New Rabies Vaccine for Rabies

No longer recruiting at 3 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Antimalarials, Antituberculosis, others

Disqualifiers: Rabies history, Immunodeficiency, Autoimmune, others

Compensation: Varies

Number of Visits: 2

Duration: 2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new experimental rabies vaccine, RG-SAM [CNE] vaccine, in healthy adults. Researchers aim to observe how the body responds to different doses of this vaccine technology, which uses a specific protein from the rabies virus. Participants will receive injections in the arm on a set schedule, and some will receive a placebo (a harmless substance used for comparison). Those who are generally healthy with no history of rabies exposure or autoimmune diseases might be suitable for this study.

As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding how it works in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use investigational products, certain vaccines, immunosuppressants, or antimalarial drugs close to the vaccination period.

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

Research has shown that the RG-SAM (CNE) vaccine appears safe in early studies. Animal tests demonstrated that the vaccine is well-tolerated, with no major side effects even after repeated doses. Another study found no concerning interactions between the vaccine and viruses in mice.

However, the RG-SAM (CNE) vaccine is a new technology and is just beginning human testing. While early results are promising, more information is needed to fully understand its safety in people. As this is a Phase 1 trial, the main focus is on safety and side effects, and any risks are still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RG-SAM [CNE] rabies vaccine due to its potentially innovative approach to immunization. Unlike traditional rabies vaccines, which typically involve inactivated virus particles, RG-SAM [CNE] utilizes a novel self-amplifying mRNA technology. This method could offer a more robust immune response with potentially fewer doses or lower quantities, making it an efficient alternative. Additionally, the ability to fine-tune dosing, as explored in the trial's different arms, might optimize safety and effectiveness, providing a flexible vaccination strategy tailored to individual needs.

What evidence suggests that this trial's treatments could be effective for rabies?

Research shows that the RG-SAM [CNE] vaccine, tested in this trial, has shown promise in animal studies. It triggered the expected immune response, specifically producing IgG antibodies, which are important for fighting infections. Previous studies have demonstrated that even low doses of this type of vaccine can lead to a strong immune response. In early studies, animals tolerated the vaccine well without serious side effects. This trial will evaluate different doses of the RG-SAM [CNE] vaccine—low, lower, medium, and lowest—to determine its effectiveness in preventing rabies in humans. ^{1 2 4 5 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Are You a Good Fit for This Trial?

Inclusion Criteria

Written informed consent obtained from the participant prior to performance of any study specific procedure.

Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. participation in genetics research, completion of the electronic diary cards, return for follow-up visits).

Healthy participants as established by medical history and clinical examination before entering into 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 experimental rabies vaccine intramuscularly on a 0, 2-month schedule

2 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person and virtual) for safety and immunogenicity assessments

Long-term follow-up

Evaluation of persistence of immunogenicity and monitoring for adverse events

18 months

What Are the Treatments Tested in This Trial?

Interventions

• RG-SAM [CNE] vaccine

How Is the Trial Designed?

Group I: Medium dose (Md-) RG SAM (CNE) group Experimental Treatment 1 Intervention

Healthy adults,18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) medium dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Day 1.

Group II: Lowest dose (Ltd-) RG SAM (CNE) group Experimental Treatment 1 Intervention

Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lowest dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Group III: Lower dose (Lrd-) RG SAM (CNE) group Experimental Treatment 1 Intervention

Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lower dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Group IV: Low dose (Ld-) RG SAM (CNE) group Experimental Treatment 1 Intervention

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Group V: RabAvert group Active Control 1 Intervention

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm and one intramuscular injection of saline solution in the other arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).

Group VI: Saline Placebo group Placebo Group 1 Intervention

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive two intramuscular injections of saline placebo, one in each arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age will receive one intramuscular injections of saline placebo in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04062669

NCT04062669 | A Study to Evaluate the Safety and ... Subjects in the low dose (Ld-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) low dose formulation, administered intramuscularlyat Days 1 and 61.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11290775/

Development of mRNA rabies vaccines - PMC - PubMed Central Overall, the animals showed good tolerance to the RG SAM (CNE) vaccine, which triggered the expected IgG immune response.

3. nature.com nature.com/articles/s41434-020-00204-y

Self-amplifying RNA vaccines for infectious diseases An effective immune response was also achieved using a relatively low-dose (50 µg per primer injection) of the saRNA in the CNE formulation, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10383046/

Advances in saRNA Vaccine Research against Emerging ... Data in phase I study demonstrated that the vaccine was well tolerated with no serious adverse events (AEs) related to vaccination.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S027323002030074X

Nonclinical safety assessment of repeated administration ... These results showed that the rabies SAM vaccine was well-tolerated by the animals and supported the clinical development program.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11405153/

Safety concern of recombination between self-amplifying ... The safety concern of recombination between SAM vaccines and viruses is mitigated in vivo, with no viable chimeras detected in mice.