PALISADE study: Phase 3 clinical trial studied PALFORZIA1,2

Duration of trial was 12 months with food challenges at entry and exit1,3

Entry DBPCFC*
Entry DBPCFC*

In-office visit with gradual increasing peanut protein dose levels ranging from 1 mg to 100 mg

Initial Dose Escalation(1 day)
Initial Dose Escalation(1 day)

In-office visit with dose gradually increasing from 0.5 mg to 6 mg

Up-Dosing(~6 months)
Up-Dosing(~6 months)

Daily home dosing with in-office dose escalation every ~2 weeks (11 levels) until 300 mg is achieved

Maintenance Dosing(6 months)
Maintenance Dosing(6 months)

Daily 300-mg dose taken at home

Exit DBPCFC
Exit DBPCFC

Primary endpoint and other study endpoints assessed; in-office visit to assess desensitization; peanut protein levels ranging from 3 mg to 1000 mg

*Entry food challenge was required only in the PALISADE study for screening. It also provided a baseline comparator for results at treatment end.

DBPCFC = double-blind, placebo-controlled food challenge.

PALFORZIA was studied in highly peanut-allergic participants1,3

All study participants had an allergic reaction at 100 mg or less of peanut protein at the entry food challenge.

Key inclusion criteria:
Clinical history of peanut allergy
pslgE of ≥0.35 kUA/L and/or mean peanut skin-prick test wheal diameter ≥3 mm larger than the negative control

Key exclusion criteria: Uncontrolled asthma, history of eosinophilic esophagitis, other eosinophilic gastrointestinal disease, or severe anaphylaxis within 60 days of screening

72% of participants reported a history of peanut-related anaphylaxis prior to enrolling in the study.

PALISADE is the largest randomized, double-blind, placebo-controlled clinical trial for peanut allergy1,2

Primary analysis population graphic

Primary efficacy analysis was in participants aged 4 through 17 years

Intent-to-treat population graphic

*Three participants were randomized in error; a total of 496 participants were exposed to ≥1 dose of study product. For placebo, 125 participants should have received placebo, but 1 did not due to withdrawal of consent. For PALFORZIA, 374 should have received treatment, but 2 did not (1 withdrawal of consent and 1 randomization error).

Reasons for participant discontinuation graphic
Completer population graphic

Primary analysis population

496 participants aged 4 through 17 years

Primary efficacy analysis was in participants aged 4 through 17 years

Intent-to-treat population

3:1 randomization ratio *

372 participants received PALFORZIA

124 participants received placebo

*Three participants were randomized in error; a total of 496 participants were exposed to ≥1 dose of study product. For placebo, 125 participants should have received placebo, but 1 did not due to withdrawal of consent. For PALFORZIA, 374 should have received treatment, but 2 did not (1 withdrawal of consent and 1 randomization error).

Reasons for participant discontinuation

Adverse event: 43 with PALFORZIA vs 3 with placebo

Withdrew consent: 31 with PALFORZIA vs 6 with placebo

Removed by investigator: 1 with PALFORZIA vs 0 with placebo

Other: 5 with PALFORZIA vs 1 with placebo

Completer population

296 participants treated with PALFORZIA were assessed for levels of desensitization

116 participants treated with placebo were assessed for levels of desensitization

    Proven to reduce the severity of allergic reactions to peanut1

    Intent-to-treat Population*

    PALFORZIA met its primary endpoint in PALISADE1,2

    Primary efficacy endpoint: The percentage of participants receiving at least 1 study dose who tolerated 600 mg of peanut protein as a single dose with no more than mild allergic symptoms in the exit DBPCFC. The DBPCFC at the end of the Maintenance Phase was used to approximate an accidental exposure to peanut.

    Palforzia vs Placebo

    Desensitization response rate, single dose
    67%(n=250/372)
    4%(n=5/124; p<0.0001)

    1000 mg dose is 8x the median amount of peanut protein that triggered an accidental allergic reaction (125 mg) in the observational MIRABEL study. This median amount was studied outside of the PALFORZIA clinical trials.4

    The maintenance dose during the study was 300 mg daily. Many participants who received PALFORZIA were able to tolerate more than 300 mg of peanut protein in the exit DBPCFC.
    1. *All study participants who received at least 1 dose of treatment, including those who discontinued the study.

    Intent-to-treat Population*

    Ready for less-severe symptoms1

    Comparison of the maximum severity of symptoms at any challenge dose of peanut protein during the exit DBPCFC

    5% of participants treated with PALFORZIA experienced severe symptoms compared with 10.5% on placebo during the exit DBPCFC.

    Maximum severity of symptoms†

    Maximum severity of symptoms comparison chart
    1. *All study participants who received at least 1 dose of treatment, including those who discontinued the study.
    2. †Participants without an exit DBPCFC were assigned the maximum severity during the screening DBPCFC, which equates to no change from screening.
    3. P-value < 0.0001; symptom severity was assigned with equally spaced scores (e.g., 0, 1, 2, and 3 for none, mild, moderate, and severe, respectively), and the difference of mean scores between the two treatment arms was tested using the Cochran-Mantel-Haenszel statistic stratified by geographic region (North America, Europe).
    4. ‡Includes severe symptoms and life-threatening or fatal reactions. No participants had symptoms considered life threatening or fatal.

    Completer Population

    The completer population consisted of participants aged 4 through 17 years in the ITT population who stayed on treatment and had an evaluable exit DBPCFC (296 PALFORZIA, 116 placebo)

    During the exit dbpcfc after 12 months in the clinical study

    96.3% of participants who received PALFORZIA were able to tolerate 300 mg of peanut protein with no more than mild symptoms (vs 8.6% for placebo)
    84.5% of participants who received PALFORZIA were able to tolerate 600 mg of peanut protein with no more than mild symptoms (vs 4.3% for placebo)
    63.2% of participants who received PALFORZIA were able to tolerate 1000 mg of peanut protein with no more than mild symptoms (vs 2.6% for placebo)

    PALFORZIA had consistent safety results across both studies.

    See Results

    References

    1. PALFORZIA [package insert]. Brisbane, CA: Aimmune Therapeutics, Inc.
    2. The PALISADE Group of Clinical Investigators: Vickery BP, Vereda A, Casale TB, et al. N Engl J Med. 2018;379:1991-2001.
    3. The PALISADE Group of Clinical Investigators: Vickery BP, Vereda A, Casale TB, et al. Protocol. N Engl J Med. 2018;379:1991-2001.
    4. Deschildre A, Elegbédé CF, Just J, et al. Clin Exp Allergy. 2016;46:610-620.
    5. The PALISADE Group of Clinical Investigators: Vickery BP, Vereda A, Casale TB, et al. Supplementary Appendix. N Engl J Med. 2018;379(suppl):1991-2001.