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

Sanofi

Status and phase: Completed; Phase 1

Conditions: Food Allergy

Treatments: Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE); Drug: Placebo for GLA; Drug: Glucopyranosyl Lipid A (GLA); Drug: Placebo for SLIT PE

Study type: Interventional

Funder types: Industry

Identifiers

NCT03463135

TDR14287

U1111-1200-1824 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 27 patients

Sex: All

Ages: 12 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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27 participants in 3 patient groups, including a placebo group

SAR439794 [PE SLIT + GLA)]

Experimental group

Description:

GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks

Treatment:

Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE)

Drug: Glucopyranosyl Lipid A (GLA)

Placebo for GLA + SLIT PE

Experimental group

Description:

Placebo for GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks

Treatment:

Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE)

Drug: Placebo for GLA

Placebo for GLA + Placebo for SLIT PE

Placebo Comparator group

Description:

Placebo for GLA repeated doses then Placebo for SLIT PE escalating doses once daily for 12 weeks

Treatment:

Drug: Placebo for SLIT PE

Drug: Placebo for GLA