Trial Outcomes & Findings for Tolerance Following Peanut Oral Immunotherapy (NCT NCT01750879)
NCT ID: NCT01750879
Last Updated: 2021-07-28
Results Overview
1. Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms. 2. Partial Tolerance: ED at DBPCFC3 \<4430 mg but =\>430 mg AND \>10-fold more than at DBPCFC1. 3. Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1. 4. Treatment Failure - withdrawal
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
41 participants
Primary outcome timeframe
Average 515 days from DBPCFC1 to DBPCFC3
Results posted on
2021-07-28
Participant Flow
Participants recruited from a specialty clinic, college campus clinic, and community outreach (including advertisements on Boston MBTA) between May 2013 and January 2016. The first participant was enrolled in August 2013.
113 screened, 72 excluded (3 Lost to follow-up pre-randomization; 8 Re-screened following protocol change; 21 Screen Fail no objective symptoms on DBPCF1; 29 Screen Fail prior to DBPCFC; and 11 Voluntary withdrawal pre-randomization)
Participant milestones
| Measure |
Peanut Flour
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo (Oat) Flour
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
11
|
|
Overall Study
DBPCFC2
|
20
|
8
|
|
Overall Study
DBPCFC3
|
20
|
0
|
|
Overall Study
COMPLETED
|
20
|
8
|
|
Overall Study
NOT COMPLETED
|
10
|
3
|
Reasons for withdrawal
| Measure |
Peanut Flour
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo (Oat) Flour
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
|---|---|---|
|
Overall Study
Adverse Event
|
8
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Did not complete per protocol
|
0
|
3
|
Baseline Characteristics
Tolerance Following Peanut Oral Immunotherapy
Baseline characteristics by cohort
| Measure |
Active
n=30 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=11 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
14 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
20.5 Years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
16.3 Years
STANDARD_DEVIATION 7.2 • n=7 Participants
|
19.4 Years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
18 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Transgender
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
11 participants
n=7 Participants
|
41 participants
n=5 Participants
|
|
Peanut-specific IgE
|
116 kU/L
STANDARD_DEVIATION 156 • n=5 Participants
|
97.5 kU/L
STANDARD_DEVIATION 121 • n=7 Participants
|
111.3 kU/L
STANDARD_DEVIATION 146.4 • n=5 Participants
|
PRIMARY outcome
Timeframe: Average 515 days from DBPCFC1 to DBPCFC31. Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms. 2. Partial Tolerance: ED at DBPCFC3 \<4430 mg but =\>430 mg AND \>10-fold more than at DBPCFC1. 3. Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1. 4. Treatment Failure - withdrawal
Outcome measures
| Measure |
Active
n=30 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=11 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Tolerance, Partial Tolerance, or Treatment Failure
Tolerance
|
5 Participants
|
0 Participants
|
—
|
—
|
|
Tolerance, Partial Tolerance, or Treatment Failure
Partial Tolerance
|
8 Participants
|
0 Participants
|
—
|
—
|
|
Tolerance, Partial Tolerance, or Treatment Failure
Treatment Failure- non-desensitized
|
7 Participants
|
8 Participants
|
—
|
—
|
|
Tolerance, Partial Tolerance, or Treatment Failure
Treatment Failure- withdrawal
|
10 Participants
|
3 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 630 daysPopulation: Per protocol, subjects were unblinded after DBPCFC2 and those on placebo were not subjected to DBPCFC3
The change in median eliciting dose (ED) from DBPCFC1 to DBPCFC3. (note: ED right censored to maximum dose for those without any clinical reactivity)
Outcome measures
| Measure |
Active
n=20 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Clinical: Tolerance
|
4000 mg
Interval -403.0 to 4400.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 518 daysPopulation: 30 active and 11 placebo had baseline challenge (DBPCFC1); 20 active and 8 placebo had first post-treatment challenge (DBPCFC2). Change in median eliciting dose restricted to the 20 and 8 who competed DBPCFC2 (i.e., per protocol)
\- The change in median eliciting dose (ED) from DBPCFC1 to DBPCFC2.
Outcome measures
| Measure |
Active
n=20 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=8 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Clinical: Desensitization
|
4000 mg
Interval -3.0 to 4400.0
|
-65 mg
Interval -430.0 to 500.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 630 days\- The rate of reported adverse advents due to accidental ingestions in the active versus placebo groups.
Outcome measures
| Measure |
Active
n=30 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=11 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Clinical: Safety
|
0 Participants
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 630 daysPopulation: We conducted a nested case-control analysis of a subset of actively treated (by treatment outcome) versus placebo treated patients. Genomic DNA was used to amplify and sequence the complementarity-determining region 3 (CDR3) regions (immunoSEQ assay; Adaptive Biotechnologies). Enriched clonotypes in the CD154+ fraction (doi: https://doi.org/10.1101/2020.05.11.088286) were analyzed for differences by Rank Abundance Curve analysis (R package alakazam; Chao A, et al. Ecology. 2015 96, 11891201).
The change in the TCR clonal diversity of in vitro allergen-expanded Treg cells and induced Treg cells measured by TCRB CDR3 sequence clonotyping of sorted cells during active treatment among participants who achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined in clinical endpoints) versus the Treatment Failure Group. We conducted a nested case-control analysis of a subset of actively treated (by treatment outcome) versus placebo treated patients. Genomic DNA was used to amplify and sequence the complementarity-determining region 3 (CDR3) regions (immunoSEQ assay; Adaptive Biotechnologies). Enriched clonotypes in the CD154+ fraction (doi: https://doi.org/10.1101/2020.05.11.088286) were analyzed for differences by Rank Abundance Curve analysis (R package alakazam; Chao A, et al. Ecology. 2015 96, 11891201) to determine differences in clonal diversity.
Outcome measures
| Measure |
Active
n=5 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=6 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
n=6 Participants
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
n=5 Participants
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Mechanistic: TCR Clonal Diversity
|
0.010499258 percentage of clones
Interval 0.0061792665 to 0.014819249
|
0.003841910 percentage of clones
Interval 0.0011267402 to 0.00655708
|
0.003090797 percentage of clones
Interval 0.0007072315 to 0.005474362
|
0.003592776 percentage of clones
Interval 0.0009671402 to 0.006218412
|
SECONDARY outcome
Timeframe: 518 daysPopulation: skin test quality was poor
The change in eliciting dose of end-point dilution skin testing between actively treated and placebo treated participants following maintenance therapy and the change in ED of end-point dilution skin testing among actively treated participants following maintenance therapy and avoidance between clinical outcome groups.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 630 daysPopulation: basophil time points inadequate for analysis
The change in peanut-specific basophil ED in actively treated participants at the end of maintenance and the end of avoidance between clinical outcome groups.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 518 daysThe change in peanut allergen-specific IgG4 in actively treated participants by the end of maintenance between clinical outcome groups.
Outcome measures
| Measure |
Active
n=22 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=9 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Mechanistic: Change in Peanut Allergen-specific IgG4
|
0.664 mg/mL
Standard Deviation 0.559
|
0.375 mg/mL
Standard Deviation 0.247
|
—
|
—
|
SECONDARY outcome
Timeframe: 630 daysPopulation: Subjects as defined per protocol. All 5 placebo were 'treatment failure -- non-desensitized' and per protocol, none were eligible for avoidance or DBPCFC3. Total RNA from CD154+ and CD154-CD69- T cells was used for cDNA synthesis and amplification. Read depth of approximately 30 million per sample (Illumina HiSeq) and aligned to the hg19 human reference genome with the ensemble version 75 annotation. Differential expression analysis was performed using DESeq2 v 1.30.1 (R v 4.04).
Statistically significant gene expression changes (as number of genes) by transcriptional profiling of regulatory and effector T cell populations before and after OIT between clinical outcome groups. Total RNA from CD154+ and CD154-CD69- T cells was used for cDNA synthesis and amplification. Libraries were prepared and sequenced to a read depth of approximately 30 million reads per sample (Illumina HiSeq) and aligned to the hg19 human reference genome with the ensemble version 75 annotation using STAR version 2.5.3a,(Dobin et al. Bioinformatics 2013) and gene expression was summarized using RSEM version 1.3.0 (Li et al. BMC Bioinform 2013). Differential expression analysis was performed using DESeq2 v 1.30.1 (R v 4.04). Significance level was set at an unadjusted P value less than .001.
Outcome measures
| Measure |
Active
n=5 Participants
Participants will be randomly assigned by study statistician to treatment or placebo groups at a ratio of 3:1 following a double-blind placebo controlled food challenge, DBPCFC1, on 2 separate days. One challenge will consist of 5 doses of peanut in increasing amounts up to a total of 443 mg of peanut protein masked in vehicle food. The second day will consist of placebo material given similarly. Participants with an eliciting dose of 443mg or less will receive daily escalating dosages of peanut flour OIT in a blinded fashion, as described in the modified rush phase, until a daily dose of 4000 mg is reached. Following treatment, a 2nd challenge will occur DBPCFC2, identical to DBPCFC1, but with additional doses of 1000 mg and 3000 mg for a cumulative dose of 4443 mg peanut protein. After 12 weeks of complete peanut avoidance, participants will undergo a third challenge, DBPCFC3, which will follow a slightly different schedule of doses for a cumulative dose of 4430 mg peanut protein.
|
Placebo
n=6 Participants
Participants in the placebo arm will follow the same protocol except they receive daily escalating dosages of placebo oat flour, and they will not participate in DBPCFC3. Following DBPCFC2, assignment will be unblinded and placebo participants will be offered open-label active treatment under a separate protocol.
|
Peanut Flour -- Treatment Failure
n=6 Participants
Treatment Failure: Inability to tolerate the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1
|
Placebo
n=5 Participants
Placebo (Oat Flour) treated participants.
|
|---|---|---|---|---|
|
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
genes up at maintenance versus baseline
|
86 number of differentially expressed genes
|
45 number of differentially expressed genes
|
12 number of differentially expressed genes
|
9 number of differentially expressed genes
|
|
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
genes up at avoidance versus baseline
|
42 number of differentially expressed genes
|
14 number of differentially expressed genes
|
43 number of differentially expressed genes
|
NA number of differentially expressed genes
not evaluable per protocol
|
|
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
genes down at maintenance versus baseline
|
43 number of differentially expressed genes
|
154 number of differentially expressed genes
|
18 number of differentially expressed genes
|
3 number of differentially expressed genes
|
|
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
genes down at avoidance versus baseline
|
9 number of differentially expressed genes
|
39 number of differentially expressed genes
|
15 number of differentially expressed genes
|
NA number of differentially expressed genes
not evaluable per protocol
|
Adverse Events
Peanut Flour
Serious events: 1 serious events
Other events: 30 other events
Deaths: 0 deaths
Oat Flour
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Peanut Flour
n=30 participants at risk
Oral Immunotherapy with peanut flour.
Peanut Flour: Peanut Flour
|
Oat Flour
n=11 participants at risk
Oral Immunotherapy with oat flour.
Oat Flour: Oat Flour
|
|---|---|---|
|
Psychiatric disorders
Suicidal Ideation, unrelated
|
3.3%
1/30 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/11 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
Other adverse events
| Measure |
Peanut Flour
n=30 participants at risk
Oral Immunotherapy with peanut flour.
Peanut Flour: Peanut Flour
|
Oat Flour
n=11 participants at risk
Oral Immunotherapy with oat flour.
Oat Flour: Oat Flour
|
|---|---|---|
|
Immune system disorders
Anaphylactic Reaction
|
35.0%
7/20 • Number of events 7 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
77.8%
7/9 • Number of events 7 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Gastrointestinal disorders
Abdominal Pain
|
5.0%
1/20 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
11.1%
1/9 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Gastrointestinal disorders
Nausea/Vomting
|
3.3%
1/30 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/11 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.3%
1/30 • Number of events 2 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/11 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
0.00%
0/20 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
11.1%
1/9 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Respiratory, thoracic and mediastinal disorders
Asthma Exacerbation
|
3.3%
1/30 • Number of events 2 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/11 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Immune system disorders
Skin/oral pruritis
|
5.0%
1/20 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
22.2%
2/9 • Number of events 2 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Skin and subcutaneous tissue disorders
Angiodema
|
5.0%
1/20 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/9 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Gastrointestinal disorders
Reflux
|
5.0%
1/20 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
0.00%
0/9 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Gastrointestinal disorders
Other
|
0.00%
0/20 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
11.1%
1/9 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
|
Respiratory, thoracic and mediastinal disorders
Wheeze/SOB
|
0.00%
0/20 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
11.1%
1/9 • Number of events 1 • August 2013 to January 2016 (2 years and 5 months)
Build up AEs, At home AEs, DBPCFC2 AEs
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place