VLP Peanut for Peanut Allergy

(PROTECT Trial)

Recruiting at 9 trial locations

Overseen By Pieter-Jan De Kam, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Allergy Therapeutics

Disqualifiers: Pregnancy, Severe asthma, Anaphylaxis, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This phase I clinical trial is designed to evaluate the safety and tolerability of VLP Peanut in healthy subjects and in subjects with peanut allergy (PA). This clinical trial will evaluate the immunotoxicity profile of VLP Peanut in healthy subjects and assess the immunotoxicity profile and the degree of reactogenicity (allergenicity) in subjects with PA. This clinical trial will also explore preliminary proof of efficacy of VLP Peanut in subjects with PA.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have participated in another clinical trial with investigational drugs within 3 months before screening.

Is the VLP Peanut treatment safe for humans?

The VLP Peanut treatment is currently being tested in a Phase I clinical trial, which is an early stage of testing in humans to assess safety. This trial follows a GMP-compliant (Good Manufacturing Practice) process, which ensures the product is made safely and consistently. ^{1 2 3 4 5}

What makes the VLP Peanut treatment unique for peanut allergy?

The VLP Peanut treatment is unique because it uses virus-like particles (VLPs) derived from cucumber mosaic virus, which are genetically fused with a major peanut allergen to create a vaccine that aims to provide long-lasting protection against peanut allergy. This approach is different from traditional allergy treatments as it focuses on immunization to prevent allergic reactions rather than just managing symptoms. ^{1 2 6 7 8}

Research Team

Pieter-Jan De Kam, PhD

Principal Investigator

Allergy Therapeutics

Eligibility Criteria

This trial is for healthy individuals and those with peanut allergy, aged 18-50, who can consent to participate. Women must not be pregnant or breastfeeding and should follow birth control guidelines if of childbearing potential. Excluded are those with severe anaphylaxis history to other allergens, certain skin conditions, inability to receive epinephrine, recent participation in another trial or substance abuse.

Inclusion Criteria

I am able to understand and sign the consent form.

I am between 18 and 50 years old.

Good general health, as determined by the Investigator

Exclusion Criteria

Participation in a clinical research trial with any investigational drug/placebo within 3 months of screening (Visit 1) or concomitantly with this clinical trial

Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the clinical trial site, Sponsor, Sponsor's representative, or another individual who has access to the clinical trial protocol

History of severe or life-threatening anaphylactic reactions to peanut resulting in neurological compromise or requiring mechanical ventilation

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 ascending subcutaneous administrations of VLP Peanut

14-18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• VLP Peanut (Virus Therapy)

Trial Overview The study tests VLP Peanut's safety and how well it's tolerated in both healthy people and those allergic to peanuts. It also examines the immune response it triggers. Participants will either receive the VLP Peanut or a placebo without active ingredients.

Participant Groups

Group I: Part B - Cohorts 1-4 Experimental Treatment 2 Interventions

4 parallel cohorts (1-4) of peanut allergic subjects. Each cohort will receive 6 ascending subcutaneous administrations of VLP Peanut.

Group II: Part A - Group A2 Experimental Treatment 1 Intervention

Adult peanut allergic subjects, will undergo skin prick tests with ascending concentrations of VLP Peanut.

Group III: Part A - Group A1 Experimental Treatment 1 Intervention

4 parallel cohorts (1-4) of adult healthy subjects. Each cohort will receive 6 ascending subcutaneous administrations of VLP Peanut.

Who Is Running the Clinical Trial?

Allergy Therapeutics

Lead Sponsor

Trials

26

Recruited

4,900+

Findings from Research

The novel vaccine candidate VLP Peanut, which combines virus-like particles with peanut allergen components, has shown to induce a strong immune response in both naïve and peanut-sensitized mice without causing allergic reactions.

VLP Peanut not only provides protection against peanut allergens but also alleviates allergic symptoms upon exposure, demonstrating its potential as a preventive immunotherapy for peanut allergy, and it has progressed to clinical development in the study PROTECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The next generation virus-like particle platform for the treatment of peanut allergy. Sobczak, JM., Krenger, PS., Storni, F., et al.[2023]

The VLP Peanut vaccine, which combines virus-like particles with peanut allergen Ara h 2, shows that the presence of prokaryotic RNA is crucial for generating strong immune responses, specifically through TLR 7 signaling, which enhances the production of high-avidity IgG antibodies.

A strong correlation was found between the density of Ara h 2 antigens on the VLP Peanut particles and the vaccine's effectiveness, indicating that both RNA content and antigen density are critical factors for the vaccine's immunogenicity and protective capacity against peanut allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy. Krenger, PS., Josi, R., Sobczak, J., et al.[2023]

After one year of peanut oral immunotherapy (P-OIT), 78.6% of preschoolers showed desensitization, successfully passing a follow-up food challenge with 4000 mg of peanut protein.

For those who did react during the follow-up, their reaction threshold increased significantly by an average of 3376 mg, indicating that P-OIT effectively enhances tolerance and may protect against accidental peanut exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy. Soller, L., Abrams, EM., Carr, S., et al.[2021]

In a real-world study involving 270 preschool children undergoing peanut oral immunotherapy (P-OIT), 90% successfully reached the maintenance dose, indicating high treatment adherence and efficacy.

The majority of reactions during treatment were mild, with only 4.1% of patients requiring epinephrine, suggesting that P-OIT is generally safe, although there is a small risk of severe reactions in some individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Real-World Safety Analysis of Preschool Peanut Oral Immunotherapy. Soller, L., Abrams, EM., Carr, S., et al.[2020]

In a phase 1 trial involving 15 participants (5 healthy adults and 10 peanut-allergic adults), the rectal administration of the modified peanut protein vaccine EMP-123 showed no significant adverse effects in healthy volunteers, but 50% of peanut-allergic subjects experienced adverse reactions, including severe allergic reactions in 20%.

Despite the adverse reactions, the treatment led to significant reductions in peanut skin test responses and basophil activation, indicating some immunologic effects, although no significant changes were observed in total IgE or peanut-specific IgE levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. Wood, RA., Sicherer, SH., Burks, AW., et al.[2021]

Ara h 1-reactive CD4(+) T cells were found in all tested subjects with peanut allergy, indicating a consistent immune response to the peanut allergen.

These T cells predominantly expressed CCR4 and produced various cytokines, including IL-4, suggesting their role in the allergic response, and the use of class II tetramers allows for effective tracking of these cells during immunotherapy without needing to expand them in the lab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ara h 1-reactive T cells in individuals with peanut allergy. DeLong, JH., Simpson, KH., Wambre, E., et al.[2021]

Virus-like particles (VLPs) derived from Turnip mosaic virus (TuMV) can be genetically engineered to carry allergens like Pru p 3, showing promise as a safe and effective treatment for food allergies, as demonstrated in a mouse model.

The VLP-Complex formulation was able to reduce allergic response markers without causing toxicity, indicating its potential as a non-hazardous immunomodulatory therapy for immune-based conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines. Pazos-Castro, D., Margain, C., Gonzalez-Klein, Z., et al.[2023]

Patients with peanut allergy (PA) exhibited a unique population of peanut-responsive CD4+ T cells that showed a heterogeneous pattern of TH2 differentiation, which was not present in healthy controls or high-threshold subjects.

The study found that these TH2 cells in PA patients produced multiple cytokines associated with allergic responses, indicating a complex immune response beyond just IgE production, and highlighted a significant role of regulatory T cells in modulating this response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets. Chiang, D., Chen, X., Jones, SM., et al.[2020]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

The next generation virus-like particle platform for the treatment of peanut allergy. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy. [2023]

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

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy. [2021]

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

First Real-World Safety Analysis of Preschool Peanut Oral Immunotherapy. [2020]

5. Denmark pubmed.ncbi.nlm.nih.gov

A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. [2021]

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

Ara h 1-reactive T cells in individuals with peanut allergy. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines. [2023]

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

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets. [2020]