Clinical Trials

Date: 2017-10-31

Type of information: Publication of results in a medical journal

phase: 2

Announcement: publication of results in The Journal of Allergy and Clinical Immunology: In Practic

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-allergic children and adolescents 4-17 years of age

Therapeutic area: Allergic diseases

Country: USA

Trial details:

• This trial is a multi-center, randomized, double-blind placebo controlled study of efficacy and safety of characterized peanut oral immunotherapy in peanut allergic individuals.(NCT01987817)

Latest news:

• • On October 31, 2017, Aimmune Therapeutics announced the online publication of positive data from its ARC001 Phase 2 clinical trial of AR101 in The Journal of Allergy and Clinical Immunology: In Practice.  The ARC001 study enrolled 55 peanut-allergic subjects, ages 4–21. The study was the first randomized, placebo-controlled Phase 2 peanut oral immunotherapy study to include double-blind, placebo-controlled food challenges at both entry and exit. The study was also the first conducted using an investigational oral biologic drug with a characterized peanut protein profile, manufactured to cGMP standards and intended for potential commercialization.
• The ARC001 study met its primary endpoint, providing evidence that AR101 has immunomodulatory activity, which, after approximately six months of treatment, significantly reduced clinical reactivity in almost 80 percent of the peanut-allergic subjects randomized to AR101 treatment.
• The primary endpoint of the Phase 2 study was the proportion of subjects in each arm able to tolerate a single highest dose of at least 300 mg of peanut protein, with no or only mild symptoms, at an exit double-blind, placebo-controlled food challenge (DBPCFC). The exit DBPCFC tested consecutive doses of 3, 10, 30, 100, 300, and 600 mg of peanut protein, given 20 to 30 minutes apart, as tolerated with no or mild symptoms.
• In the intention-to-treat (ITT) analysis, 23 of 29 AR101 subjects (79 percent) tolerated a single highest dose of at least 300 mg of peanut protein, versus 5 of 26 placebo subjects (19 percent) (p<0.0001). Additionally, 18 of 29 AR101 subjects (62 percent) tolerated a single highest dose of 600 mg of peanut protein, versus 0 of 26 placebo subjects (0 percent).
• Of the AR101 subjects who completed the desensitization protocol (n=23), all tolerated the 300-mg dose of peanut protein. Further, 78 percent of those subjects tolerated the 600-mg dose of peanut protein, corresponding to cumulative equivalents of approximately one and a half peanuts (443 mg total) and approximately three to four peanuts (1,043 mg total), respectively.
• Consistent with the known mechanisms of OIT, transient allergic symptoms occurred in nearly all AR101 subjects, with 96 percent of those symptoms being mild, not dose-limiting, and not requiring medical intervention. No adverse events were graded as severe. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events in both the AR101 and the placebo subjects. Recurrent GI symptoms led to the early withdrawal from treatment of four AR101 subjects and contributed, along with other factors, to the early withdrawal of two additional AR101 subjects. In all six AR101 subjects who withdrew (21 percent), the GI symptoms resolved within three weeks of discontinuing treatment.   • On March 6, 2017, Aimmune Therapeutics announced clinical data presented at the 2017 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Atlanta. The presentations included Phase 2 adherence data from Aimmune’s AR101 program. The Phase 2 adherence data, showing 95% adherence to daily at-home AR101 dosing in the randomized, double-blind, placebo-controlled ARC001 study, were presented in the abstract “At-home dosing adherence during characterized oral desensitization immunotherapy (CODIT) for peanut allergy” (#803, Jones S, et al.).
• AR101 is currently in Phase 3 clinical trials, with pivotal data expected in the first quarter of 2018.
• • On June 7, 2015, Aimmune Therapeutics announced that a Phase 2 study (ARC001) evaluating the company’s lead investigational product, AR101 for the treatment of peanut allergy, met its primary endpoint and additional endpoint of desensitizing patients to cumulative amounts of peanut protein of 443 mg and 1,043 mg, respectively. Of the 23 active-arm patients who completed the study, 100 percent tolerated exposure to 443 mg cumulative amounts of peanut protein, and 78 percent tolerated exposure to 1,043 mg cumulative amounts of peanut protein. Wesley Burks, M.D., chairman of the department of pediatrics at the University of North Carolina School of Medicine and physician in chief of N.C. Children’s Hospital, presented the results of the study at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2015 in a late-breaking oral abstract session titled “A novel characterized peanut allergen formulation (AR101) for oral immunotherapy (OIT) induces desensitization in peanut-allergic subjects: A Phase 2 clinical safety and efficacy study.”
• The ARC001 Phase 2 study, conducted at eight U.S. sites, evaluated the safety and efficacy of AR101 in peanut-allergic patients ages 4-21 who failed a double-blind, placebo-controlled food challenge (DBPCFC) of less than or equal to 100 mg of peanut protein. The randomized, double-blind, placebo-controlled study had 55 patients in the intent-to-treat population, with 29 in the active group and 26 in the placebo group. The active arm had six early discontinuations due to gastrointestinal side effects (which resolved within one to three weeks after cessation of treatment) and compliance issues.
• In the study, 23 of 23 patients who completed the active treatment regimen met the primary endpoint of tolerating a cumulative amount of peanut protein of at least 443 mg, compared to 5 of 26 patients receiving placebo (p?0.0001). Additionally, 18 of 23 patients who completed the active treatment regimen tolerated a cumulative amount of peanut protein of at least 1,043 mg, compared to 0 of 26 patients receiving placebo (p?0.0001). The active treatment regimen consisted of approximately 20 weeks of gradually increasing doses and two weeks of maintenance doses. For reference, one peanut kernel contains approximately 250-300 mg of peanut protein. The majority of the adverse events observed in the active arm of the study during the treatment period were mild. One serious adverse event (SAE) involving anaphylaxis was reported in the active arm and required a single administration of epinephrine.
• In the entry DBPCFC prior to the study treatment period, four patients in the active group and four patients in the placebo group had allergic reactions that required the administration of epinephrine. In the exit DBPCFC following the study treatment period, two patients in the active group had allergic reactions requiring the administration of epinephrine, compared to 11 patients in the placebo group who had allergic reactions requiring the administration of epinephrine, including three patients who required two doses. In the active group, both uses of epinephrine at exit were triggered by moderate reactions at the highest challenge dose of 600 mg, whereas in the placebo group, the uses of the epinephrine at exit were triggered by moderate or severe reactions at doses as low as 30 mg. The exit DBPCFC dose progression was: 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 600 mg, with the 300 mg dose corresponding to the cumulative dose of 443 mg and the 600 mg dose corresponding to the cumulative dose of 1,043 mg.
• Patients who completed ARC001 were eligible to participate in ARC002, an open-label study designed to evaluate the long-term safety, efficacy and tolerability of AR101.
• Aimmune Therapeutics is developing AR101 as a potential desensitization therapy for patients with peanut allergy to provide them with protection from peanut allergens at a level that substantially exceeds the amount typically encountered in an accidental exposure. AR101, which has been granted “Fast-Track” designation by the FDA, is a complex mixture of naturally occurring proteins and pharmaceutical-grade ingredients designed to enable the convenient dosing of consistent amounts of peanut protein with well-defined concentrations of peanut allergens. Patients ingest AR101 mixed with a common age-appropriate food.
• 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.
• Aimmune Therapeutics plans to initiate a Phase 3 registration trial of AR101 in children and adults with peanut allergies and Phase 2 studies of CODIT product candidates for two additional food allergies.

Is general: Yes