Study of ENP-501 in Peanut-Allergic and Non-Allergic Participants

Официальное название

A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of ENP-501 in Non-Peanut Allergic Participants and Participants With a Known Peanut Allergy

Обзор

This is a Phase 1/2 study to evaluate the safety and clinical activity of ENP-501 in non-peanut allergic (NPA) healthy participants and participants with an established peanut allergy (PA)

Вмешательства

• Препарат ENP-501
  * Part 1: Participants will receive buccal administrations of ENP-501 daily for 6-14 weeks * Part 2: Participants will receive buccal administrations of ENP-501 daily for 52 weeks following achieving the 2000 µg target dose
• Препарат Placebo
  * Part 1: Participants will receive buccal administrations of placebo daily for 6-14 weeks * Part 2: Participants will receive buccal administrations of placebo daily for 52 weeks following achieving the 2000 µg target dose

Первичные конечные точки

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by NCI CTCAE v 5.0 in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with Treatment-Emergent Serious Adverse Events (TESAEs) as Assessed by NCI CTCAE v 5.0 in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with Dose Limiting Toxicities (DLTs) as Assessed by NCI CTCAE v 5.0 in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with Systemic Reactions as Assessed by NCI CTCAE v 5.0 in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with changes in Clinical Laboratory Values in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with changes in Physical Examination in Part 1 [Срок оценки: Up to 22 Weeks]
• Number of Participants with changes in Vital Signs in Part 1 [Срок оценки: Up to 22 Weeks]
• Proportion of Participants Tolerating ≥1043 mg Cumulative Peanut Protein Without Dose-Limiting Symptoms at End of Treatment (EOT) Visit Double-Blind Placebo-Controlled Food Challenge (DBPCFC) Compared to Placebo in Part 2 [Срок оценки: Up to 72 Weeks]

Вторичные конечные точки (12)

• Number of Participants Able to Tolerate 2000 µg Dose of ENP-501 Without Experiencing Dose-Limiting Toxicity (DLT) in Part 1 [Срок оценки: Up to 22 Weeks]
• Change in Total IgE Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 1-Specific IgE Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 2-Specific IgE Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 3-Specific IgE Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 1-Specific IgG4 Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 2-Specific IgG4 Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Ara h 3-Specific IgG4 Levels in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Change in Wheal Diameter on Skin Prick Test (SPT) to Peanut in Part 1 [Срок оценки: Screening and Week 22 (EOS)]
• Proportion of Participants Tolerating at Least 443 mg Cumulative Dose of Peanut Protein Without Dose-Limiting Symptoms at EOT Visit DBPCFC Compared to Placebo in Part 2 [Срок оценки: Up to 72 Weeks]
• Proportion of Participants Tolerating at Least 2043 mg Cumulative Dose of Peanut Protein Without Dose-Limiting Symptoms at EOT Visit DBPCFC Compared to Placebo in Part 2 [Срок оценки: Up to 72 Weeks]
• Proportion of Participants Tolerating 4043 mg Cumulative Dose of Peanut Protein Without Dose-Limiting Symptoms at EOT Visit DBPCFC Compared to Placebo in Part 2 [Срок оценки: Up to 72 Weeks]

Критерии участия

Критерии включения

Part 1:

• 14-50 years of age (inclusive)
• Otherwise medically healthy and able to participate in the study
• Able to perform spirometry testing in accordance with the American Thoracic Society (ATS) guidelines (2019)
• All women of child-bearing potential, agree to either abstain from sexual activity or agree to use an adequate method of contraception for the duration of the study and for 30 days after the last dose of investigational product
• Signed and dated written informed consent from the participant and/or parent or guardian
• Signed and dated assent from participant under 18 in accordance with local IRB regulations
• Willing and able to avoid peanut and peanut contaminants for the duration of the trial

Part 1 Cohort 1 only (NPA Participants)

• No known clinical history of peanut allergy with regular exposure to peanuts in daily life, i.e ingests peanuts without symptoms
• Negative Skin Prick Test (SPT) (wheal diameter of <3 mm) to peanut

Part 1 Cohort 2 only (PA Participants)

• A documented clinical history of peanut allergy, which includes the development of symptoms (e.g., urticaria, flushing, rhinorrhea and sneezing, throat tightness or hoarseness, wheezing, vomiting) verified by a physician
• At least two of the three following requirements:

• Positive Skin Prick Test (SPT) (wheal diameter of ≥ 8 mm) to peanut
• An elevated serum peanut specific IgE level ≥ 7 kUA/L (ImmunoCAP®)
• An Ara-h2 IgE level of ≥ 2 kUA/L (ImmunoCAP®)

Part 2:

• 14 to 50 years of age (inclusive)
• A documented clinical history of peanut allergy, which includes the development of symptoms (e.g., urticaria, flushing, rhinorrhea and sneezing, throat tightness or hoarseness, wheezing, vomiting) verified by a physician
• At least two of the three following requirements at screening:

• Positive SPT (wheal diameter of ≥ 3 mm) to peanut
• Serum peanut-specific IgE level ≥ 0.7 kUA/L (ImmunoCAP®)
• An Ara-h2 IgE level of ≥ 0.5 kUA/L (ImmunoCAP®) within 1 year of enrollment
• Participant must be willing and able to complete a DBPCFC at screening and EOT (24-hours after last dose) and experience dose-limiting symptoms at or before the 300 mg challenge dose of peanut protein during a Double Blind, Placebo Controlled Food Challenge (DBPCFC) conducted in accordance with Practical Issues in Allergology, Joint United States/European Union Initiative (PRACTALL) guidelines
• Otherwise medically healthy and able to participate in the study
• Able to perform spirometry testing in accordance with the ATS guidelines (2019)
• All women of child-bearing potential, agree to either abstain from sexual activity or agree to use an adequate method of contraception for the duration of the study and for 30 days after the last dose of investigational product
• Signed and dated written informed consent from the participant and/or parent or guardian
• Signed and dated assent from participant under 18 in accordance with local IRB regulations
• Willing and able to avoid peanut and peanut contaminants for the duration of the trial

Критерии исключения

• History of severe anaphylactic event requiring mechanical ventilation or use of intravenous (IV) vasopressor drugs
• Clinically significant screening electrocardiogram (ECG) abnormality or corrected QTcF >/= 450 msec at Screening
• FEV1 value < 80% predicted at Screening
• Any hospitalization in the past year for asthma, >1 course of oral steroids for asthma in the past 6 months, or any emergency room visit in the past 6 months for asthma
• Poorly controlled atopic dermatitis
• Eosinophilic gastrointestinal disease
• Use of oral or IV corticosteroids within 30 days of Screening
• Use of tricyclic antidepressants within 6 months of Screening
• Inability to discontinue antihistamines for at least 5 half-lives before skin testing
• Use of omalizumab or other immunomodulatory therapy (not including corticosteroids) or biologic therapy within one year of Screening
• Use of any food allergen-specific or other non-traditional form of allergen immunotherapy within one year of Screening
• Use of immunosuppressive drugs within 30 days of Screening
• Use of ß-blockers (oral)
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis
• Pregnant or breast-feeding (if female)
• Behavioral, cognitive, or psychiatric disease that in the opinion of the Investigator affects the ability of the participant to understand and cooperate with the study protocol
• Known allergy to inactive ingredients of investigational product (active or placebo)
• Participation in another interventional clinical trial within 30 days of Screening or within 5 half-lives of the other IP
• Residing at the same address as another participant in this or any peanut immunotherapy study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Research Site 001 — Aurora

Идентификаторы

NCT: NCT07117669 · ENP-501-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗