CMV Vaccine for Cytomegalovirus

No longer recruiting at 1 trial location

Overseen By EU GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Viral hepatitis, Autoimmune disease, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: 549

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine for cytomegalovirus (CMV), a virus that can cause health problems, especially in people with weakened immune systems. The study aims to assess the safety of the Pentamer/gB/Adjuvant Vaccine, observe participant reactions, and evaluate its effectiveness in boosting the immune system against CMV. Participants will receive different doses to find the best balance between effectiveness and safety. Healthy adults without a history of severe allergies or autoimmune diseases who can follow safety guidelines may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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 immunosuppressants or immune-modifying drugs, you may need to stop them 3 months before the vaccine dose. Inhaled and topical steroids are allowed.

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

Research has shown that similar vaccines for cytomegalovirus (CMV) have been tested before and found safe in adults. In one study, a vaccine with gB antigens was well-tolerated even at low doses. Another study found that a different CMV vaccine was safe and successfully triggered immune responses in participants. These findings suggest that the vaccine in this trial could also be safe for humans.

As this is a Phase 1 trial, the main focus is on safety and determining the appropriate dose. Researchers start with lower doses and gradually increase them while monitoring for side effects. This careful approach helps ensure the treatment is safe for all participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for cytomegalovirus (CMV) focus on antiviral therapies, like ganciclovir or valganciclovir, which target the virus after infection. However, the pentamer/gB/adjuvant vaccine works differently by aiming to prevent CMV infections in the first place. Researchers are excited about this vaccine because it combines two specific antigens, pentamer and gB, with an adjuvant to boost the immune response. This approach could lead to stronger and longer-lasting immunity against CMV, offering a proactive defense rather than reactive treatment.

What evidence suggests that this trial's vaccine could be effective for cytomegalovirus?

Research has shown that a CMV vaccine using the gB protein with an adjuvant (a substance that boosts the immune system) is about 50% effective in preventing human cytomegalovirus (HCMV) infections. Another study found that the vaccine activates both antibody-related and cell-based immune responses, both crucial for fighting infections. These findings suggest that the vaccine can help the body build defenses against CMV. Early human tests demonstrated its safety, which is encouraging for future development. While the vaccine isn't perfectly effective yet, these early results are promising steps toward a working CMV vaccine. Participants in this trial will receive different combinations of the pentamer and gB antigens at varying doses, or a placebo, to further evaluate the vaccine's effectiveness and safety. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Healthy adults aged 18-50, able to follow the study plan. Women must use contraception and have a negative pregnancy test before receiving the vaccine. Participants should not be at high risk for CMV transmission or planning to move away during the trial. They can't join if they're using certain drugs, are pregnant or breastfeeding, or have received another CMV vaccine.

Inclusion Criteria

I am a healthy adult aged 18-50, can follow study rules, and meet all COVID-19 and reproductive health criteria.

For participants in EPOCH 2: Participants who completed Epoch 1, can comply with the protocol, have written informed consent, and can be rescheduled if they have active infections

Exclusion Criteria

For participants in EPOCH 1: Various medical conditions, prior/concomitant therapy restrictions, prior/concurrent clinical study experience, and other exclusions like pregnancy, high CMV exposure risk, and substance abuse

For participants in EPOCH 2: Immunodeficient conditions, specific medical histories, therapy restrictions, and concurrent clinical study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the candidate CMVsu vaccine at 0, 2, and 6 months in a step-wise dose escalation manner

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment until the end of the study

12 months

Multiple visits (in-person and virtual) until Day 546

What Are the Treatments Tested in This Trial?

Interventions

• Pentamer/gB/Adjuvant Vaccine

Trial Overview The trial is testing different doses of a new Cytomegalovirus (CMV) vaccine in healthy adults. It will look at safety and immune response by gradually increasing doses based on previous participants' reactions.

How Is the Trial Designed?

Group I: Pentamer(low)/gB(low)/Adjuvant Group Experimental Treatment 1 Intervention

Participants receive the candidate CMVsu vaccine consisting of a combination of low dose pentamer and low dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).

Group II: Pentamer (med)/gB(med)/Adjuvant Group Experimental Treatment 1 Intervention

Participants receive the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and medium dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).

Group III: Pentamer (med)/gB(low)/Adjuvant Group Experimental Treatment 1 Intervention

Participants receive the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and low dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).

Group IV: Pentamer (high)/gB(med)/Adjuvant Group Experimental Treatment 1 Intervention

Participants receive the candidate CMVsu vaccine consisting of a combination of high dose pentamer and medium dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).

Group V: Placebo Group Placebo Group 1 Intervention

Participants receive placebo (saline) at 0,2 and 6 months and are followed up until end of study (Day 546).

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead 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

Published Research Related to This Trial

The V160 CMV vaccine was found to be generally well-tolerated in both CMV-seronegative and seropositive adults, with no serious adverse events reported and only mild-to-moderate injection-site and systemic reactions observed.

The vaccine successfully elicited robust neutralizing antibody responses and T-cell activation, maintaining these levels for up to 12 months, indicating strong immunogenicity similar to that seen after natural CMV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. Adler, SP., Lewis, N., Conlon, A., et al.[2020]

The CMV vaccine using the envelope glycoprotein gB combined with the MF59 adjuvant was found to be more immunogenic than the same vaccine with alum, indicating a stronger immune response.

The trial, which involved a phase I study design with no serious adverse events reported, showed that the vaccine was safe, with only mild local and systemic reactions, suggesting it could be a promising candidate for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. Pass, RF., Duliegè, AM., Boppana, S., et al.[2008]

Cytomegalovirus (CMV) poses significant health risks to infants and immunocompromised patients, highlighting the need for effective vaccines to prevent CMV-related diseases.

Current research is advancing the development of CMV vaccines, but understanding the specific immune responses needed for effective protection remains crucial before these vaccines can be widely implemented in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in cytomegalovirus vaccine development. Schleiss, M.[2006]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38324766/

Human Cytomegalovirus mRNA-1647 Vaccine ... - PubMed Background: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) ...

2. academic.oup.com academic.oup.com/jid/article/230/3/e668/7628193

Results From a Phase 1 Randomized Clinical Trial | The ... This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses.

3. jci.org jci.org/articles/view/182317

A vaccine against cytomegalovirus: how close are we? The efficacy against primary HCMV infection in the phase II trial (NCT03486834) was 42% (168). Although the reported efficacy was suboptimal, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X23014524

An enveloped virus-like particle alum-adjuvanted ... The highest titers were seen in recipients of the alum adjuvanted 2.0 µg CMV gB-G vaccine; 100 % of these participants had responded after two ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05089630

NCT05089630 | A Study of Safety and Immune Response ... The purpose of this study is to assess the safety, reactogenicity and immune response of the candidate CMV recombinant protein subunit (CMVsu) vaccine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11420795/

Results From a Phase 1 Randomized Clinical Trial - PMC This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5716458/

Cytomegalovirus vaccine: phase II clinical trial results - PMC The gB/MF59 vaccine was clearly more effective than placebo in protecting from CMV infection. CMV infection was diagnosed in 31/216 (14%) placebo and 18/225 (8 ...