Safety of the Herpes Zoster Subunit Vaccine in Lupus

• ClinicalTrials.gov Identifier: NCT05559671
• Recruitment Status: Recruiting
• First Posted: September 29, 2022
• Last Update Posted: February 20, 2024
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Biological: Herpes Zoster Subunit (HZ/su) Vaccine; Biological: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 21, 2023
• Estimated Primary Completion Date: January 2027
• Estimated Study Completion Date: January 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: HZ/su Vaccine, then Placebo; 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; 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.; Other Name: SHINGRIX; Biological: Placebo; Saline injection. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.
Experimental: Placebo, then HZ/su Vaccine; 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; 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.; Other Name: SHINGRIX; Biological: Placebo; Saline injection. Administered as two-time injection of 0.5 mL each at either weeks 0 and 8 or weeks 24 and 32.

Outcome Measures

Primary Outcome Measures :

1. Occurrence of either Moderate or Severe Lupus Flares within 24 Weeks of First Dosing with HZ/su Vaccine [ Time Frame: Up to Week 48 ]
   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].

Secondary Outcome Measures :

1. Occurrence of either Moderate or Severe Lupus Flares at Week 8 [ Time Frame: Week 8 ]
   Classification of moderate or severe lupus flares based on rSFI.
2. Occurrence of either Moderate or Severe Lupus Flares at Week 24 [ Time Frame: Week 24 ]
   Classification of moderate or severe lupus flares based on rSFI.
3. Occurrence of Mild, Moderate, or Severe Lupus Flares within 24 Weeks of First Dosing with HZ/su Vaccine [ Time Frame: Up to Week 48 ]
   Classification of mild, moderate, or severe lupus flares based on rSFI.
4. 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 [ Time Frame: Up to Week 48 ]
   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.
5. Occurrence of Increase in PGA Score by More than 0.3 Points within 24 Weeks of First Dosing with HZ/su Vaccine [ Time Frame: Up to Week 48 ]
   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.
6. Occurrence of Grade 3 or Higher Adverse Events as Per CTCAE or Solicited AIT within 24 Weeks of First Dosing with HZ/su Vaccine [ Time Frame: Up to Week 48 ]
   Common terminology criteria for adverse events (CTCAE) and solicited assessments of intensity and toxicity (AIT) used to grade severity of adverse events.
7. Levels of Serum Varicella-Zoster Virus Anti-Glycoprotein E Antibodies at 4 Weeks after Last Dose of HZ/su Vaccine [ Time Frame: 4 Weeks after Last Dose of HZ/su Vaccine (Week 12 for Vaccine, then Placebo Arm; Week 36 for Placebo, then Vaccine Arm) ]
   Antibody levels measured using patient blood samples.
8. Levels of Serum Varicella-Zoster Virus Anti-Glycoprotein E Antibodies at 24 Weeks after First Dose of HZ/su Vaccine [ Time Frame: 24 Weeks after First Dose of HZ/su vaccine (Week 24 for Vaccine, then Placebo Arm; Week 48 for Placebo, then Vaccine Arm) ]
   Antibody levels measured using patient blood samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female or male ≥18 years of age at the time of signing the informed consent
3. Meet the 2019 EULAR/ACR Classification Criteria for SLE
4. 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:

1. Prior administration of the Herpes Zoster subunit vaccine (Shingrix) or the Varicella-Zoster virus vaccine live (Zostavax)
2. Clinical HZ infection within 12 months prior to screening or during screening
3. Hybrid SLEDAI >12 at screening visit
4. Presence of a mild, moderate, or severe flare per the rSFI at time of screenin
5. Increase in clinical SLEDAI parameters at time of enrollment relative to screening visit
6. Any vaccine, including the final/booster dose of any SARS-CoV-2 vaccine, within six weeks enrollment
7. Receipt of rituximab or cyclophosphamide within nine months of enrollment
8. Participation in an interventional clinical trial of SLE or other therapeutics within six months of enrollment
9. Moderate to severe infectious febrile illness or use of systemic antibiotics (antibacterial, antiviral, antifungal, or antiparasitic agent) within 4 weeks of enrollment
10. Are pregnant, nursing, or planning a pregnancy while enrolled in the study
11. Known primary or secondary immunodeficiency (malignancy, HIV, common variable immune deficiency) or medications used during cancer chemotherapy

Contacts and Locations

Contacts

Contact: Thomas Chalothron; 646-501-7384; Thomas.Chalothron@nyulangone.org

Contact: Janine Sullivan; 646-501-7390; Janine.Sullivan@nyulangone.org

Locations

United States, New York

NYU Langone Health; Recruiting

New York, New York, United States, 10016

Principal Investigator: Amit Saxena, MD

United States, Oklahoma

Oklahoma Medical Research Foundation; Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contact: Cristina Arriens 405-271-7303 cristina-arriens@omrf.org

Sponsors and Collaborators

NYU Langone Health

Investigators

• Principal Investigator: Amit Saxena, MD; NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT05559671
• Other Study ID Numbers: 22-00922
• First Posted: September 29, 2022
• Last Update Posted: February 20, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Amit Saxena (Amit.Saxena@nyulangone.org). The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to Amit.Saxena@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NYU Langone Health:

Herpes Zoster Subunit Vaccine

Additional relevant MeSH terms:

Herpes Zoster; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections