Clinical Trials

Date: 2018-01-08

Type of information: update on patient enrollment

phase: 3

Announcement: update on patient enrollment

Company: Aimmune Therapeutics (USA - CA) previously Allergen Research Corporation (ARC)

Product: AR101

Action mechanism:

• immunotherapy product. AR101 is part of Aimmune Therapeutics’ approach to treating food allergies using its characterized oral desensitization immunotherapy, or CODIT™, system. The CODIT system leverages extensive independent scientific research on oral immunotherapy, or OIT, demonstrating that food allergy patients can be desensitized to exposure to food allergens by being administered well-defined, gradually increasing doses of the allergen over a period of months. Aimmune Therapeutics’ CODIT system is designed to precisely control the amount of allergen administered and follow a systematic dosing regimen that begins with very low doses of the allergen. Once a patient attains desensitization to a clinically meaningful level of food allergen, the patient continues to take a daily maintenance dose of the CODIT system product in order to maintain such desensitization.

Disease: peanut allergy

Therapeutic area: Allergic diseases

Country: Canada, Denmark, Germany, Ireland, Italy, Netherlands, Spain, Sweden, UK, USA

Trial details:

• The purpose of the Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults (PALISADE)  is to demonstrate the efficacy and safety of AR101 through reduction in clinical reactivity to peanut allergen in peanut-allergic children and adults. A total of 554 peanut-allergic patients, ages 4-49, were randomized to receive either AR101 or placebo for approximately six months of up-dosing followed by six months of maintenance therapy. (NCT02635776)

Latest news:

• • On January 8, 2018, Aimmune Therapeutics announced that the company plans to report topline results in February from its pivotal Phase 3 PALISADE trial of AR101 for peanut allergy, following the completion of the 554-subject trial in late 2017. To support regulatory filings, Aimmune also plans a data readout from the PALISADE follow-on trial, ARC004, in the third quarter of 2018.
• Aimmune continues to expect to file a Biologics License Application (BLA) for AR101 with the FDA at the end of 2018. Soon afterward, the company plans to begin a similar process in Europe, with the intention of filing a Marketing Authorisation Application (MAA) with the European Medicines Agency (EMA) in the first half of 2019.
• • On June 20, 2017, Aimmune Therapeutics reported findings from pre-randomization, preliminary clinical data collected from the European screening population of the PALISADE trial in AR101 program. The data were presented at the 2017 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Helsinki. Aimmune presented a preliminary dataset of 166 patients in Europe who underwent a screening double-blind, placebo-controlled food challenge (DBPCFC) to determine eligibility for the PALISADE trial (57% ages 4–11, 28% ages 12–17, and 15% ages 18–55; 59% male). The DBPCFC allowed a progression of doses of peanut protein up to a dose of 100 mg (1 mg, 3 mg, 10 mg, 30 mg, and 100 mg). Patients who reacted with dose-limiting symptoms at or before the 100-mg dose (“reactors”) were eligible for randomization into the trial. Observations from preliminary evaluable baseline characteristics results from these patients included the following:
• - Sixty-two percent of the subjects screened were reactors, who experienced dose-limiting symptoms in the DBPCFC at or before the 100-mg dose (median = 30 mg dose, meaning a cumulative amount of 44 mg peanut protein); 38% were “non-reactors” who consumed all doses in the DBPCFC with no dose-limiting symptoms
• - Reactors had a statistically significant larger peanut skin-prick test (SPT) wheal diameters, a higher peanut-specific IgE (psIgE) and higher Ara h 2–specific IgE than non-reactors. Ara h 2–specific IgE demonstrated greatest sensitivity and specificity for discriminating between reactors and non-reactors, based on receiver operating characteristic (ROC) curve analysis of the data
• - SPT, peanut-specific IgE and Ara h 2 were not associated with the severity of reactions during the screening DBPCFC
• • On June 12, 2017, Aimmune Therapeutics announced that, in the ongoing Phase 3 PALISADE trial of AR101, more than 97 percent of patients currently on study have completed up-dosing. Based on observations of aggregated data to date, Aimmune expects that the percentage of patients completing the entire study (up-dosing and maintenance) will be well ahead of the powering calculations behind the study design. With the vast majority of patients now successfully through up-dosing in PALISADE, Aimmune estimates that final study visits will be completed around year-end 2017, and that topline data will be available in the first quarter of 2018.
• • On March 6, 2017, Aimmune Therapeutics announced clinical data presented at the 2017 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Atlanta. A late-breaking abstract presented baseline characteristics from 583 peanut-allergic patients who were screened to determine eligibility for the Phase 3 PALISADE trial in North America. Among the inclusion criteria, a double-blind, placebo-controlled food challenge (DBPCFC) administered at screening allowed a progression of doses of peanut protein up to a dose of 100 mg (1 mg, 3 mg, 10 mg, 30 mg, and 100 mg). Subjects who reacted with dose-limiting symptoms at or before the 100 mg dose (“reactors”) were eligible for randomization into the trial. This unique dataset of screening DBPCFCs is the largest ever collected on peanut-allergic patients in the clinical trial context and yielded the following observations and insights:
• - 457 patients (78%) were reactors, who experienced dose-limiting symptoms in the DBPCFC at or before the 100 mg dose (median = 44 mg cumulative amount of peanut protein); 116 subjects (20%) were “non-reactors” who consumed all 144 mg in the DBPCFC with only mild symptoms or no symptoms at all; 10 subjects (2%) reacted to placebo
• Reactors demonstrated higher baseline peanut-specific IgE (psIgE) and Ara h2-specific IgE levels and larger peanut skin prick test (SPT) wheal diameters than non-reactors, and psIgE appeared to provide the greatest utility to discriminate between reactors and non-reactors
• The median psIgE in reactors was 70.2 kUA/L, compared with 5.3 kUA/L in non-reactors (a threshold psIgE of 19.25 kUA/L showed the greatest sensitivity and specificity for predicting reactors)
• Sensitivity to peanut and severity of symptoms during screening DBPCFCs were not closely linked, and neither was associated with baseline immune parameters or age
• Also at the AAAAI meeting, Blake Rust, Ph.D., and Erik Wambre, Ph.D., of the Benaroya Research Institute at Virginia Mason (BRI) presented data on peanut-specific effector and regulatory T cells in a blinded subset of samples from patients screened for PALISADE. Key findings from this work include:
• - Percent of activated CD4+ effector T cells were significantly higher after individuals underwent the DBPCFC as compared to their pre-challenge levels
• - At baseline, peanut-allergic individuals exhibit higher frequency of peanut-specific effector T cells relative to DBPCFC non-reactors. Peanut-allergic individuals exhibit low frequencies of peanut-specific regulatory T cells at baseline, but higher than those seen in DBPCFC non-reactors
• - Within the group of patients who reacted to the DBPCFC, two distinct immunophenotypes were observed as defined by mutually exclusive CRTH2 and CCR6 expression.
• • On February 16, 2017, Aimmune Therapeutics provides an update on ongoing AR101 phase 3 program for peanut allergy based on FDA feedback. The primary efficacy analysis in the ongoing Phase 3 PALISADE trial will now be conducted on ages 4-17 years, which aligns with the Breakthrough Therapy Designation population, based on the company’s discussions with the FDA. The company expects to conduct separate analyses for older patients in PALISADE. Additionally, based on FDA feedback, the company anticipates that the safety database for a potential Biologics License Application (BLA) will include data from at least 600 patients treated with AR101.
• The PALISADE trial enrolled 554 patients, 90 percent of whom were between ages 4-17. This age group, which represents a high-unmet need for peanut allergy therapy, is the largest segment of the 6 million peanut allergic patients in the United States and Europe.
• • On November 28, 2016, Aimmune Therapeutics announced that it has completed global enrollment of its Phase 3 PALISADE trial of AR101 for the treatment of peanut allergy, with the total randomized to the trial expected to be approximately 540 patients. Aimmune expects topline data from PALISADE in the fourth quarter of 2017, followed by regulatory submissions for marketing approval of AR101 in 2018 in both the United States and Europe. The company announced completion of North American enrollment in PALISADE in September, ahead of schedule and above target enrollment.

 

Is general: Yes