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

• ClinicalTrials.gov Identifier: NCT03463135
• Recruitment Status: Completed
• First Posted: March 13, 2018
• Last Update Posted: May 12, 2020
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Food Allergy	Drug: Glucopyranosyl Lipid A (GLA); Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE); Drug: Placebo for GLA; Drug: Placebo for SLIT PE	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 7, 2018
• Actual Primary Completion Date: May 8, 2019
• Actual Study Completion Date: March 10, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAR439794 [PE SLIT + GLA)]; GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks	Drug: Glucopyranosyl Lipid A (GLA); Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual; Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE); Pharmaceutical form:Solution Route of administration: Sublingual
Experimental: Placebo for GLA + SLIT PE; Placebo for GLA repeated doses then SLIT PE escalating doses once daily for 12 weeks	Drug: Sublingual Immuno Therapy (SLIT) Peanut Extract (PE); Pharmaceutical form:Solution Route of administration: Sublingual; Drug: Placebo for GLA; Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual
Placebo Comparator: Placebo for GLA + Placebo for SLIT PE; Placebo for GLA repeated doses then Placebo for SLIT PE escalating doses once daily for 12 weeks	Drug: Placebo for GLA; Pharmaceutical form:Colloidal aqueous dispersion Route of administration: Sublingual; Drug: Placebo for SLIT PE; Pharmaceutical form:Solution Route of administration: Sublingual

Outcome Measures

Primary Outcome Measures :

1. Adverse events (AEs) [ Time Frame: Up to Week 52 ]
   Number of participants with AEs

Secondary Outcome Measures :

1. Assessment of pharmacodynamic (PD) parameter: Peanut-specific serum Immunoglobulin G (IgG) levels [ Time Frame: Baseline to Day 85 ]
   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
2. Assessment of PD parameter: Peanut-specific serum IgG levels [ Time Frame: Baseline to Day 57 ]
   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
3. Assessment of PD parameter: Peanut-specific serum Immunoglobulin E (IgE) levels [ Time Frame: Baseline to Day 57, Baseline to Day 85 ]
   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
4. Assessment of PD parameter: Skin Prick Test [ Time Frame: On Day 85 ]
   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
5. Maximum SLIT PE dose [ Time Frame: On Day 85 ]
   Maximum SLIT PE dose reached by patients administered with GLA + SLIT PE versus placebo GLA + SLIT PE

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 55 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arkansas

Investigational Site Number 8400004

Little Rock, Arkansas, United States, 72202

United States, California

Investigational Site Number 8400019

Mission Viejo, California, United States, 92691

Investigational Site Number 8400008

San Diego, California, United States, 92123

Investigational Site Number 8400020

San Jose, California, United States, 95117

Investigational Site Number 8400006

Stanford, California, United States, 94305

United States, Colorado

Investigational Site Number 8400013

Denver, Colorado, United States, 80230

United States, Kentucky

Investigational Site Number 8400014

Louisville, Kentucky, United States, 40215

United States, Maryland

Investigational Site Number 8400002

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Investigational Site Number 8400001

Boston, Massachusetts, United States, 02114

United States, Minnesota

Investigational Site Number 8400009

Minneapolis, Minnesota, United States, 55402

Investigational Site Number 8400016

Minneapolis, Minnesota, United States, 55402

United States, North Carolina

Investigational Site Number 8400010

Charleston, North Carolina, United States, 29420

United States, Ohio

Investigational Site Number 8400011

Cincinnati, Ohio, United States, 45229

United States, Oregon

Investigational Site Number 8400012

Medford, Oregon, United States, 97504

United States, Washington

Investigational Site Number 8400003

Seattle, Washington, United States, 98105

United States, Wisconsin

Investigational Site Number 8400017

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03463135
• Other Study ID Numbers: TDR14287; U1111-1200-1824 ( Other Identifier: UTN )
• First Posted: March 13, 2018
• Last Update Posted: May 12, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases