Safety of the Herpes Zoster Subunit Vaccine in Lupus

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, placebo-controlled, non-inferiority crossover study will evaluate the Herpes Zoster Sunbit (HZ/su) vaccine in SLE patients in order to evaluate safety and immunogenicity in patients with variable baseline clinical activities, ages and immunosuppressant exposures. The investigators hypothesize that HZ/su administration will be non-inferior to placebo with respect to the risk of moderate or severe SLE flare(s) occurring within 24 weeks of receiving the first dose of the assigned treatment. In addition, the investigators hypothesize that immunogenicity of the vaccine in SLE patients will be at least 50% of levels observed in healthy subjects from prior large clinical trials.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Non-inferiority Crossover Study Evaluating the Safety and Immunogenicity of the Herpes Zoster Subunit Vaccine in Patients With Systemic Lupus Erythematosus

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

Intervention / Treatment
-----------------
* Biological: Herpes Zoster Subunit (HZ/su) Vaccine
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female or male ≥18 years of age at the time of signing the informed consent Meet the 2019 EULAR/ACR Classification Criteria for SLE Female subjects must use 1 effective method of avoiding pregnancy, from the time they sign consent until end of the study period unless the subject is surgically sterile (e.g., bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least 1 year postmenopausal, or practices sustained abstinence consistent with the subject's customary lifestyle. Postmenopausal is defined as at least 1 year since last menses and the subject has an elevated follicle-stimulating hormone (FSH) level greater than the threshold laboratory value of post-menopausal women at screening. Exclusion Criteria: Prior administration of the Herpes Zoster subunit vaccine (Shingrix) or the Varicella-Zoster virus vaccine live (Zostavax) Clinical HZ infection within 12 months prior to screening or during screening Hybrid SLEDAI >12 at screening visit Presence of a mild, moderate, or severe flare per the rSFI at time of screenin Increase in clinical SLEDAI parameters at time of enrollment relative to screening visit Any vaccine, including the final/booster dose of any SARS-CoV-2 vaccine, within six weeks enrollment Receipt of rituximab or cyclophosphamide within nine months of enrollment Participation in an interventional clinical trial of SLE or other therapeutics within six months of enrollment Moderate to severe infectious febrile illness or use of systemic antibiotics (antibacterial, antiviral, antifungal, or antiparasitic agent) within 4 weeks of enrollment Are pregnant, nursing, or planning a pregnancy while enrolled in the study Known primary or secondary immunodeficiency (malignancy, HIV, common variable immune deficiency) or medications used during cancer chemotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZ/su Vaccine, then Placebo<br>During the initial 24-week period (Period 1), participants will receive HZ/su injection at week 0 and week 8. During the second 24-week period (Period 2), participants will receive placebo saline injection at week 24 and week 32. | Biological: Herpes Zoster Subunit (HZ/su) Vaccine<br>* Manufactured by GSK Biologicals SA. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.<br>* Other names: SHINGRIX;Biological: Placebo<br>* Saline injection. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.<br>|
| Experimental: Placebo, then HZ/su Vaccine<br>During the initial 24-week period (Period 1), participants will receive placebo saline injection at week 0 and week 8. During the second 24-week period (Period 2), participants will receive HZ/su injection at week 24 and week 32. | Biological: Herpes Zoster Subunit (HZ/su) Vaccine<br>* Manufactured by GSK Biologicals SA. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.<br>* Other names: SHINGRIX;Biological: Placebo<br>* Saline injection. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of either Moderate or Severe Lupus Flares within 24 Weeks of First Dosing with HZ/su Vaccine | Classification of moderate or severe lupus flares based on revised Safety of Estrogens in Lupus Erythematosus, National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index [rSFI]. | Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of either Moderate or Severe Lupus Flares at Week 8 | Classification of moderate or severe lupus flares based on rSFI. | Week 8 | 
| Occurrence of either Moderate or Severe Lupus Flares at Week 24 | Classification of moderate or severe lupus flares based on rSFI. | Week 24 | 
| Occurrence of Mild, Moderate, or Severe Lupus Flares within 24 Weeks of First Dosing with HZ/su Vaccine | Classification of mild, moderate, or severe lupus flares based on rSFI. | Up to Week 48 | 
| Occurrence of New or Worsening Disease Activity in Any Organ System as Identified by BILAG 2004 within 24 Weeks of First Dosing with HZ/su Vaccine | The British Isles Lupus Assessment Group (BILAG) 2004 scores disease involvement within nine organ systems. Each of the 101 items are rated as 0 (not present), 1 (improving), 2 (same), 3 (worse), or 4 (new) in the last 4 weeks, compared with the previous 4 weeks. | Up to Week 48 | 
| Occurrence of Increase in PGA Score by More than 0.3 Points within 24 Weeks of First Dosing with HZ/su Vaccine | Physician's Global Assessment (PGA) is a 10-cm visual analogue scale (VAS) anchored at 0 (none) and 3 (severe) with intermediate lines at 1 (mild) and 2 (moderate). Higher scores indicate greater severity of disease activity. | Up to Week 48 | 
| Occurrence of Grade 3 or Higher Adverse Events as Per CTCAE or Solicited AIT within 24 Weeks of First Dosing with HZ/su Vaccine | Common terminology criteria for adverse events (CTCAE) and solicited assessments of intensity and toxicity (AIT) used to grade severity of adverse events. | Up to Week 48 | 
| Levels of Serum Varicella-Zoster Virus Anti-Glycoprotein E Antibodies at 4 Weeks after Last Dose of HZ/su Vaccine | Antibody levels measured using patient blood samples. | 4 Weeks after Last Dose of HZ/su Vaccine (Week 12 for Vaccine, then Placebo Arm; Week 36 for Placebo, then Vaccine Arm) | 
| Levels of Serum Varicella-Zoster Virus Anti-Glycoprotein E Antibodies at 24 Weeks after First Dose of HZ/su Vaccine | Antibody levels measured using patient blood samples. | 24 Weeks after First Dose of HZ/su vaccine (Week 24 for Vaccine, then Placebo Arm; Week 48 for Placebo, then Vaccine Arm) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Herpes Zoster Subunit Vaccine