Primary: To describe safety and tolerability during longer-term administration of AR101 and follow-up observation after the last dose of AR101.Secondary: - To assess the level of desensitization achievable through extended maintenance dosing of…
ID
Source
Brief title
Condition
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are:
• Frequency of adverse events (AEs)
• Frequency of premature discontinuation of AR101 dosing due to AEs
• Frequency of premature discontinuation of dosing due to chronic/recurrent
gastrointestinal (GI) AEs
• Frequency of AEs that lead to a change in treatment regimen
• Frequency of AEs that lead to early withdrawal
• Frequency of anaphylaxis (as defined in Section 8.1.4.1)
• Frequency of use of epinephrine as a rescue medication
• Frequency of accidental/nonaccidental ingestion of peanut and other
allergenic foods
• Frequency of AEs following accidental/nonaccidental exposure to peanut and
other allergenic foods
• Frequency of eosinophilic esophagitis (EoE)
Secondary outcome
Secondary endpoints include:
• Proportion of subjects tolerating each challenge dose in the open-label food
challenge (OLFC) and the double-blind, placebo-controlled food challenge
(DBPCFC)
• The maximum tolerated challenge dose at each food challenge
• Change in tolerated dose of peanut protein
• Maximum severity of symptoms in each food challenge
• Frequency of use of epinephrine as a rescue medication during the food
challenges
• Change in peak expiratory flow (PEF)
• Change in Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT)
score
• Change in Total Nasal Symptom Score (TNSS)
• Changes in food allergy QoL scores as measured by Food Allergy Quality of
Life Questionnaires (FAQLQ), and the Food Allergy Independent Measure (FAIM)
questionnaire
• Change in Food Allergy Quality of Life - Parental Burden (FAQL-PB)
questionnaire score
Background summary
Peanut allergy is a common and serious condition that often affects children,
and is commonly associated with severe reactions, including life-threatening
anaphylaxis. Despite efforts at strict peanut avoidance, accidental exposure
continues to be a major concern in peanut allergy because allergic responses
can be triggered after ingestion of just milligram quantities of peanut
protein. Accidental exposures may result from commercial food products
mislabeling as well as inattention to, or mistrust of, food warning labels.
Oral immunotherapy for peanut allergy has been widely studied in recent years
and has demonstrated encouraging safety and efficacy results in early clinical
trials. In practical terms, this state of desensitization, in conjunction with
an avoidance diet, should be sufficient to protect a peanut-allergic individual
from the adverse effects of an accidental exposure to peanuts or
peanut-containing foods.
Study objective
Primary:
To describe safety and tolerability during longer-term administration of AR101
and follow-up observation after the last dose of AR101.
Secondary:
- To assess the level of desensitization achievable through extended
maintenance dosing of AR101
- To characterize the interaction of AR101 and asthma control or nasal allergy
symptoms in subjects with a history of asthma and/or allergic
rhinitis
- To evaluate subjects' quality of life (QoL) and treatment satisfaction during
AR101 treatment on daily and nondaily treatment regimens
- To evaluate parent/caregiver QoL during the child's treatment with AR101
Study design
ARC008 is a phase 3, international open-label, longer-term study of an AR101
CODIT regimen in children and adults with peanut allergy. Subjects entering
ARC008 will originate from an Aimmune AR101 clinical study or any future
clinical study that identifies ARC008 as a potential poststudy option in the
parent study protocol.
Because the dosing regimens and procedures in the parent studies are not
uniform, subjects will receive AR101 in1 of 5 treatment pathways in ACR008:
• Treatment Pathway 1 is for subjects who received and tolerated AR101 in a
daily or nondaily regimen in the parent study (except study ARC005). These
subjects will undergo a Screening/Baseline visit, and eligible subjects will
enter the Extended Maintenance Period. Subjects entering ARC008 on a dose > 300
mg QD will switch to 300 mg QD on the first day of the Extended Maintenance
Period. Subjects from parent study ARC004 on nondaily regimens who did not
tolerate 600 mg peanut protein (1043 mg peanut protein cumulative dose) at the
ARC004 Exit DBPCFC will switch to 300 mg QD on the first day of the Extended
Maintenance Period. Subjects receiving nondaily AR101 regimens in parent study
ARC004 who tolerated 600 mg peanut protein (1043 mg peanut protein cumulative
dose) at the ARC004 Exit DBPCFC will continue the nondaily AR101 regimen in the
Extended Maintenance Period.
• Treatment Pathway 2 is for the following subjects:
- Subjects who did not complete their AR101 dosing regimen (eg, up-dosing,
maintenance) in an eligible parent study (except study ARC005).
- Subjects from parent study ARC004, or any future clinical study identifying
ARC008 as a follow-on study, who received a nondaily AR101 dosing regimen and
who did not tolerate this regimen.
- Subjects from ARC004 who missed or withheld their nondaily AR101 dose for > 3
days, and subjects who received a nondaily AR101 dosing regimen and tolerated
less than the 300 mg single dose of peanut protein (443 mg cumulative) at the
ARC004 Exit DBPCFC, if continued treatment with AR101 was determined to be safe
per investigator judgment and after discussion with the medical monitor.
Subjects who did not complete their AR101 dosing regimen in an eligible parent
study will have a Screening/Baseline visit and continue the regimen in ARC008,
proceeding through the applicable study periods until the End of Treatment
visit. Subjects who enter ARC008 soon after completing the ARC004 Early
Discontinuation visit will have a Screening/Baseline visit, and eligible
subjects will start the Repeat Up-Dosing Period at a dose of 80, 120, or 160 mg
QD (a decrease in AR101 dose of approximately 50% to 75%) at the discretion of
the investigator. These subjects will then proceed sequentially through the
Initial Maintenance Period and Extended Maintenance Period. Subjects who
complete the Repeat Up-Dosing Period or who tolerate AR101 300 mg QD for 2
weeks in ARC004 will have a Screening/Baseline visit in ARC008 and then proceed
to the Initial Maintenance Period. Subjects who complete both the Repeat
Up-Dosing and Initial Maintenance Periods or receive AR101 300 mg QD for at
least 24 weeks in ARC004 will have a Screening/Baseline visit in ARC008 and
then proceed to the Extended Maintenance Period. In addition, ARC004 subjects
who tolerated the nondaily regimen in ARC004 but who subsequently do not
tolerate the nondaily regimen afterentering ARC008 Treatment Pathway 1 may
switch to Treatment Pathway 2 and start the Repeat Up-Dosing Period at
investigator discretion.
• Treatment Pathway 3 is for subjects who received placebo in the parent study
(except study ARC005). These subjects will undergo a Screening/Baseline visit,
and eligible subjects will start the Initial Escalation Period with a dose of
0.5 mg. Subjects will then proceed sequentially through the Up-Dosing Period,
Initial Maintenance Period, and Extended Maintenance Period.
• Treatment Pathway 4 is for subjects who received AR101 ands tolerated the
300mg/day dose for at least 2 consecutive weeks before the exit DBPCFC in
parent study ARC005. These subjects will have a Screening/Baseline visit, and
eligible subjects will start the Extended Maintenance Period.
• Treatment Pathway 5 is for subjects who received placebo in parent study
ARC005. These subjects will have a Screening/Baseline visit, and eligible
subjects will start the Initial Escalation Period at a dose of 0.5 mg.
Subjects will then proceed sequentially through the Up-Dosing Period, Initial
Maintenance Period, and Extended Maintenance Period.
Intervention
The investigational product is AR101 .
Doses are expressed as mg of peanut protein. For the lnitial Escalation and
Up-dosing periods, AR101 will be provided
in pull-apart capsules at doses of 0.5, 1.0, 10, 20, and 100 mg.
For the Initial Maintenance and Extended Maintenance periods, AR101 will be
provided in foil-lined sachets at a dose of 300 mg.
AR101 will be shipped directly to investigational sites and will be dispensed
according to subject identification number, using an interactive response
system. Trained investigational site personnel will administer AR101 directly
or dispense AR101 to the subject/guardian in a manner consistent with the
assigned dose level. AR101 is administered by QD dosing during lnitial
Escalation, Up-dosing, and Maintenance, and
by either QD, QOD, BlW, QW, or QOW dosing during EM.
Study burden and risks
Please Note: The number of visits per group / cohort varies. Please review
Protocol Appendix 1/2/3/4/5 page 131 -159 of the protocol.
Please Note: Screening/Baseline is conducted at the same time as the End of
Study Visit of the parent study.
- Blood draw: 5 times appr. 20 ml each time.
- number of visits: 14-24. lasting 2-4 hours.
- Physical Exam: 14-24 times
- questionnaires: 14-22 times
- skin prick test: 5-6 times
- Asthma test: up to 18 times
The above is for the first 3 years. If the subject is in the study longer than
3 years additional procedures will be performed every 3 months.
The side effects associated with AR101 are primarily allergic reactions. Most
subjects receiving AR101 experienced at least one side effect of allergic
reaction during the course of treatment. Symptoms included vomiting, abdominal
pain, nausea, cough, mouth and throat discomfort or pain, throat irritation,
hives, itching of the lips, lip swelling, lip blister, itchy tongue, runny
nose, sneezing, nasal congestion, wheezing, skin itching, eye itching, ear
itching, facial swelling, and fatigue.
Other common side effects experienced by 1% to 10% of subjects included
Diarrhoea / stomach irritation, Headache, Common cold or infection, Fever, Skin
problems (itching, rash, redness), Sleepiness / fatigue, Chest discomfort,
Anaphylaxis, Eosinophilic esophagitis,
Most of the side effects were mild to moderate and became less frequent over
time. Although the episodes of anaphylaxis were infrequent and
successfully managed, severe or life-threatening anaphylaxis is a potential
risk of AR101 . Also, whenever reoccurring
gastrointestinal symptoms occur with AR101 , there is a suspicion that EoE
might be present.
It is expected that the chance of having an allergic reaction is reduced when
the study drug is started at very small
doses, and when the dosing is increased slowly while being observed by the
Study Doctor.
There may be a risk that during study participation subjects may decrease their
vigilance against accidental peanut ingestion because they believe they are
protected from it. This phenomenon has been reported in previous trials.
Subjects (and partents/guardians) will be warned that they should continue to
practice their usual vigilance against accidental ingestion of peanuts or
peanut containing food.
Side Effects Associated with Food Challenges
Food challenges are expected to induce an allergic response in food-allergic
individuals. Allergic reactions can be severe, including life-threatening
allergic reactions; however, the risk of an allergic reaction is reduced by
beginning the challenge with a very small amount of the food, gradually
increasing the dose, and stopping the challenge at the first sign of a
significant reaction. ln case of an allergic reaction during the challenges,
medication will be administered (if needed) and the subject will be provided
with the standard care.
Side Effects Associated with Collecting Blood Samples
pain or bruising at the site where the blood will be drawn, fainting, swelling
of the vein, infection or bleeding at the puncture site.
Side Effects Associated with Skin Prick Test
minor pain or discomfort when the skin is pricked, A rash that spreads after
the application of the allergen, Widespread swelling and redness 6-24 hours
after the skin prick test. In rare cases, an anaphylactic reaction can occur.
Possible benifits:
-The study drug does not cure an allergy. However, it may lessen the body's
sensitivity or allergic response to the allergen, resulting in fewer symptoms.
-. lnformation from this study may help researchers to better understand peanut
allergy or to develop future tests or treatments to help patients with this
condition.
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Age
Inclusion criteria
A subject must meet all the following criteria to be eligible:
1. Prior participation in one of the following Aimmune AR101 clinical studies:
ARC002, ARC004, ARC005, ARC007, ARC010, ARC011, or any future clinical study of
that identifies ARC008 as a follow-on study option in the protocol
2. Written informed consent from the subject or guardian/parent (or both
parents where required by local authorities) in accordance with local
institutional review board (IRB)/ethics committee (EC) guidelines
3. Written assent from the subject as required by local IRB/EC guidelines
4. Use of effective birth control by sexually active females of childbearing
potential
Exclusion criteria
Subjects who meet any of the following criteria are not eligible:
1. Did not complete a minimum of 3 months of AR101 Maintenance in the parent
study if subject was assigned to AR101 in that study, except for subjects in
ARC004 who did not tolerate the nondaily AR101 dosing regimen, subjects in
ARC007 or ARC010, or unless specified otherwise in the parent study
2. 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, including malignancies
occurring within 5 years prior to Screening and clinically active autoimmune
diseases
3. Subjects with a history of alcohol, illicit or recreational drug or
prescribed medication abuse
4. Developed a clinically significant change in health status during the parent
study that, in the opinion of the investigator, would make the subject
unsuitable for participation in this study
5. Taking a prohibited medication, as listed in Section 5.9.5, except during
the follow-up observation period in this study
6. Currently participating in any other interventional clinical study other
than the Aimmune parent study, except during the follow-up observation period
in this study
7. Currently receiving or received within 5 years prior to Screening any type
of peanut or other food allergen immunotherapy, except AR101 or unless allowed
in the parent study, except during the follow-up observation period in this
study
8. Subject is living in the same household or is a dependent of sponsor
employees and/or site staff involved in conducting this study, except for
subjects originating from Aimmune Studies ARC002, ARC004, ARC007, ARC010, and
ARC011
9. Currently in the build-up phase of immunotherapy for any non-food allergen,
except during the follow-up observation period in this study
10. Hypersensitivity to epinephrine or hypersensitivity to any of the
excipients in the IP
11. Pregnant or breastfeeding
12. Inability to withhold antihistamines for 5 half-lives prior to the initial
day of escalation or visits at which an SPT or food challenge is conducted
13. Discontinued early from the parent study for any safety reason, except a
subject from study ARC004 who has experienced a lack of tolerance for a
nondaily dosing regimen, and subjects who discontinued early from an eligible
parent study due to AEs (including chronic or recurrent GI AEs) who require
continued safety follow-up only
14. Currently committed to an institution (eg, psychiatric institution, prison)
by virtue of an order issued by judicial or administrative
authorities.
15. Any other condition that, in the opinion of the investigator, precludes
participation for reasons of safety
16. Subjects unable to follow the protocol requirements
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001334-26-NL |
| ClinicalTrials.gov | NCT03292484 |
| CCMO | NL67207.042.18 |