Study of VIB7734 for the Treatment of Moderate to Severely Active SLE

Study Overview
=================
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.

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

Conditions
-----------------
Lupus Erythematosus, Systemic

Intervention / Treatment
-----------------
* Drug: VIB7734
* Other: Placebo


Participation Criteria
=================
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: SLEDAI-2K total score ≥ 6 at Screening, excluding fever, SLE headache, or organic brain syndrome. 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). 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 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): 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel-arm study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIB7734 SC (dosing interval 1)<br> | Drug: VIB7734<br>* VIB7734<br>* Other names: HZN-7734;|
| Experimental: VIB7734 SC (dosing interval 2)<br> | Drug: VIB7734<br>* VIB7734<br>* Other names: HZN-7734;|
| Placebo Comparator: Placebo SC (dosing interval 3)<br> | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants who achieve BICLA and OGC (oral glucocorticoid) reduction response at Week 48 | Participants will have BICLA (BILAG 2004 Index-Based Combined Lupus Assessment) and oral glucocorticoid assessment at week 48. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with CLASI-A score ≥ 10 at Baseline (Day 1) who achieve ≥ 50% reduction from Baseline (Day 1) in CLASI-A score at Week 12 | Cutaneous Lupus Erythematosus Disease Area and Severity Index will be measured at week 12. The scoring consists of 2 parts: inflammatory activity of the disease and damage done by the disease. | Week 12 | 
| Proportion of Participants achieving an SRI-4 response and an OGC dose ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at Week 48 | The SRI-4 (SLE Responder Index) is defined as meeting all criteria compared to baseline, (e.g. no worsening of symptoms). | Week 48 | 
| Proportion of Participants at OGC dose ≥ 10 mg prednisone or equivalent at Baseline (Day 1) who achieve an OCG of ≤ 7.5 mg/day prednisone or equivalent at Week 36 through Week 48 |  | Week 36 to Week 48 | 
| Proportion of Participants achieving LLDAS (Lupus Low Disease Activity State) at Week 48 | LLDAS is a composite measure of SLE disease activity that measures 5 criteria: SLEDAI-2K ≤ 4, with no activity in major organ systems, no new lupus disease activity, PGA ≤ 1 (scale 0 to 3), current prednisone (or equivalent) dose ≤ 7.5 mg daily, tolerated maintenance doses of immunosuppressive drugs and approved biological agents. | Week 48 |