A multicenter double-blind, randomized, placebo-controlled phase I/II study to determine the safety, tolerability, potential efficacy and dose finding of INP20, an oral formulation for treatment of immunotherapy in peanut-allergic patients - INP20 in peanut-allergy

INTERVENTION: Product Name: INP20 Product Code: INP20 Pharmaceutical Form: Oral powder INN or Proposed INN: Aqueous extract of roasted defatted peanut Other descriptive name: AQUEOUS EXTRACT OF ROASTED DEFATTED PEANUT Concentration unit: mg milligram(s) Concentration type: range Concentration number: 0.15‐5 Pharmaceutical form of the placebo: Oral powder Route of administration of the placebo: Oral use CONDITION: Peanut allergy ; MedDRA version: 20.1 Level: LLT Classification code 10034202 Term: Peanut allergy System Organ Class: 100000004870 Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: ; Main Objective: This phase I/II trial has two primary objectives; in phase I (part A), the primary objective is to determine the safety and tolerability of rising oral doses of INP20 administered to patients with peanut allergy. The maximum tolerated dose and the safe dose range of INP20 will be determined.; In the extension to the trial (phase II or Part B), the primary objective is to determine safety and tolerability of INP20 in repeated dose oral administration at the doses determined in phase I of the trial throughout a 6‐month treatment period.; ; Primary end point(s): Phase I of the study (Part A):; ; Incidence of treatment‐related adverse events with each dose level of INP20.; ; Number of participants with dose limiting toxicities.; ; Phase II of the study (Part B):; ; Incidence of adverse events (AEs) and serious adverse events (SAEs), and AEs/SAEs leading to discontinuation.; ; Secondary Objective: In phase I (part A) of the trial, the secondary objective is to determine the effect of rising oral doses of INP20 on a pharmacodynamic parameter, namely serum IgG4 concentrations in patients with peanut allergy.; In phase II (part B) of the trial, there are two secondary objectives; firstly, to assess the potential efficacy of the dose regimens determined in phase I of the trial versus placebo in an expanded treatment cohort after a 6 month treatment period. Secondly, to assess changes from baseline in immune parameters associated with INP20 repeat dose oral administration after 1, 3 and 6 months treatment.; ; Timepoint(s) of evaluation of this end point: Phase I of the study (Part A): continous evaluation of the primary endpoints.; ; Phase II of the study (Part B): continous evaluation of the primary endpoint.; SECONDARY OUTCOME: ; Secondary end point(s): Phase I of the study (Part A):; ; Incidence of adverse events (AEs) and serious adverse events (SAEs), and AEs/SAEs leading to discontinuation.; ; Incidence of systemic allergic symptoms and relatedness to treatment.; ; Other safety parameters (vital signs, results of physical examinations, clinical chemistry, haematological parameters, immunological tests).; ; Changes in IgG subtype (IgG4).; ; Basophil activation as assessed by basophil activation test (BAT).; ; Phase II of the study (Part B):; ; Safety parameters (results of physical examinations, haematological parameters, clinical chemistry).; ; Systemic allergic symptoms and relatedness to treatment.; ; Differences in reaction thresholds to peanut in treatment group versus placebo group in food challenge test.; ; Changes in allergen specific biomarkers (or immune parameters) associated with treatment. Parameters analysed will include: peanut‐specific IgE, IgG and IgG4 response versus complete extract and some allergenic components of peanut; specific basophil activation against nanoparticles (NP), NP‐peanut and raw peanut extract; mast cell responses through skin prick testing and endpoint titration; specific T‐cell cytokine responses (intracellular IL‐10, IL‐4, IL‐5, IL‐13 and TGF‐beta); regulatory T‐cell activation (Treg1, CD4+ and CD25+ subpopulations).; ; Timepoint(s) of evaluation of this end point: Phase I of the study (Part A):; ; AEs and SAEs ‐ continuous evaluation.; ; Allergic symptoms ‐ continuous evaluation.; ; Vital signs, IgG subtype test and basophil activation test ‐ baseline visit (day 0) and 14.; ; Physical examinations, clinical chemistry and haematological parameters ‐ screening visit (days ‐15 to ‐1) and day 14.; ; Phase II of the study (Part B):; ; Physical examinations, clinical chemistry and haematological parameters ‐ screening visit (days ‐15 to ‐1) and week 24.; ; Allergic symptoms ‐ continous evaluation.; ; Food challenge test ‐ baseline visit (day 0) and week 24.; ; Immune parameters associated with treatment ‐ baseline visit (day 0), weeks 4, 12 and 24.; INCLUSION CRITERIA: Age 12 years and above at time of initial visit (either sex, any race, any ethnicity) Presence of specific IgE to peanuts (positive skin prick test, diameter of wheal > 3.0 mm) and a positive test for the presence of peanut IgEs ([CAP‐FEIA] > 0.33 kUA/L). A history of significant clinical symptoms (urticaria, angioedema, rhinorrhea, nasal congestion, pruritis, sneezing, abdominal pain, emesis, diarrhea, wheezing, shortness of breath, lip/tongue swelling, throat itching, throat swelling or impending sense of doom) occurring within 60 minutes of ingesting peanuts. A positive food challenge test (DBPCFC) against peanut at a cumulative dose of less than 10 grams of peanut protein. Provision of signed informed consent for participation in the study. In participants aged 12–17 years the informed consent will be signed and data by the participant in addition t