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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Innoup Farma S.L.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

InnoUP Farma SL

External identifiers

EU CT number

2024-518501-17-00

EudraCT number

2018-003665-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety

Part A: Dose-ranging study (dose escalation): To determine the MTD and the recommended oral dose of INP20 in repeated-dose oral administration to patients with peanut allergy. The safety and tolerability of rising oral doses of INP20 will be assessed to identify a safe dose range for Phase II assay.
Part B: Parallel Group Extension study: To evaluate the safety and tolerability of INP20 in repeated-dose oral administration at the recommended dose(s) in patients with peanut allergy throughout the treatment period of 6 months.

Secondary objectives 3

1. Part A: Dose-ranging study (dose escalation): Pharmacodynamics.
2. Part B: Parallel Group Extension study: Potential efficacy.
3. Part B: Parallel Group Extension study: Immunogenicity.

Conditions and MedDRA coding

Peanut allergy

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 12 years and above of either sex, any race, any ethnicity at the time of the initial visit.
2. The presence of specific IgE to peanuts (a positive skin prick test to peanuts (diameter of wheal > 3.0 mm) and a positive peanut IgEs [CAP-FEIA] > 0.35 kUA/L.
3. A history of significant clinical symptoms (urticaria, angioedema, rhinorrhea, nasal congestion, pruritus, 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 after ingesting peanuts or history of unknown tolerance to peanut due to consumption avoidance.
4. Have a positive DBPCFC to peanut at a cumulative dose of less than 8.5565 grams of peanut protein.
5. Provide signed informed consent for the participation in the study. In males and females aged 12-17 years old the informed consent will be signed and dated by them, and also by the parent(s) or the subject's legally acceptable representative(s).
6. Have self-injectable epinephrine available at home and be trained on its proper use.
7. Potentially fertile women (defined as all women physiologically capable of becoming pregnant) must agree to be sexually inactive or to use appropriate contraceptive measures for the duration of the study and for 1 month afterward.
8. Patients rolling from part A to part B must have recovered their baseline levels of IgG4.

Exclusion criteria 21

1. History of severe anaphylaxis to peanut as defined by respiratory distress with cyanosis, hypoxemia (O2 Sat <92%) or, in the absence of other clinical records, severe dyspnea; hypotension with or without loss of consciousness; or relaxation of sphincters.
2. Poorly controlled Asthma as defined using the Control Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma.
3. Prior intubation/mechanical ventilation for asthma.
4. Chronic gastrointestinal diseases including Celiac Disease, Inflammatory Bowel Disease, Eosinophilic Gastrointestinal Disorders, Irritable Bowel Syndrome, gastric or intestinal cancer, diverticulitis and active peptic ulcer or recurrent gastrointestinal symptoms of undiagnosed etiology in the past year.
5. Primary or secondary immunodeficiency, including IgA deficiency; HIV positive, or immunopathology of any kind.
6. History of other chronic diseases (except asthma, rhinitis, atopic dermatitis) and severe requiring treatment (type I diabetes or uncontrolled type 2 diabetes, uncontrolled hypertension, heart disease, etc.); malignancies or serious psychological disorders.
7. Have a severe reaction at initial double-blind placebo-controlled food challenge, defined as either: - Life-threatening anaphylaxis (with severe hypotension and/or severe bronchospasm), or - Reaction requiring hospitalization.
8. Inability to discontinue antihistamines for 7 days before skin testing and oral food challenges (OFCs).
9. Patients diagnosed with other serious food allergies defined as those who have required intubation and/or ICU admission.
10. Chronic use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors, proton pump inhibitors, H2-bloquers, prokinetic drugs and laxatives.
11. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 1 month after stopping medication) who are pregnant, planning to become pregnant, or breastfeeding.
12. Currently participating in another study using an investigational new drug.
13. Participation in any interventional study, specific oral or sublingual immunotherapy building up phase for the treatment of food allergy in the past 12 months. Patients in treatment with specific oral maintenance phase of OIT will be considered individually, to investigator’s discretion.
14. Use within the past year of any systemic immunomodulatory treatment (i.e. cyclosporine, omalizumab, etc.), including inhalants immunotherapy building up phase. It is allowed the use of immunotherapy in the maintenance dosing against pollens, mites, animal dander and/or alternaria
15. Allergic to placebo ingredients or reacts to any dose of placebo during study entry double blind placebo-controlled food challenge (DBPCFC).
16. Patients allergic to corn food.
17. Poor control or persistent activation of severe atopic dermatitis.
18. Moderate to severe persistent asthma as defined using the Impairment or Risk Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma). 9.
19. Currently being treated with greater than medium daily doses of inhaled corticosteroids (fluticasone >500 μg per day, ciclesonide >400 μg per day or budesonide >800 μg per day) or montelukast. Two or more systemic corticosteroid courses for asthma in the past year or 1 oral corticosteroid course for asthma within 3 months prior to the enrollment or between the enrollment and the beginning of treatment.
20. Highly effective contraception methods include: a) total abstinence (when this is in line with the preferred and usual lifestyle of the patient); b) total sterilization (bilateral oophorectomy with/without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study treatment; c) male sterilization at least 6 months prior to screening; d) use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%) such as hormonal vaginal ring or transdermal hormone contraception. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study may also exclude a participant from the study.
21. Poor compliance expected by the patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 11

1. Part A: Dose-ranging study (dose escalation): Incidence of adverse events (AEs), serious adverse events (SAEs), treatment-related AEs/SAEs, and AEs/SAEs leading to discontinuation will be calculated and classified by body system and preferred term using MedDRA dictionary and EAACI guidelines criteria.
2. Part A: Dose-ranging study (dose escalation): Systemic allergic symptoms and relatedness to treatment.
3. Part A: Dose-ranging study (dose escalation): Physical examination and vital signs.
4. Part A: Dose-ranging study (dose escalation): Peak flow.
5. Part A: Dose-ranging study (dose escalation): Biological safety (laboratory): hematology, coagulation, biochemistry, urinalysis, and immunologic tests.
6. Part A: Dose-ranging study (dose escalation): Number of participants with Dose-limiting toxicities (DLT).
7. Part B: Parallel Group Extension study: Incidence of adverse events (AEs), serious adverse events (SAEs), treatment-related AEs/SAEs, and AEs/SAEs leading to discontinuation will be calculated and classified by body system and preferred term using MedDRA dictionary and EAACI guidelines criteria.
8. Part B: Parallel Group Extension study: Systemic allergic symptoms and relatedness to treatment.
9. Part B: Parallel Group Extension study: Physical examination and vital signs.
10. Part B: Parallel Group Extension study: Peak flow.
11. Part B: Parallel Group Extension study: Biological safety (laboratory): hematology, coagulation, biochemistry, urinalysis, and immunologic tests.

Secondary endpoints 3

1. Part A: Dose-ranging study (dose escalation): The change in Immunoglobulin G subtype (IgG4) (as biomarkers of immunogenicity of allergen-specific immunotherapy) at the end of treatment and at month 1, month 2 and month 3.
2. Part B: Parallel Group Extension study: To detect differences in increases in reaction thresholds (challenge scores) to peanut of treatment groups versus the placebo after 6 months of INP20 treatment. Challenges scores will be measured by the amount of cumulative peanut protein participants are able to ingest successfully without symptoms of an allergic reaction.
3. Part B: Parallel Group Extension study: Outcome variables of interest will include peanut specific IgE, IgG, and IgG4 response against complete extract and some allergenic components of peanut; specific basophil activation against NP, NP-peanut and peanut raw extract; mast cell responses through skin prick testing and endpoint titration; and specific T-cell cytokine responses (IL10, TGF-beta, IL4, IL5 and IL13) and T regulatory cell (Treg) activation (subpopulation Treg1 CD4+ CD25+).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Innoup Farma S.L.

Sponsor organisation

Innoup Farma S.L.

Address

Plaza Cein 5, Noain C Noain C

City

Noain (Valle De Elorz)

Postcode

31110

Country

Spain

Scientific contact point

Organisation

Innoup Farma S.L.

Contact name

Maite Agüeros

Public contact point

Organisation

Innoup Farma S.L.

Contact name

Maite Agüeros

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications