A Study to Assess Primarily the Tolerability and Safety of SAR439794 After Repeated Sublingual Daily Administration in Peanut Allergic Adult and Adolescent Patients

Study Overview
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Brief Summary
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Primary Objective: To assess tolerability and safety of SAR439794 [peanut extract (PE) sublingual immunotherapy (SLIT) adjuvanted with Glucopyranosyl Lipid A (GLA)] after repeated sublingual (SL) daily administration in peanut allergic adult and adolescent patients. Secondary Objective: To assess pharmacodynamics of SAR439794 after repeated SL daily administration in peanut allergic adult and adolescent patients.

Detailed Description
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The total study duration per participant is approximately from 15 to 18 weeks (core study) from screening until end-of-study visit, and 2 phone calls at Week 26 and Week 52 after the last Investigational Medicinal Product (IMP) dose.

Official Title
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A Randomized, Multicenter, 3-arm, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacodynamics of Repeated Sublingual Daily Administration of SAR439794 in Peanut Allergic Adult and Adolescent Patients

Conditions
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Food Allergy

Intervention / Treatment
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* Drug: Glucopyranosyl Lipid A (GLA)
* Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE)
* Drug: Placebo for GLA
* Drug: Placebo for SLIT PE


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or female patients, between 18 and 55 years of age, inclusive and adolescents between 12 and 17 years of age (after enrollment of 20 adult patients completed the 6 weeks dose escalation period and the safety and tolerability is deemed acceptable). Physician-diagnosed peanut allergy OR convincing history of objective clinical symptoms consistent with immediate hypersensitivity within 4 hours following known ingestion of peanuts or peanut-containing food AND by the following combined criteria: Peanut-specific IgE (P-sIgE) >5 kUA/L and Arah2-specific IgE (Arah2-sIgE) >2 kUA/L, Skin Prick Test (SPT) to peanut allergen ≥5 mm compared to saline control. High-sensitivity C reactive protein (hs-CRP), fibrinogen and neutrophil count within laboratory normal range unless the Investigator considers an abnormality to be clinically irrelevant. Ability to perform spirometry based on the American Thoracic Society guidelines. Patient must be trained on the proper use of an injectable epinephrine device and should be able to use it. Exclusion criteria: Any history or presence of autoimmune, cardiovascular disease, chronic lung disease, malignancy, psychiatric illness, or gastrointestinal inflammatory conditions, including celiac disease, inflammatory bowel disease and eosinophilic gastrointestinal disorders. History of severe anaphylaxis, documented hypotension, neurological compromise (confusion, loss of consciousness), or incontinence known or suspected to be caused by ingestion of peanut or that required treatment with 2 or more administrations of epinephrine or hospitalization. Daily oral steroid use for >1 month during the past year, burst oral steroid course in the past 6 months, or >1 burst oral steroid course in the past year. Asthma requiring >1 hospitalization in the past year or >1 emergency department visit in the past 6 months. Severe or poorly controlled atopic dermatitis. Diagnosis of eosinophilic esophagitis. Diagnosis of other severe or complicating medical problems. Primary immune deficiency. If female, pregnancy (defined as positive β-HCG [human chorionic gonadotropin] blood test), breastfeeding. If female of childbearing potential, unable to use an effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. Use of beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or monoamine oxidase inhibitors. Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development. Any patient who cannot be contacted in case of emergency. Any patient who is the Investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis B virus core antibodies (anti-HBc Ab), anti-hepatitis C virus antibodies (anti-HCV Ab), anti-human immunodeficiency Virus 1 and 2 antibodies (anti-HIV1 and anti- HIV2 Ab). Presence of sublingual epithelium and oral mucosa wound or infection (abcess, ulcer, candidiasis, gingivitis, etc.) or painful tooth decay. Participation in any food immunotherapy interventional study within the past 6 months. Patients who had received any monophosphoryl lipid (MPL)- or glucopyranosyl lipid A (GLA)-containing products within the last 6 months. Patients who experienced a Grade 3 or higher treatment emergent adverse event following administration of a MPL- or GLA-containing product. Use within the past 6 months of systemic immunomodulatory treatment and biologics with an immune target, including Xolair®. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR439794 [PE SLIT + GLA)]<br>GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks | Drug: Glucopyranosyl Lipid A (GLA)<br>* Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual<br>Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE)<br>* Pharmaceutical form:Solution Route of administration: Sublingual<br>|
| Experimental: Placebo for GLA + SLIT PE<br>Placebo for GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks | Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE)<br>* Pharmaceutical form:Solution Route of administration: Sublingual<br>Drug: Placebo for GLA<br>* Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual<br>|
| Placebo Comparator: Placebo for GLA + Placebo for SLIT PE<br>Placebo for GLA repeated doses then Placebo for SLIT PE escalating doses once daily for 12 weeks | Drug: Placebo for GLA<br>* Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual<br>Drug: Placebo for SLIT PE<br>* Pharmaceutical form:Solution Route of administration: Sublingual<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | Number of participants with AEs | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacodynamic (PD) parameter: Peanut-specific serum Immunoglobulin G (IgG) levels | Change from baseline to Day 85 in peanut-specific serum IgGs levels in patients administered with Glucopyranosyl Lipid A (GLA) + Sublingual Immuno Therapy Peanut Extract (SLIT PE) versus placebo for GLA + SLIT PE | Baseline to Day 85 | 
| Assessment of PD parameter: Peanut-specific serum IgG levels | Change from baseline to Day 57 in peanut-specific serum IgGs levels (total P-sIgGs, P-sIgG4 and P-sIgG1) in patients administered with GLA + SLIT PE versus placebo for GLA + SLIT PE | Baseline to Day 57 | 
| Assessment of PD parameter: Peanut-specific serum Immunoglobulin E (IgE) levels | Change from baseline to Day 57 and Day 85 in peanut-specific IgE in patients administered with GLA + SLIT PE versus placebo for GLA + SLIT PE | Baseline to Day 57, Baseline to Day 85 | 
| Assessment of PD parameter: Skin Prick Test | Absolute change from baseline in Skin Prick Test (SPT) to peanut allergen at Day 85 only in patients administered with GLA + SLIT PE versus placebo for GLA + SLIT PE | On Day 85 | 
| Maximum SLIT PE dose | Maximum SLIT PE dose reached by patients administered with GLA + SLIT PE versus placebo GLA + SLIT PE | On Day 85 |