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CompletedNCT02635776PALISADEUpdated Mar 17, 2022Results posted

Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults (PALISADE)

A Phase 3 interventional study of AR101 powder provided in capsules & sachets and Placebo powder provided in capsules & sachets in Peanut Allergy, sponsored by Aimmune Therapeutics, Inc.. Completed at 69 sites in 10 countries. Open to participants aged 4 Years to 55 Years. Per ClinicalTrials.gov, last updated 2022-03-17.

Sponsored by Aimmune Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
555
Allocation
Randomized
Ages
4 Years to 55 Years
Sex
All
01

Study summary

The purpose of this study is to demonstrate the efficacy and safety of AR101 through reduction in clinical reactivity to peanut allergen in peanut-allergic children and adults.

Read the detailed description

This is an international, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of AR101 in a characterized desensitization oral immunotherapy regimen in peanut-allergic individuals.

02

Conditions studied

  • Peanut Allergy

Keywords

  • AR101 (Characterized Peanut Allergen)
  • Characterized Peanut Allergen
  • CPNA (Characterized Peanut Allergen)
  • OIT (oral immunotherapy)
  • Oral Immunotherapy
  • Peanut Allergy
  • Allergy
  • Peanut-Allergic Children
  • Peanut-Allergic Adults
  • Desensitization
03

Who can participate

Ages eligible
4 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Age 4 through 55 years
  • Clinical history of allergy to peanuts or peanut-containing foods
  • Serum immunoglobulin E (IgE) to peanut ≥0.35 kUA/L (kilos of allergen-specific units per liter, determined by UniCAP™* within the past 12 months) and/or a skin prick test (SPT) to peanut ≥3 mm compared to control
  • Experience dose-limiting symptoms at or before the 100 mg challenge dose of peanut protein (measured as 200 mg of peanut flour) on Screening DBPCFC conducted in accordance with PRACTALL** guidelines
  • Not be residing at the same address as another subject in this or any peanut OIT study

UniCAP™*: a laboratory system for routine diagnostic testing of allergy and tool for basic studies on allergens and antibodies

PRACTALL**: PRACTical issues in ALLergology Joint United States/European Union Initiative

Key Exclusion Criteria:

  • History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
  • History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of Screening DBPCFC
  • History of chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) that is, or is at significant risk of becoming, unstable or requiring a change in chronic therapeutic regimen
  • History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia or recurrent gastrointestinal symptoms of undiagnosed etiology
  • History of severe asthma (NHLBI criteria steps 5 or 6), or mild to moderate asthma (2007 NHLBI criteria steps 1-4) that is uncontrolled or difficult to control
  • History of steroid medication use
  • History of a mast cell disorder, including mastocytosis, urticarial pigmentosa, and hereditary or idiopathic angioedema
  • Developing dose-limiting symptoms in reaction to the placebo part of the Screening DBPCFC
  • Having the same place of residence as another subject in the study
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
555 participants (actual)

Study arms

  • Experimental
    AR101 powder provided in capsules & sachets

    Study product provided as peanut protein in pull-apart capsules or sachets

    Biological: AR101 powder provided in capsules & sachets

  • Placebo comparator
    Placebo powder provided in capsules & sachets

    Placebo formulation in pull-apart capsules or sachets containing only inactive ingredients

    Biological: Placebo powder provided in capsules & sachets

Interventions

  • BiologicalAR101 powder provided in capsules & sachets

    Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol

  • BiologicalPlacebo powder provided in capsules & sachets

    Study product formulated to contain only inactive ingredients for use as defined in the protocol

05

What researchers measure

Primary outcomes

  1. Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

    The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

    Time frame: 12 months

Secondary outcomes

  1. Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

    The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

    Time frame: 12 months

  2. Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

    The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

    Time frame: 12 months

  3. Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

    The maximum severity of symptoms on 4 levels: 0-None, 1-Mild, 2-Moderate, 3-Severe or higher (Severe, life threatening, fatal) observed in the DBPCFC at any dose (1000 mg or lower).

    Time frame: 12 months

06

Results

Posted Mar 17, 2022

Participant flow

Participant flow — Overall Study
MilestoneAR101Placebo
Started416139
Completed314128
Not completed10211
Withdrew: Physician decision10
Withdrew: Adverse event513
Withdrew: Withdrawal by subject417
Withdrew: Lost to follow-up40
Withdrew: Other reasons51

Outcome measures

PrimaryPercentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

Time frame:
12 months
Reported as:
Count of participants · Participants
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
ParticipantsAR101Placebo
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)2505
Statistical analysis
  • AR101 vs Placebo · Farrington-Manning test · p = <0.0001 · Risk difference (rd): 63.2 · 95% CI 53 to 73.3
SecondaryPercentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

Time frame:
12 months
Reported as:
Count of participants · Participants
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
ParticipantsAR101Placebo
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)1873
Statistical analysis
  • AR101 vs Placebo · Farrington-Manning test · p = <0.0001 · Risk difference (rd): 47.8 · 95% CI 38 to 57.7
SecondaryPercentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

The percentage of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

Time frame:
12 months
Reported as:
Count of participants · Participants
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
ParticipantsAR101Placebo
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)28510
Statistical analysis
  • AR101 vs Placebo · Farrington-Manning test · p = <0.0001 · Risk difference (rd): 68.5 · 95% CI 58.6 to 78.5
SecondaryPercentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

The maximum severity of symptoms on 4 levels: 0-None, 1-Mild, 2-Moderate, 3-Severe or higher (Severe, life threatening, fatal) observed in the DBPCFC at any dose (1000 mg or lower).

Time frame:
12 months
Reported as:
Count of participants · Participants
Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
ParticipantsAR101Placebo
None1403
Mild11935
Moderate9473
Severe or worse1913
Statistical analysis
  • AR101 vs Placebo · Cochran-Mantel-Haenszel · p = <0.0001Cochran-Mantel-Haenszel test (using equally spaced scores), stratified by region (North America, Europe)

Adverse events

Collected over 12 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AR101 (Age 4-17)0/372 (0%)8/372 (2.2%)367/372 (98.7%)
Placebo (Age 4-17)0/124 (0%)1/124 (0.8%)118/124 (95.2%)
AR101 (Age 18-55)0/41 (0%)2/41 (4.9%)40/41 (97.6%)
Placebo (Age 18-55)0/14 (0%)1/14 (7.1%)13/14 (92.9%)
Most frequent serious events
Most frequent serious events
EventAR101 (Age 4-17)Placebo (Age 4-17)AR101 (Age 18-55)Placebo (Age 18-55)
Cutaneous vasculitisSkin and subcutaneous tissue disorders0/3720/1240/411/14
Anaphylactic reactionImmune system disorders3/3720/1241/410/14
SyncopeNervous system disorders0/3720/1241/410/14
Humerous fractureInjury, poisoning and procedural complications0/3721/1240/410/14
AsthmaRespiratory, thoracic and mediastinal disorders2/3720/1240/410/14
GastroenteritisInfections and infestations1/3720/1240/410/14
Gastroenteritis viralInfections and infestations1/3720/1240/410/14
Pharyngitis streptococcalInfections and infestations1/3720/1240/410/14
ConcussionInjury, poisoning and procedural complications1/3720/1240/410/14
Most frequent other events
Showing 10 of 73
Most frequent other events
EventAR101 (Age 4-17)Placebo (Age 4-17)AR101 (Age 18-55)Placebo (Age 18-55)
Abdominal painGastrointestinal disorders194/37230/12418/416/14
DiarrhoeaGastrointestinal disorders61/37224/12413/417/14
NauseaGastrointestinal disorders146/37229/12420/413/14
NasopharyngitisInfections and infestations57/37220/1246/416/14
VomitingGastrointestinal disorders154/37230/1245/413/14
PruritusSkin and subcutaneous tissue disorders153/37234/12416/412/14
Abdominal pain upperGastrointestinal disorders152/37226/12416/414/14
CoughRespiratory, thoracic and mediastinal disorders152/37242/12412/413/14
Throat irritationRespiratory, thoracic and mediastinal disorders152/37234/12412/412/14
Oral pruritusGastrointestinal disorders151/37220/12415/414/14

Baseline characteristics

Measure Analysis Population Description: A total of 555 subjects were enrolled. However, only 551 subjects were included in the intent-to-treat (ITT) population. The ITT Population includes all subjects who received at least one dose of randomized study treatment.

Age, Customized
Age, Customized(Participants)AR101PlaceboTotal
Age customized categorical — Children (4-11 years)23889327
Age customized categorical — Adolescents (12-17 years)13435169
Age customized categorical — Adults (18-55 years)411455
Sex: Female, Male
Sex: Female, Male(Participants)AR101PlaceboTotal
Female18056236
Male23382315
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AR101PlaceboTotal
Hispanic or Latino301747
Not Hispanic or Latino383121504
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AR101PlaceboTotal
American Indian or Alaska Native101
Asian441054
Native Hawaiian or Other Pacific Islander101
Black or African American639
White329109438
More than one race000
Unknown or Not Reported321648
07

Study locations

69 sites
  • Banner University of Arizona Medical Center
    Tucson, Arizona 85724, United States
  • Arkansas Children's Hospital
    Little Rock, Arkansas 72202, United States
  • Long Beach Memorial Medical Center / Miller Children's and Women's Hospital
    Long Beach, California 90806, United States
  • UCLA Medical Center, Santa Monica
    Los Angeles, California 90404, United States
  • Allergy & Asthma Associates of Southern California dba Southern California Research
    Mission Viejo, California 92691, United States
  • Sean N. Parker Center for Allergy Research, LPCH at El Camino Hospital
    Mountain View, California 94040, United States
  • Peninsula Research Associates, Inc.
    Rolling Hills Estates, California 90274, United States
  • Allergy & Asthma Medical Group and Research Center, A.P.C
    San Diego, California 92123, United States
  • Rady Children's Hospital
    San Diego, California 92123, United States
  • University of California, San Francisco
    San Francisco, California 94158, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Colorado Allergy & Asthma Centers, P.C.
    Centennial, Colorado 80112, United States
  • National Jewish Health
    Denver, Colorado 80206, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010, United States
  • Windom Allergy, Asthma and Sinus
    Sarasota, Florida 34239, United States
  • University of South Florida Asthma, Allergy & Immunology Clinical Research Unit
    Tampa, Florida 33613, United States
  • Atlanta Allergy & Asthma Clinic, PA
    Marietta, Georgia 30060, United States
  • Idaho Allergy LLC dba Idaho Research
    Eagle, Idaho 83616, United States
  • Ann & Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • Comer Children's Hospital
    Chicago, Illinois 60637, United States
  • Sneeze, Wheeze & Itch Associates, LLC
    Normal, Illinois 61761, United States
  • IU North Riley Children's Specialists
    Carmel, Indiana 46032, United States
  • Chesapeake Clinical Research, Inc.
    Baltimore, Maryland 21236, United States
  • John Hopkins Hospital
    Baltimore, Maryland 21287, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • University of Michigan Health System
    Ann Arbor, Michigan 48109, United States
  • Clinical Research Institute Inc.
    Plymouth, Minnesota 55441, United States
  • Children's Mercy on Broadway
    Kansas City, Missouri 64111, United States
  • Asthma & Allergy Center, PC
    Bellevue, Nebraska 68123, United States
  • Atlantic Research Center, LLC
    Ocean City, New Jersey 07712, United States
  • Icahn School of Medicine at Mount Sinai, Clinical Research Unit
    New York, New York 10029, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • University of North Carolina at Chapel Hill, Clinical & Translational Research Center (CTRC)
    Chapel Hill, North Carolina 27599, United States
  • Clinical Research of Charlotte
    Charlotte, North Carolina 28277, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
  • Baker Allergy Asthma & Dermatology Research Center, LLC
    Portland, Oregon 97223, United States
  • Children's Hospital of Philadelphia: Allergy / Immunology
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • National Allergy and Asthma Research, LLC
    Charleston, South Carolina 29407, United States
  • LeBonheur Children's Hospital - Outpatient Building
    Memphis, Tennessee 38105, United States
  • Specially for Children Allergy, Asthma and Immunology Clinic
    Austin, Texas 78723, United States
  • Allergy Partners of North Texas Research
    Dallas, Texas 75230, United States
  • Children's Medical Center
    Dallas, Texas 75235, United States
  • Western Sky Medical Research
    El Paso, Texas 79903, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • Sylvana Research
    San Antonio, Texas 78229, United States
  • Virginia Mason Medical Center
    Seattle, Washington 98101, United States
  • Northwest Asthma and Allergy Center
    Seattle, Washington 98115, United States
  • Ohayon
    Hamilton, Ontario L8S 1G5, Canada
  • Cheema Research, Inc.
    Mississauga, Ontario L5A 3V4, Canada
  • Ottawa Allergy Research Corp
    Ottawa, Ontario K1G 6C6, Canada
  • Gordon Sussman Clinical Research, Inc.
    Toronto, Ontario M4V 1R2, Canada
  • Montreal Children's Hospital
    Montreal, Quebec H4A3J1, Canada
  • Odense Universitetshospital - Department of Dermatology and Allergy Center
    Odense, DK5000, Denmark
  • Charite Universitaetsmedizin Berlin
    Berlin, 13353, Germany
  • Medaimun GmbH
    Frankfurt am Main, 60596, Germany
  • Universitatsklinikum Frankfurt, Klinik fur Kinger und Jagendmedizin
    Frankfurt, 60590, Germany
  • Cork University Hospital
    Cork, Ireland
  • Az. Osp. - Univ. degli Studi- Padova, UOSD- Allergie Alimentari,
    Padova, 35128, Italy
  • Universitair medisch Centrum Groningen
    Groningen, 9713GZ, Netherlands
  • University Medical Center Groningen
    Groningen, 9713GZ, Netherlands
  • Hospital General Universitario Gregorio Maranon
    Madrid, 28007, Spain
  • Hospital Infantil Universitario Nino Jesus
    Madrid, 28009, Spain
  • Hospital Clinico San Carlos
    Madrid, 28040, Spain
  • Barnforskningscentrum, Sachs' Children and Youth Hospital
    Stockholm, 118 83, Sweden
  • Guy and St Thomas' NHS Foundation Trust
    London, SE1 7EH, United Kingdom
  • Central Manchester University Hospitals NHS Foundation Trust
    Manchester, M13 9WL, United Kingdom
  • University Hospital of South Manchester NHS Foundation Trust, Respiratory and Allergy Clinical Research Facility
    Manchester, M23 9LT, United Kingdom
08

References and documents

Publications

  • Nilsson C, Scurlock AM, Dellon ES, Brostoff JM, Pham T, Ryan R, Brown KR, Adelman DC, Aceves SS. Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4496-4501. doi: 10.1016/j.jaip.2021.07.048. Epub 2021 Aug 11. No abstract available. PubMed 34389504 ↗
  • Fernandez-Rivas M, Vereda A, Vickery BP, Sharma V, Nilsson C, Muraro A, Hourihane JO, DunnGalvin A, du Toit G, Blumchen K, Beyer K, Smith A, Ryan R, Adelman DC, Jones SM. Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy. Allergy. 2022 Mar;77(3):991-1003. doi: 10.1111/all.15027. Epub 2021 Sep 24. PubMed 34320250 ↗
  • PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, Beyer K, du Toit G, Hourihane JO, Jones SM, Shreffler WG, Marcantonio A, Zawadzki R, Sher L, Carr WW, Fineman S, Greos L, Rachid R, Ibanez MD, Tilles S, Assa'ad AH, Nilsson C, Rupp N, Welch MJ, Sussman G, Chinthrajah S, Blumchen K, Sher E, Spergel JM, Leickly FE, Zielen S, Wang J, Sanders GM, Wood RA, Cheema A, Bindslev-Jensen C, Leonard S, Kachru R, Johnston DT, Hampel FC Jr, Kim EH, Anagnostou A, Pongracic JA, Ben-Shoshan M, Sharma HP, Stillerman A, Windom HH, Yang WH, Muraro A, Zubeldia JM, Sharma V, Dorsey MJ, Chong HJ, Ohayon J, Bird JA, Carr TF, Siri D, Fernandez-Rivas M, Jeong DK, Fleischer DM, Lieberman JA, Dubois AEJ, Tsoumani M, Ciaccio CE, Portnoy JM, Mansfield LE, Fritz SB, Lanser BJ, Matz J, Oude Elberink HNG, Varshney P, Dilly SG, Adelman DC, Burks AW. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J Med. 2018 Nov 22;379(21):1991-2001. doi: 10.1056/NEJMoa1812856. Epub 2018 Nov 18. PubMed 30449234 ↗

Study documents

  • Study protocol · Jul 31, 2017
  • Statistical analysis plan · Jan 24, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02635776
Lead sponsor
Aimmune Therapeutics, Inc.
Responsible party
Sponsor
First posted
Dec 21, 2015
Start date
Dec 22, 2015
Primary completion
Dec 21, 2017
Completion
Jul 2, 2018
Results posted
Mar 17, 2022
Last update
Mar 17, 2022

Study contacts

Director of Regulatory Affairs
study chair · Aimmune Therapeutics, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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