RNA Vaccine for Shingles

Recruiting at 43 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Must not be taking: Immunosuppressants, Corticosteroids, RNA vaccines

Disqualifiers: Shingles, Heart disease, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: Unknown

900 Participants Needed

Trial Summary

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 immunosuppressive therapy or have received blood products recently, you may not be eligible to participate.

What data supports the effectiveness of the treatment Shingrix for shingles?

Shingrix is shown to be highly effective in preventing shingles and its complications, like postherpetic neuralgia, in adults aged 50 and older. Studies found that it significantly reduces the risk of shingles and maintains its protective effect over several years, with only mild to moderate side effects. ^{1 2 3 4 5}

Is the RNA vaccine for shingles safe for humans?

The RNA vaccine for shingles, known as Shingrix, has been shown to be generally safe in humans. Most people experience mild to moderate reactions like pain at the injection site, muscle aches, and fatigue, which are temporary. Serious side effects are rare and occur at similar rates as with a placebo. ^{1 2 4 5 6}

How is the RNA vaccine for shingles different from other treatments?

The RNA vaccine for shingles, using VZV modRNA, is unique because it uses a new platform of lipid nanoparticle-formulated mRNA to encode the VZV gE antigen, potentially eliciting a robust immune response similar to the existing Shingrix vaccine but without using live virus, making it suitable for immunocompromised individuals. ^{1 2 3 5 7}

What is the purpose of this trial?

This trial is testing a new shingles vaccine called VZV modRNA in healthy people aged 50-69. The vaccine uses mRNA to help the body recognize and fight the virus that causes shingles. The study aims to see how safe the vaccine is and how well it works.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

Healthy adults aged 50-69 can join this vaccine trial against shingles. They must be able to follow the study plan and not have heart disease, bleeding issues, or a history of severe vaccine reactions. Pregnant women, those on immunosuppressants, or with recent other vaccines are excluded.

Inclusion Criteria

I have a history of heart disease.

Participation in other interventional studies within 28 days prior to study entry or anticipated involvement through and including 6 months after the last dose of study intervention is prohibited. Participation in observational studies is permitted.

I do not have a bleeding disorder that makes injections unsafe for me.

Exclusion Criteria

I have a history of heart disease.

Participation in other interventional studies within 28 days prior to study entry or anticipated involvement through and including 6 months after the last dose of study intervention. Participation in observational studies is permitted.

You cannot engage in intense exercise 7 days before or after each study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Substudy A)

Participants receive 1 of 3 VZV modRNA vaccine candidates or the approved shingles vaccine. Vaccination is given as a 2-dose series or a single dose with saline.

8-12 months

Multiple visits for vaccinations and assessments

Treatment (Substudy B)

Participants receive either VZV modRNA vaccine at selected dose level/schedule/formulation or approved shingles vaccine.

Up to 5 years

Multiple visits for vaccinations and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including persistence-of-immunity assessments.

Up to 5 years

Treatment Details

Interventions

• Shingrix
• VZV modRNA

Trial Overview The trial is testing different candidates of a modified RNA shingles vaccine compared to an approved one (Shingrix). It's in two parts: Phase 1 tests safety and immune response with various doses/formulations; Phase 2 uses findings from Phase 1 for further evaluation over up to five years.

Participant Groups

Group I: Substudy B (SSB): Group 1 Experimental Treatment 1 Intervention

Candidate 2, Dose level 3, lyophilized, 0, 2 months schedule

Group II: SubStudy A (SSA): Group 1 Experimental Treatment 1 Intervention

Candidate 1, Dose Level 1, lyophilized, 0, 2 months schedule

Group III: SSB: Group 3 Experimental Treatment 1 Intervention

Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule (saline at month 2)

Group IV: SSB: Group 2 Experimental Treatment 1 Intervention

Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule

Group V: SSA: Group 7 Experimental Treatment 1 Intervention

Candidate 3, Frozen, 0, 2 months schedule

Group VI: SSA: Group 6 Experimental Treatment 1 Intervention

Candidate 2, frozen, 0, 2 months schedule

Group VII: SSA: Group 5 Experimental Treatment 1 Intervention

Candidate 1, Dose Level 2, Frozen, 0, 6 months schedule

Group VIII: SSA: Group 4 Experimental Treatment 1 Intervention

Candidate 1, Dose Level 2, frozen, 0, 2 months schedule

Group IX: SSA: Group 3 Experimental Treatment 1 Intervention

Candidate 1, Dose Level 3, lyophilized, 0, 2 months schedule

Group X: SSA: Group 2 Experimental Treatment 1 Intervention

Candidate 1, Dose Level 2, lyophilized, 0, 2 months schedule

Group XI: SSA: Group 10 Experimental Treatment 1 Intervention

Candidate 1, Dose level 4, lyophilized, 0, 6 months schedule (saline at month 6)

Group XII: SSB: Group 4 Active Control 1 Intervention

Shingrix, 0, 2 months schedule

Group XIII: SSA: Group 8 Active Control 1 Intervention

Shingrix, 0, 2 months schedule

Group XIV: SSA: Group 9 Active Control 1 Intervention

Shingrix, 0, 6 months schedule

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?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

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]

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]

A new mRNA vaccine platform (VZV gE mRNA/LNP) shows promise in eliciting a strong immune response against shingles, comparable to established vaccines like Shingrix™, while outperforming the live attenuated vaccine ZOSTAVAX® in terms of immune response magnitude.

The study utilized non-human primates to demonstrate that the immune responses generated by the mRNA vaccine and protein/adjuvant vaccine were similar to those observed in human clinical trials, supporting the use of NHP as a reliable model for future vaccine evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates. Monslow, MA., Elbashir, S., Sullivan, NL., et al.[2021]

HZ/Su, also known as 'Shingrix', is a new subunit vaccine designed to prevent shingles, particularly important for aging populations who are at higher risk.

Unlike the older live attenuated shingles vaccine, HZ/Su is suitable for a broader range of individuals, addressing safety concerns and potential long-term effectiveness issues associated with the previous vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus. Bharucha, T., Ming, D., Breuer, J.[2021]

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]

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 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]

References

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

Shingrix: A New Herpes Zoster Vaccine. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

[Zoster disease after Shingrix vaccination]. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates. [2021]

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

A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus. [2021]

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

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

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

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

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

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