REGN5713-5715 for Allergic Conjunctivitis

Recruiting at 2 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Antibiotics, Antivirals, Antifungals

Disqualifiers: Severe allergies, Chronic infections, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is researching 2 experimental drugs, REGN5713 and REGN5715, which are called REGN5713-5715 when mixed together (called "study drug") to reduce eye allergy signs and symptoms due to birch tree pollen allergy. The aim of the study is to see how safe and effective the study drug is at lowering allergic eye signs and symptoms compared with placebo. A placebo looks like a treatment but does not contain any real medicine. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a persistent infection requiring treatment with systemic antibiotics, antivirals, or antifungals, you may be excluded from the trial.

What data supports the idea that REGN5713-5715 for Allergic Conjunctivitis is an effective treatment?

The available research shows that vaccines based on the major birch pollen allergen Bet v 1, which is related to REGN5713-5715, have been effective in reducing allergy symptoms. In clinical trials, these vaccines improved symptoms and modified the immune response in patients allergic to birch pollen. Specifically, a phase II trial showed that vaccination with a similar treatment reduced symptoms like itchy eyes and the need for additional medication compared to a placebo. This suggests that REGN5713-5715 could be an effective treatment for allergic conjunctivitis. ^{1 2 3 4 5}

What safety data exists for REGN5713-5715 in treating allergic conjunctivitis?

The research does not provide specific safety data for REGN5713-5715 or Anti-Bet v 1 monoclonal antibodies. However, it discusses the use of recombinant Bet v 1 vaccines, which are related to the treatment of birch pollen allergies. These vaccines have been shown to improve allergic symptoms and modify immune responses favorably in clinical trials, suggesting potential safety and efficacy. No direct safety data for REGN5713-5715 is mentioned. ^{1 2 4 6 7}

Is the drug REGN5713-5715 a promising treatment for Allergic Conjunctivitis?

Yes, REGN5713-5715 is a promising drug for Allergic Conjunctivitis because it targets Bet v 1, a major allergen in birch pollen, which is a common cause of allergies. By using monoclonal antibodies, it can potentially reduce allergic reactions and improve symptoms for people with allergies. ^{1 2 3 4 8}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

Adults with a history of moderate to severe birch pollen allergy for at least 2 years, bothersome eye symptoms during birch season, and positive tests for specific allergic responses (skin prick test and immunoglobulin E) can join. Those who don't meet the screening criteria or have conditions that might interfere with the study are excluded.

Inclusion Criteria

I have had severe birch pollen allergies with eye symptoms for over 2 years.

I am allergic to birch pollen.

I tested positive for birch and Bet v 1 allergies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REGN5713-5715 or placebo to assess efficacy and safety in reducing allergic conjunctivitis symptoms

16 weeks

Multiple visits including baseline and Day 8 assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• REGN5713-5715

Trial Overview The trial is testing REGN5713-5715, a combination of two experimental drugs aimed at reducing eye allergy symptoms from birch pollen compared to a placebo—a treatment lookalike without active medicine. It will also measure drug levels in blood and check if the body develops antibodies against it.

Participant Groups

Group I: REGN5713-5715 Experimental Treatment 2 Interventions

Participants will be randomized 1:1

Group II: Placebo Placebo Group 1 Intervention

Participants will be randomized 1:1

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Different production methods for the low IgE binding isoform of the birch pollen allergen Bet v 1 can significantly affect its immunological properties, which is crucial for developing effective allergy treatments.

The study highlights that optimizing the production of recombinant allergens is essential for improving allergen-specific immunotherapy (SIT) outcomes, as variations in protein characteristics can influence their clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of recombinant production on the immunologic behavior of birch pollen isoallergens. Wallner, M., Himly, M., Neubauer, A., et al.[2021]

Recombinant Bet v 1 vaccines have been developed as a targeted treatment for birch pollen allergies, showing significant improvement in allergic symptoms and immune response in clinical trials.

In a phase II trial, patients receiving rBet v 1 experienced reduced symptoms of rhinoconjunctivitis and needed less rescue medication compared to those receiving a placebo, indicating its efficacy as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Bet v 1 vaccine for treatment of allergy to birch pollen. Grönlund, H., Gafvelin, G.[2019]

Five human monoclonal antibodies specific to the birch pollen allergen Bet v 1 were characterized, showing a high degree of somatic mutations that suggest they underwent an affinity maturation process after immunotherapy.

While one antibody (BAB1) effectively inhibited IgE binding to Bet v 1, another (BAB2) actually increased IgE recognition and enhanced allergic reactions, highlighting the complexity and unpredictability of immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction. Denépoux, S., Eibensteiner, PB., Steinberger, P., et al.[2019]

A specific monoclonal antibody (mAb), Bip 1, was characterized and found to enhance IgE binding to the allergen Bet v 1, indicating that it may stabilize certain conformations of the allergen that are more recognizable to the immune system.

This study suggests that allergic patients have a diverse range of IgE antibodies targeting different forms of Bet v 1, highlighting a potential new mechanism for how immune responses to allergens are regulated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of Bip 1, a monoclonal antibody that modulates IgE binding to birch pollen allergen, Bet v 1. Laffer, S., Vangelista, L., Steinberger, P., et al.[2014]

All examined birch species contain multiple PR-10 genes, with a total of 134 unique sequences identified, indicating a diverse genetic background that may contribute to allergenic potential.

The study found that birch species, particularly Betula pendula, express a mixture of Bet v 1 isoforms, including both highly allergenic and hypoallergenic types, suggesting that most birch species could pose a risk for Bet v 1-related allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen. Schenk, MF., Cordewener, JH., America, AH., et al.[2021]

Vaccination with hypoallergenic Bet v 1 derivatives, particularly the Bet v 1 trimer, significantly increases the levels of Bet v 1-specific IgG antibodies, which can inhibit the binding of allergen-IgE complexes to B cells, potentially reducing allergic responses.

The study involved 46 patients and demonstrated that the trimer group showed a statistically significant reduction in IgE binding to CD23 compared to placebo, indicating that this vaccination strategy may effectively modulate allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules. Pree, I., Shamji, MH., Kimber, I., et al.[2021]

IgE antibodies from birch pollen allergic patients primarily recognize conformational epitopes of Bet v 1, while IgG antibodies from both allergic and non-allergic individuals mainly target unfolded and sequential epitopes, indicating a difference in how these antibodies interact with the allergen.

Natural Bet v 1-specific IgG antibodies do not effectively inhibit IgE binding to Bet v 1 and may even enhance basophil activation, suggesting that these IgG antibodies do not provide protection against allergic reactions and have a different origin compared to IgE antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes. Brazhnikov, G., Smolnikov, E., Litovkina, A., et al.[2023]

A study of 14 patients allergic to European chestnut pollen revealed that 92% had IgE antibodies binding to a 22 kD protein, indicating its potential role as a major allergen in Type I allergies.

The research demonstrated that both the 22 kD and 14 kD proteins from European chestnut pollen share common allergenic structures with birch pollen allergens, suggesting cross-reactivity and aiding in the understanding of pollen allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergens from birch pollen and pollen of the European chestnut share common epitopes. Hirschwehr, R., Jäger, S., Horak, F., et al.[2019]

References

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

The influence of recombinant production on the immunologic behavior of birch pollen isoallergens. [2021]

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

Recombinant Bet v 1 vaccine for treatment of allergy to birch pollen. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction. [2019]

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

Molecular characterization of Bip 1, a monoclonal antibody that modulates IgE binding to birch pollen allergen, Bet v 1. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules. [2021]

7. Denmark pubmed.ncbi.nlm.nih.gov

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Allergens from birch pollen and pollen of the European chestnut share common epitopes. [2019]