Shingrix Vaccine for Kidney Transplant Recipients

Overseen By Tori Rutherford, RN BSN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Investigational drugs

Disqualifiers: Herpes zoster, Immunodeficient conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 months

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the Shingrix vaccine to assess its safety and effectiveness in individuals who have had a kidney transplant. Participants on the kidney transplant waiting list will receive two doses of Shingrix, and if they undergo a transplant within 16 months, they may receive a third dose. The study aims to understand the immune response in these patients. Suitable candidates for this trial are those on a kidney transplant waiting list who have not had shingles or related vaccines in the past three years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take investigational drugs 30 days before or during the study, and you should avoid certain vaccines close to the time you receive Shingrix.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Shingrix vaccine is generally safe for individuals who have undergone organ transplants, such as kidney transplants. Studies indicate that Shingrix is well-tolerated in these patients, with most side effects being mild, like soreness at the injection site or a slight fever. Serious side effects are rare.

One study administered Shingrix to people with solid organ transplants, and the results demonstrated its safety and effectiveness in protecting against shingles, a painful rash caused by a virus. The vaccine was also tested in various groups, including those with weaker immune systems, and showed positive outcomes.

The FDA's approval of Shingrix for shingles in the general population supports its safety, indicating it has been tested in many people and found safe for use. Overall, Shingrix maintains a strong safety record, even for those with organ transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Shingrix vaccine for kidney transplant recipients because it offers enhanced protection against shingles, a concern for those with weakened immune systems. Unlike the standard shingles vaccines, Shingrix in this trial is adapted specifically for transplant patients. They receive a potential third booster dose post-transplantation, which might help maintain immunity in an immune-compromised state. This tailored approach could lead to improved outcomes and fewer complications from shingles in this vulnerable group.

What evidence suggests that the Shingrix vaccine might be an effective treatment for kidney transplant recipients?

Research has shown that the Shingrix vaccine effectively reduces the risk of shingles in organ transplant recipients, including those with kidney transplants. In this trial, kidney transplant recipients will receive the standard two doses of Shingrix before transplantation, with a possible third dose several months after transplantation if they meet specific criteria. Studies indicate that the vaccine works well both before and after kidney transplants by triggering a strong immune response. Specifically, Shingrix has maintained its ability to provoke an immune response in kidney transplant patients. Additionally, Shingrix effectively prevents shingles in the general population, significantly lowering the number of cases. Overall, evidence supports Shingrix's effectiveness in preventing shingles in kidney transplant recipients. ^{1 2 6 7 8}

Who Is on the Research Team?

Myron J Levin, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults on the kidney transplant waiting list, expected to receive a transplant within 3-16 months. Women must use contraception and have a negative pregnancy test before vaccination. Excluded are those with recent herpes vaccines, positive cPRA scores, other vaccine or drug conflicts, travel constraints, immune suppression not related to transplantation, multi-organ transplants or acute illness.

Inclusion Criteria

On the waiting list at the participating institutions for renal transplantation with anticipated transplantation to occur at > 3 months to 16 months after listing

Female subjects of non-childbearing potential (tubal ligation, hysterectomy, ovariectomy or post-menopausal)

Female subjects of childbearing potential who have practiced adequate contraception for 30 days prior to vaccination, have a negative pregnancy test on day of vaccination, and have agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccine series

Exclusion Criteria

Herpes zoster vaccine or varicella vaccine within 3 years of study entry

Any positive cPRA score prior to enrollment

No investigational drugs from 30 days before enrollment or planned during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the standard 2 doses of Shingrix, with a potential 3rd dose for those transplanted by 16 months

16 months

Multiple visits for each vaccine dose

Follow-up

Participants are monitored for safety, tolerability, and immune response, including SAEs, pIMDs, and occurrence of HZ

36 months

Regular contacts for safety and immunology assessments

What Are the Treatments Tested in This Trial?

Interventions

• Shingrix

Trial Overview The Shingrix vaccine's safety and effectiveness in prompting an immune response are being tested in kidney transplant recipients. Participants will get the standard two doses of Shingrix while on the waiting list; if they've been transplanted by 16 months post-listing, they may receive a third dose.

How Is the Trial Designed?

Group I: Transplanted subject Active Control 1 Intervention

In addition to receiving standard dose (2) of Shingrix prior to transplantation, participant may receive a 3rd dose several months after transplantation if they meet criteria related to no rejection.

Group II: Non-Transplanted subject Placebo Group 1 Intervention

Receives standard Shingrix dose (2), but not transplanted within 16 month time frame post-dose, so does not receive additional Shingrix dose.

Shingrix is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Shingrix for:

• Prevention of shingles in healthy adults over age 50 and in immunocompromised adults over age 18

Approved in European Union as Shingrix for:

• Prevention of herpes zoster (shingles) and postherpetic neuralgia (PHN) in adults 50 years of age and older

Approved in Canada as Shingrix for:

• Prevention of herpes zoster (shingles) in adults 50 years of age and older

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

The recombinant zoster vaccine (RZV; Shingrix) is effective and recommended for adults aged 50 and older, showing a safety profile consistent with prelicensure trials, where serious adverse events were similar to placebo rates.

In the first 8 months post-licensure, out of 3.2 million doses distributed, 4,381 adverse event reports were received, with common reactions being fever and injection site pain, but no unexpected safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018. Hesse, EM., Shimabukuro, TT., Su, JR., et al.[2020]

Shingrix® is a highly effective recombinant zoster vaccine that significantly reduces the risk of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged 50 and older, with efficacy remaining strong even after 4 years.

While Shingrix® is associated with more side effects than a placebo, such as injection-site reactions and fatigue, these reactions are generally mild to moderate and transient, making it a well-tolerated option for preventing HZ and PHN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. Syed, YY.[2022]

Shingrix is a new vaccine designed to prevent herpes zoster, commonly known as shingles, which can cause painful rashes and complications.

Clinical trials have shown that Shingrix is highly effective in reducing the incidence of shingles in adults, particularly in older populations, making it a significant advancement in herpes zoster prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shingrix: A New Herpes Zoster Vaccine. Maltz, F., Fidler, B.[2020]

The two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) has shown over 90% efficacy in preventing herpes zoster (HZ) and its complications in individuals aged 50 and older, sustained for at least 4 years.

RZV not only restores immunity against the varicella zoster virus but also demonstrates a cost-effective option for vaccination in the US population aged 50+, especially when compared to the older live-attenuated vaccine (Zostavax).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention. Lecrenier, N., Beukelaers, P., Colindres, R., et al.[2019]

This study aims to evaluate the immune response to the Shingrix vaccine in 308 patients, including those with liver cirrhosis and liver transplant recipients, to understand how immunosuppression affects vaccine efficacy.

By measuring specific antibody and T cell responses at multiple time points, the research seeks to establish a routine test for monitoring vaccination success and its correlation with clinical protection against shingles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiza-Titre increase and enhanced immunity through an adjuvanted, recombinant herpes zoster subunit vaccine in patients with liver cirrhosis and post-liver transplantation: a study protocol for a prospective cohort study. Vollmer-Raschdorf, S., Rashidi-Alavijeh, J., Voigt, S., et al.[2023]

Shingrix is an approved vaccine in Germany for preventing shingles (zoster) and its complications, specifically for adults aged 60 and older.

If patients experience bullous skin lesions after receiving Shingrix, it is important to consider the possibility of zoster disease and report any unexpected side effects to the appropriate medical authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Zoster disease after Shingrix vaccination]. Kohn, D., Wetzig, T.[2021]

SHINGRIX, a non-live herpes zoster vaccine, is safe for patients on immunosuppressive therapy, making it a suitable option for those with inflammatory bowel disease who are at higher risk for infections.

A case report of a 74-year-old woman with ulcerative proctosigmoiditis revealed blistering autoimmune skin disorders following SHINGRIX vaccination, suggesting a potential, though previously unreported, adverse effect of the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review. Bell, H., Kamal, N., Wong, U.[2021]

Vaccination with the Shingrix™ vaccine significantly increased VZV-specific cellular immunity in kidney transplant recipients, with an 8.0-fold increase in immune response one month after the second dose.

Factors such as male sex, good kidney function, and specific immunosuppressive treatments were associated with stronger immune responses, while diabetes mellitus was linked to weaker responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, Longitudinal Study on Specific Cellular Immune Responses after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Kidney Transplant Recipients. Lindemann, M., Baumann, C., Wilde, B., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10679076/

2706. Effectiveness and Safety of Shingrix Vaccination in ... Conclusion. The Shingrix vaccine, when administered to SOTR post-transplant, is safe and likely effective in reducing the rate of herpes zoster.

2. shingrixhcp.com shingrixhcp.com/home-ic/immunogenicity-data/post-renal-transplant/

Post-Renal Transplant | SHINGRIX (Zoster Vaccine ... Learn more about humoral and cellular immunogenicity in post-renal transplant patients. Explore the study design to learn more.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04128189

NCT04128189 | Shingrix in Renal Transplant Recipients This study evaluates the safety and immune response of the Shingrix vaccine in kidney transplant recipients. Participants on the waiting list for kidney ...

4. clinicalmicrobiologyandinfection.org clinicalmicrobiologyandinfection.org/article/S1198-743X(23)00084-8/fulltext

Clinical effectiveness of zoster vaccine live in kidney ... RZV showed high overall immunogenicity and efficacy in preventing HZ in the general population [6,7]. High immunogenicity of RZV in kidney ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7336348/

Recombinant zoster vaccine (Shingrix®): a new option for ... Vaccine efficacy for PHN decreased from 66.5% to 60.1%, and vaccine efficacy for HZ incidence reduction decreased from 51.3% to 39.6% during the same time ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03993717

NCT03993717 | Solid Organ Transplant SHINGRIX This study will help us assess the safety and efficacy of a new shingles vaccine, SHINGRIX in Kidney Transplant patients.

7. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-SHINGRIX.pdf

Package Insert - SHINGRIX The risk of developing HZ, which increases with age and with immunosuppression due to disease and/or therapy, appears to be related to a decline in varicella ...

8. astctjournal.org astctjournal.org/article/S1083-8791(19)31304-7/fulltext

Safety of the Recombinant Herpes-Zoster Subunit Vaccine ... The recombinant subunit vaccine containing VZV glycoprotein E with AS01 B adjuvant system (HZ/su, or Shingrix) has safety and efficacy data after autologous ...