Shingrix Vaccine for Bone Marrow Transplant Recipients

(Allo Trial)

Overseen By Tori Rutherford, RN BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Prednisone, others

Disqualifiers: Active GVHD, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

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: 6

Duration: 1 year

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is designed to determine if the adjuvanted recombinant glycoprotein E (gE) herpes zoster (HZ) vaccine (Shingrix) has acceptable immunogenicity and safety in people who have undergone allogeneic stem cell transplant (allo-SCT). Specifically, it will determine the effect of the interval after transplantation on the immune response and if an additional dose of vaccine is needed to improve the vaccine-induced responses.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on significant immunosuppressive therapy or have been taking prednisone at high doses recently, you may not be eligible to participate.

What data supports the effectiveness of the Shingrix vaccine treatment for bone marrow transplant recipients?

Research shows that the Shingrix vaccine is effective in preventing herpes zoster (shingles) in older adults and those with weakened immune systems, such as bone marrow transplant recipients. It has been approved for use in immunocompromised individuals, demonstrating moderate to high effectiveness in preventing shingles and its complications. ^{1 2 3 4 5}

Is the Shingrix vaccine safe for bone marrow transplant recipients?

The Shingrix vaccine has been studied for safety in various groups, including those with weakened immune systems. Most people experience mild reactions like pain at the injection site or fever, and serious side effects are rare. Safety monitoring has not shown unexpected problems. ^{1 3 4 6 7}

How is the Shingrix vaccine different from other treatments for herpes zoster in bone marrow transplant recipients?

Shingrix is unique because it is a recombinant subunit vaccine, meaning it does not contain live virus, making it safer for immunocompromised individuals like bone marrow transplant recipients. It is administered in two doses and includes an adjuvant to boost the immune response, which is particularly important for those with weakened immune systems. ^{1 2 3 4 8}

Research Team

Myron Levin, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults aged 18-79 who've had an allogeneic stem cell transplant. They must be 1 year post-transplant and have received two doses of Shingrix vaccine. Women must use contraception and not be pregnant or breastfeeding. Excluded are those with active graft disease, recent high-dose steroids, other immunosuppressants, or vaccines.

Inclusion Criteria

I received my second Shingrix dose between 18 and 30 months ago.

I am between 18 and 79 years old and have received an allogeneic stem cell transplant.

I am a woman able to have children and agree to follow the study's birth control requirements.

Exclusion Criteria

I have not had a live vaccine in the last 4 weeks or a killed vaccine in the last 2 weeks.

I am not on strong immune-weakening medicines, except for transplant care.

I currently have active Graft Versus Host Disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Shingrix vaccine and are monitored for immunogenicity and safety

1 year

Routine clinic visits every 6 months post-transplantation

Follow-up

Participants are monitored for the occurrence of herpes zoster and post-herpetic neuralgia

1 year

Follow-up visits as needed for herpes zoster evaluation

Treatment Details

Interventions

• Zoster Vaccine Recombinant

Trial Overview The study tests the safety and immune response to the Shingrix vaccine in bone marrow transplant recipients. It examines if timing after transplantation affects immunity and whether an extra dose enhances protection.

Participant Groups

Group I: ≥ 3 years post stem cell transplant Experimental Treatment 1 Intervention

At Visit 1 participants will be given information about the nature of HZ and its recognition and given a questionnaire for completion should they develop HZ during the study. They will also be asked to contact the study team if they develop HZ so that further evaluation of potential HZ is completed and the details of the event recorded. A swab of an active lesion or crust from a dried lesion will be obtained for VZV PCR. A participant who develops HZ will be asked to complete the questionnaire weekly for 4 weeks and then at 8 and 12 weeks. In addition, the subject will be asked about pain medications taken during the episode. Information on HZ incidence will be supplemented from the clinic medical records and the electronic medical records. Subjects will be followed for 1 year after enrollment for the occurrence of HZ and of post-herpetic neuralgia (PHN).

Group II: 2-<3 years post stem cell transplant Experimental Treatment 1 Intervention

At Visit 1 participants will be given information about the nature of HZ and its recognition and given a questionnaire for completion should they develop HZ during the study. They will also be asked to contact the study team if they develop HZ so that further evaluation of potential HZ is completed and the details of the event recorded. A swab of an active lesion or crust from a dried lesion will be obtained for VZV PCR. A participant who develops HZ will be asked to complete the questionnaire weekly for 4 weeks and then at 8 and 12 weeks. In addition, the subject will be asked about pain medications taken during the episode. Information on HZ incidence will be supplemented from the clinic medical records and the electronic medical records. Subjects will be followed for 1 year after enrollment for the occurrence of HZ and of post-herpetic neuralgia (PHN).

Group III: 1-<2 years post stem cell transplant Experimental Treatment 1 Intervention

At Visit 1 participants will be given information about the nature of HZ and its recognition and given a questionnaire for completion should they develop HZ during the study. They will also be asked to contact the study team if they develop HZ so that further evaluation of potential HZ is completed and the details of the event recorded. A swab of an active lesion or crust from a dried lesion will be obtained for VZV PCR. A participant who develops HZ will be asked to complete the questionnaire weekly for 4 weeks and then at 8 and 12 weeks. In addition, the subject will be asked about pain medications taken during the episode. Information on HZ incidence will be supplemented from the clinic medical records and the electronic medical records. Subjects will be followed for 1 year after enrollment for the occurrence of HZ and of post-herpetic neuralgia (PHN).

Zoster Vaccine Recombinant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Shingrix for:

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

Approved in European Union as Shingrix for:

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

Approved in Canada as Shingrix for:

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

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a phase 3 study involving 569 adults with haematological malignancies, the adjuvanted recombinant zoster vaccine (Shingrix) demonstrated a strong immunogenic response, with 80.4% of participants showing a humoral vaccine response compared to only 0.8% in the placebo group, indicating its efficacy in this high-risk population.

While the vaccine was more reactogenic than placebo, with higher reports of pain and fatigue, the overall safety profile was similar between the vaccine and placebo groups, suggesting that the benefits of vaccination outweigh the risks for immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Dagnew, AF., Ilhan, O., Lee, WS., et al.[2020]

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 Zoster Vaccine Recombinant, Adjuvanted (Shingrix) is effective in preventing herpes zoster in adults aged 50 and older, and its use has been expanded to include adults aged 18 and older who are immunocompromised, making it the first vaccine approved for this group.

With moderate to high efficacy and a good safety profile, Shingrix has the potential to significantly reduce the incidence of herpes zoster and its complications, as recommended by health authorities like the FDA and ACIP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. Anderson, TC., Masters, NB., Guo, A., et al.[2022]

A 65-year-old woman with multiple myeloma developed disseminated zoster and acute retinal necrosis after receiving the recombinant subunit vaccine (Shingrix), marking the first reported case of VZV infection following this vaccine.

While the recombinant subunit vaccine is generally considered safe and effective, this case highlights the need for clinicians to be aware of the rare possibility of VZV infection or reactivation in immunocompromised patients, despite the vaccine's approval and recommendations for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute retinal necrosis following recombinant subunit varicella-zoster virus vaccine. Chen, RI., Deaner, JD., Srivastava, SK., et al.[2022]

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]

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]

A review of 2.5 years of post-marketing data from over 32 million doses of the adjuvanted recombinant zoster vaccine (RZV) found no significant safety concerns related to vesicular and bullous skin eruptions following vaccination.

The analysis showed that the number of herpes zoster (HZ) cases reported was lower than expected in the general population, suggesting that RZV vaccination does not increase the risk of HZ reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Analysis of Spontaneously Reported Data of Vesicular and Bullous Cutaneous Eruptions Occurring Following Vaccination with the Adjuvanted Recombinant Zoster Vaccine. Pirrotta, P., Tavares-Da-Silva, F., Co, M., et al.[2022]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Shingrix: A New Herpes Zoster Vaccine. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Acute retinal necrosis following recombinant subunit varicella-zoster virus vaccine. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Zoster disease after Shingrix vaccination]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

An Analysis of Spontaneously Reported Data of Vesicular and Bullous Cutaneous Eruptions Occurring Following Vaccination with the Adjuvanted Recombinant Zoster Vaccine. [2022]

8. England 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. [2023]