This study is a Phase 1b/2a clinical trial to assess the safety, tolerability, and pharmacodynamics of multiple ascending doses (Escalation Phase) of CNP-201 with the goal of identifying a safe and tolerable dose level to be evaluated further in a larger number of subjects (Expansion Phase).
The Escalation Phase will consist of multiple cohorts (4 subjects per cohort) to identify a safe and tolerable dose(s). The Expansion Phase will consist of up to 40 additional subjects who will receive either a Placebo or CNP-201 at a safe and tolerable dose as determined from the Escalation Phase. One or more dose levels may be explored in the Expansion Phase. Subjects who meet all inclusion and no exclusion criteria at screening will be enrolled into the study. In the Escalation Phase, each cohort of four (4) subjects will receive CNP-201 by intravenous (IV) infusion on Days #1 and #8. Subjects in the Expansion Phase will be randomized in a 1:1 ratio to receive either a safe and tolerable dose level of CNP-201 identified in the Escalation Phase or Placebo (0.9% Sodium Chloride for injection). Subjects will remain in the clinic on Days #1 and #8 from the time of admission (prior to administration of CNP-201 or Placebo) through the final procedure conducted 4-hours post-dose that same day unless an infusion reaction, anaphylaxis, or other adverse event requires an extended duration of monitoring. Subjects will be discharged if safety parameters are acceptable to the investigator. Seven (7) days after the second administration of CNP-201 or Placebo, subjects must return to the clinic for collection of safety labs, PD measurements, and assessment of AEs and medication changes. Subjects will continue to be followed for safety, and tolerability during a 52-day Post-Dosing period. On Day 60, subjects will return to the clinic for collection of immune safety labs, PD measurements and to undergo Day 1 a Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) consisting of peanut and placebo (oat) challenges. On Day 61, subjects will return to the clinic to undergo Day 2 of the DBPCFC and final assessment of AEs and medication changes. The total duration of the study for an individual subject is approximately 67 days: 7 days for Screening; 8 days for CNP-201 or Placebo dosing; and 52 days post-dosing evaluation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
15
CNP-201 is comprised of purified peanut extract (PPE) drug substance dispersed within a negatively charged polymer matrix of poly (lactic-co-glycolic acid) (PLGA) particles at a target concentration of \~5 μg of PPE per mg of PLGA.
Placebo, (0.9% Sodium Chloride for IV infusion)
AllerVie Clinical Research
Birmingham, Alabama, United States
Long Beach Clinical Trials, LLC
Long Beach, California, United States
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Frequency tables will be presented by treatment group for all AEs and SAEs by System Organ Class (SOC) and Preferred Term (PT). Frequency tables will also be produced by treatment group for AEs leading to discontinuation from TP and study, by severity, and by causality. No formal statistical testing will be done.
Time frame: through Study Completion, an average of 67 Days
Serum Cytokines (TNF-α, IL-2, IL-6, IL-8, IL-1β, MCP-1, MIP-1β, MIP-1α, IFN-γ, and IL-12p70)
Summary statistics will be presented for the change from baseline values for Serum Cytokines (TNF-α, IL-2, IL-6, IL-8, IL-1β, MCP-1, MIP-1β, MIP-1α, IFN-γ, and IL-12p70)
Time frame: Baseline (Day 1 pre-dose) through Day 60, an average of 52 Days
Change in the ratio of peanut specific IgE to IgG
The mean change in the ratio of peanut specific IgE to IgG as measured by ImmunoCap assay from Baseline (Screening) to Visit 5 within CNP-201 and Placebo treatment groups will be analyzed
Time frame: Baseline (Day 1 pre-dose) through Day 60, an average of 52 Days
Change in peanut specific IgE between CNP-201 and Placebo
The mean change of peanut specific IgE to IgG as measured by ImmunoCap assay from Baseline (Screening) to Visit 5 within CNP-201 and Placebo treatment groups will be analyzed
Time frame: Baseline (Day 1 pre-dose) through Day 60, an average of 52 Days
Difference in percentage of subjects who pass a DBPCFC
Difference in percentage of subjects who pass a DBPCFC (do not reach an eliciting dose at or before the 2000 mg dose level, 4043 mg cumulative) between placebo and CNP-201 at Day 60 and at Day 180
Time frame: At Day 60
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Southern California Research
Mission Viejo, California, United States
Allergy & Asthma Medicaal Group and Research Center
San Diego, California, United States
Rush University Medical Center
Chicago, Illinois, United States
Sneeze, Wheeze and Itch Associates, LLC
Normal, Illinois, United States
Meridian Clinical Research. LLC
Overland Park, Kansas, United States
Institute for Asthma & Allergy
Chevy Chase, Maryland, United States
Aventiv Research, Inc
Columbus, Ohio, United States
Vital Prospects Clinica Research Institute
Tulsa, Oklahoma, United States
...and 7 more locations
Change in the proportion of peanut specific Th2a+ T cells
Change in the proportion of peanut specific Th2a+ T cells (peanut specific Th2a+ cells / total peanut specific T cells) following ex vivo stimulation of PBMCs between placebo and CNP-201 at baseline and at Day 15
Time frame: Baseline (Day 1 pre-dose) through Day 15, an average of 15 Days
Change in the effective concentration at 50% of maximal basophil activation (EC50)
Change in the effective concentration at 50% of maximal basophil activation (EC50) as measured by a Basophil Activation Test (CD203c+/CD63+/- basophil activation) between placebo and CNP-201 at baseline and at Day 60 and at Day 180
Time frame: Baseline (Day 1 pre-dose), at Day 15, and at Day 60
Change in the proportion of peanut specific T regulatory cells (peanut specific T regulatory cells / peanut specific CD4+ effector memory cells)
Change in the proportion of peanut specific T regulatory cells (peanut specific T regulatory cells / peanut specific CD4+ effector memory cells) following ex vivo stimulation of PBMCs between placebo and CNP 201 at baseline and at Day 15
Time frame: Baseline (Day 1 pre-dose) and at Day 15