PRV-3279 | From first dose of study treatment (Day 1) up to 56 days post last dose of study treatment, up to 29.1 weeks | 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. |
Countries
China, Hong Kong, Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
The study was conducted at 36 centers in 3 countries. A total of 68 participants were screened from 20 January 2022 to 25 August 2023, of which 40 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria. The study was terminated early due to strategic reasons with no safety concerns.
Pre-assignment details
A total of 28 participants were randomized in a 1:1 ratio to receive either PRV-3279 10 milligram per kilogram (mg/kg) or placebo. Randomization was stratified by the presence or absence of serum anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies and the presence or absence of elevated B cell gene signature as defined by B cell pathway expression pathway testing.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 11.96 |
| Anti-dsDNA antibodies per Interactive Web Response System (IWRS) Absence | 20 Participants |
| Anti-dsDNA antibodies per Interactive Web Response System (IWRS) Presence | 3 Participants |
| B cell gene signature per IWRS High | 21 Participants |
| B cell gene signature per IWRS Low | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 6 / 13 | 7 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
None listed