Trial Outcomes & Findings for PRV-3279-2a Trial in Systemic Lupus (NCT NCT05087628)

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.

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.

PRV-3279-2a Trial in Systemic Lupus

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.

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.

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.

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.

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.

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.

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 samples were collected at specified timepoints to evaluate serum concentration of 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.