HAL-MPE1 Safety and Tolerability Study

Study Overview
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Brief Summary
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The aim of this study is to confirm safety and tolerability of incremental doses of HAL-MPE1 subcutaneous immunotherapy (SCIT) in peanut allergic adults, and subsequently assess the safety and tolerability in adolescents and children with peanut allergy.

Detailed Description
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At the time of the study there was no effective treatment available for peanut allergy other than avoidance of peanut allergens. There was high unmet medical need for a disease modifying treatment for peanut allergy, especially for peanut allergic children, since this age group is at highest risk of peanut-related anaphylaxis requiring hospitalization. A chemically modified, aluminum hydroxide adsorbed peanut extract (HAL-MPE1) for subcutaneous administration has been developed. The safety and tolerability of HAL-MPE1 have been established in a First-in-human (FIH) study in adults.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-centre Study to Assess the Safety, Tolerability and Immunologic Effects of HAL-MPE1 Subcutaneous Immunotherapy in Adult and Paediatric Subjects With Peanut Allergy

Conditions
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Peanut Allergy

Intervention / Treatment
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* Biological: HAL-MPE1
* Drug: HAL-MPE1 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent/assent Male or female subjects aged 5- 50 years A well-documented medical history of systemic reactions after ingestion of peanut Positive serum specific anti-peanut (>5.0 kU/L) and Ara h 2 Immunoglobulin E (IgE)-test (>2.0 kU/L) Skin prick test (SPT) to peanut ≥3 mm compared to negative control within the last 2 years Forced expiratory volume at first second (FEV1)>80% predicted (adults and adolescents) or Peak expiratory flow(PEF)>80% predicted (children) Negative pregnancy test at screening for females of childbearing potential Females of childbearing age must be using an effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Contraceptive measures considered adequate are: hormonal contraceptives such as contraceptive pills, transdermal patches, intrauterine device (IUD), intrauterine system (IUS) implant, or vaginal ring (started - least 4 weeks prior to Investigational Medicinal Product (IMP) administration) double barrier methods: e.g. condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent surgical sterilization of the female participant (removal of the uterus or ovaries or tubal ligation) participants who are postmenopausal (12 consecutive months without a period) for at least 2 years male partner sterilization (vasectomy with documentation of azoospermia) prior to the female patient's entry into trial and is the sole sexual partner for that female patient sexual abstinence or having no sexual relationship with a man. Exclusion Criteria: Subjects with a history of severe anaphylaxis to peanut with the following symptoms: hypotension, neurological compromise (collapse, loss of consciousness or incontinence) after ingestion of peanuts Baseline serum tryptase level >20 µg/l Known allergy or hypersensitivity to an excipient in the study drug or placebo Clinical features of moderate or severe persistent asthma (as guided by the 2007 NHLBI Guidelines and according to the opinion of the investigator) Asthma with FEV1<80% predicted (adults, adolescents) or PEF <80% predicted (children) Asthma Control Test (ACT) ≤ 19 Asthma attack/exacerbation within the last 3 months Hospitalization due to asthma within the last year Two or more courses of oral steroids within the last 6 months History of intubation /mechanical ventilation due to allergies or asthma Participation in any interventional study with peanut immunotherapy in the last year Any specific immunotherapy (SCIT, Sublingual Immunotherapy (SLIT) or OIT) during the study period Severe immune disorders (including autoimmune diseases) and/or diseases requiring immunosuppressive drugs Presence of chronic urticaria, atopic dermatitis with flare or atopic dermatitis with SCORAD>40 Active malignancies or any malignant disease within the past 5 years Severe (uncontrolled) diseases that could increase the risk for subjects participating in the study, including but not limited to: any severe or unstable lung diseases; endocrine diseases; clinically significant renal or hepatic diseases, renal impairment, haematological disorders; severe ongoing symptomatic allergic diseases History of cardiovascular disease, uncontrolled hypertension or arrhythmias Diseases with a contraindication for the use of epinephrine (e.g. hyperthyroidism, glaucoma) Use of systemic steroids within 4 weeks before start of the study and during the study Treatment with beta-blockers or angiotensin-converting enzyme (ACE) inhibitors Vaccination within one week before start of therapy or during study unless considered necessary based on the opinion of the investigator. Anti-IgE/anti-Tumor Necrosis Factor (TNF)/omalizumab therapy or any biologic immunomodulatory therapy within the 6 months prior to inclusion and during the study Participation in a clinical study with a new investigational drug within the last 3 months or for a biological within the last 6 months prior to or during the study For female adolescents and adults of childbearing potential: Pregnancy (test performed at screening), lactation or inadequate contraceptive measures for women of child-bearing age (contraceptive measures considered adequate are: intrauterine devices, hormonal contraceptives, such as contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release, sexual abstinence or having no sexual relationship with a man) Alcohol, drug or medication abuse within the past year Any clinically significant abnormal laboratory parameter at screening Lack or expected lack of cooperation or compliance Unable to use the epinephrine pen correctly Severe psychiatric, psychological, or neurological disorders Subjects who are employees of the sponsor, institution or 1st degree relatives or partners of the investigators

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 50 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: HAL-MPE1<br>HAL-MPE1 is an off-white to white liquid suspension containing modified peanut extract | Biological: HAL-MPE1<br>* Weekly subcutaneous administrations of HAL-MPE1<br>* Other names: Modified peanut extract;|
| Placebo Comparator: HAL-MPE1 placebo<br>HAL-MPE1 placebo without modified peanut extract | Drug: HAL-MPE1 placebo<br>* Weekly subcutaneous administrations of HAL-MPE1 placebo<br>* Other names: Placebo for modified peanut extract;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of local and systemic reactions | Occurrence of immediate (≤ hour), early (1-4) and late (> 4 hours) local and systemic reactions reactions | within 30 minutes to >4 hours | 
| Occurrence of treatment emergent adverse events | Treatment emergent adverse events will be collected by reporting of adverse events and by clinical relevant changes in laboratory values, vital signs, lung function and aluminum levels in plasma and urine | Throughout study completion, an average 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes immunoglobulin levels | Serum specific and component specific immunoglobulin levels | Before and after 4, 8 and 16 weeks of treatment | 
| Changes in basophil activation | In vitro determination of basophil activation upon antigen stimulation | Before and after 16 weeks treatment | 
| Changes in histamine release test | Determination of histamine release and total cellular histamine content induced by peanut | Before and after 16 weeks treatment |