CNP-201 in Subjects With Peanut Allergy
Study Details
Study Description
Brief Summary
This study is a Phase 1b/2a randomized, double-blind, placebo-controlled 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Subjects who meet all inclusion and no exclusion criteria at screening will be enrolled into the study. Subjects will be randomized on Day 1 in a 2:1 ratio to receive either CNP-201 or Placebo (0.9% Sodium Chloride USP) by intravenous (IV) infusion. Subjects will be administered CNP-201 or Placebo on Day 1 and on Day 8.
Subjects will remain in the clinic on Day 1 and Day 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 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 the 52-day Post-Dosing period. Subjects will return to the clinic on Day 38 for collection of immune safety labs and PD measurements.
On Day 60, subjects will return to the clinic for collection of immune safety labs, PD measurements and to undergo a Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) consisting of peanut and placebo (oat) challenges. The DBPCFC will be conducted with a study physician or staff trained to manage clinical emergencies present on site, with immediate access to emergency medications and equipment, and within close proximity to hospital emergency departments for rapid delivery of urgent care if needed.
An additional 120-day Post-Dosing period is optional. On Day 90 and Day 120, subjects may choose to return to the clinic for collection of immune safety labs, and PD measurements. Subjects may then return to the clinic for the end of study visit on Day 180 for a second DBPCFC consisting of peanut and placebo (oat) challenges, collection of safety labs, PD measurements, and final assessment of AEs and medication changes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CNP-201 25 mg 200 mL intravenous infusion on Day 1 and Day 8: 25 mg CNP-201 |
Drug: CNP-201
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.
|
| Experimental: CNP-201 TBD(1) mg 200 mL intravenous infusion on Day 1 and Day 8: TBD mg CNP-201 |
Drug: CNP-201
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.
|
| Experimental: CNP-201 TBD(2) mg 200 mL intravenous infusion on Day 1 and Day 8: TBD mg CNP-201 |
Drug: CNP-201
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 Comparator: Placebo 200 ml intravenous infusion on Day 1 and Day 8: CNP-201 Placebo |
Drug: Placebo
CNP-201 Placebo
|
Outcome Measures
Primary Outcome Measures
- Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) [through Study Completion, an average of 180 Days]
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.
- Serum Cytokines (TNF-α, IL-2, IL-6, IL-8, IL-1β, MCP-1, MIP-1β, MIP-1α, IFN-γ, and IL-12p70) [Baseline (Day 1 pre-dose) through Study Completion, an average of 180 Days]
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)
Secondary Outcome Measures
- Change in the ratio of peanut specific IgE to IgG [Baseline (Day 1 pre-dose) through Visit 5, an average of 38 Days]
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
- Change in peanut specific IgE between CNP-201 and Placebo [Baseline (Day 1 pre-dose) through Visit 5, an average of 38 Days]
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
- Difference in percentage of subjects who pass a DBPCFC [Between Day 60 and Day 180]
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
- Change in the proportion of peanut specific Th2a+ T cells [Baseline (Day 1 pre-dose) through Visit 4, an average of 15 Days]
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
- Change in the effective concentration at 50% of maximal basophil activation (EC50) [Baseline (Day 1 pre-dose) through Visit 6a, an average of 60 Days and Visit 9a, an average of 180 Days]
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
- Change in the proportion of peanut specific T regulatory cells (peanut specific T regulatory cells / peanut specific CD4+ effector memory cells) [Baseline (Day 1 pre-dose) through Visit 4, an average of 15 Days]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men and non-pregnant women, ages 16 to 55 years inclusive.
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Subjects with physician-diagnosed peanut allergy or documented history of peanut allergy. Note: If subject does not have documented history in their medical record but is reasonably suspected of having peanut allergy and is deemed to otherwise be a good candidate for this trial, the screen testing (peanut specific IgE, SPT, etc.) may be used to establish the peanut allergy and the PI may subsequently document the peanut allergy to fulfil this inclusion criterion.
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Subjects with weight ≥ 31.25 kg at Screening. Subjects who fall outside of this range may be included at the discretion of the investigator.
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Subjects with a documented history of non-severe anaphylaxis (Grade ≤ 3) to peanuts, including mild wheezing or dyspnea without hypoxia.
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Subjects with peanut specific IgE > 5 kU/L as measured by ImmunoCAP at Screening. Subjects who have previously been on OIT for peanut allergy and who do not have peanut specific IgE ≥ 5 kU/L as measured by ImmunoCAP at Screening may be included at the discretion of the investigator, OR Subjects with a positive skin prick test (SPT) to peanut with a change in wheal diameter ≥ 3 mm as compared to a negative control (50% glycerin) at Screening. Subjects who have previously been on OIT for peanut allergy and who do not have a positive skin prick test (SPT) to peanut with a change in wheal diameter ≥ 3 mm at Screening may be included at the discretion of the investigator.
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Subjects who are self-reported to be on a peanut free diet with no suspected peanut exposure, including any peanut food challenge, for at least 14 days prior to Screening and agreement to continue restriction to peanut exposure during the study.
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Female subjects and male subjects and their female spouse/partners who are willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods, intrauterine device (IUD), or use of spermicide combined with a barrier method (e.g., condom, diaphragm) starting at Screening and continuing to Day
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Female subjects who agree to not breastfeed starting at initial Screening and continuing to Day 38.
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Female subjects who agree to not donate ova starting at initial Screening and continuing to Day 38..
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Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent.
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Subjects who are willing to perform and comply with all study procedures.
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Male subjects who agree to not donate sperm starting at Screening and continuing to Day 38.
Exclusion Criteria:
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Subjects with history of severe anaphylaxis to peanuts defined as neurological compromise or requiring intubation.
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Subjects who have received administration of vaccinations in the following timeframe:
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Any live vaccine (other than intranasal Influenza) within 28 days prior to Screening.
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Any subunit vaccine within 14 days prior to Screening.
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Any COVID-19 vaccine within 14 days prior to Screening. Subjects who have received the first dose of any COVID-19 vaccine may not screen for the study until 14 days following their last dose of the vaccine if applicable.
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Any planned vaccination prior to Day 15.
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Subjects in build-up phase of immunotherapy for aeroallergens or venom. Individuals tolerating maintenance aeroallergen or venom immunotherapy at Screening can be enrolled.
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Subjects with relative contraindication or inability to use epinephrine auto-injector.
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Subjects who have used the following drug(s) within 2 months prior to Screening:
Systemic steroids, chemical mediator-isolation inhibitors, Th2 cytokine inhibitors, thromboxane -blockers, angiotensin-converting enzyme inhibitors, and/or angiotensin-receptor blockers unless, in the investigator's opinion, the underlying condition being treated by the drug is well controlled and the drug dose and frequency is not expected to interfere with the mechanism of action of CNP-201 as determined in consultation with the sponsor.
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Subjects who have used biologics and/or immune modulators (including but not limited to anti-TNFα antibody and anti-IgE monoclonal antibody) within three months prior to Screening.
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Subjects with a history of allergic reactions such as anaphylactic shock, angioedema with airway constriction, or hypotension caused by food other than peanut and/or medical products.
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Subjects with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/ antibody as determined at Screening.
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Subjects who are immunocompromised, including those receiving immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily or on alternate days for 2 weeks or more within 6 months prior to Screening, any dose of corticosteroids within 30 days of Screening, or high dose inhaled corticosteroids [> 960 μg/day of beclomethasone dipropionate or equivalent]) or other immunosuppressive agents.
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Subjects with a history of unstable angina pectoris, cardiac disease or dysrhythmias, severe chronic lung disease, or any other chronic medical condition that which in the opinion of the investigator, would pose a significant health threat in the event of anaphylaxis/treatment of anaphylaxis.
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Subjects with active eosinophilic esophagitis (EoE) or other eosinophilic gastrointestinal disease.
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Subjects with clinically significant abnormality on electrocardiogram (ECG) at Screening that, in the investigator's opinion, makes the subject unsuitable for study participation.
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Subjects with active malignancy, or history of malignancy or chemotherapy within the past 5 years other than history of localized or surgical removal of focal skin cancer, or cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy.
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Subjects with a mental condition such as schizophrenia, bipolar disorder, major depressive disorder, generalized anxiety disorder, panic disorder/attacks, or subjects who have received drug(s) for the treatment of dementia.
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Subjects with severe or poorly controlled (resistant to appropriate medical intervention) atopic disease including atopic dermatitis, generalized eczema, allergic rhinitis and/or urticaria.
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Subjects who use beta-agonists (within 12 hours), theophylline (within 12 hours), and cromolyn (within 12 hours) prior to SPTs.
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Subjects with severe or uncontrolled/difficult to control asthma/wheezing, defined by at least one of the following criteria:
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Global Initiative for Asthma (GINA) 2020: Personalized management to control symptoms and minimize future risk requiring treatment Steps 4 or 5 (Appendix 3) OR;
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Forced expiratory volume in 1 second (FEV1) < 80% of predicted, or ratio of FEV1 to forced vital capacity (FEV1/FVC) < 75% of predicted, with or without controller medications (only those able to reliable perform spirometry. If unable to do spirometry, PEF of > 80% is acceptable OR;
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One overnight admission to a hospital in the past year for asthma OR;
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Emergency room visit for asthma within 6 months prior to Screening OR;
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History of two or more systemic corticosteroid courses within 6 months of Screening or one course of systemic corticosteroids within 3 months of Screening to treat asthma/wheezing OR;
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Prior intubation/mechanical ventilation for asthma/wheezing.
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Subjects who have received an investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to Screening.
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Subjects with any condition which, in the investigator's opinion, makes the subject unsuitable for study participation: Past or current medical problems, history of other chronic diseases requiring therapy, findings from physical assessment, or abnormalities in clinical laboratory testing that are not listed above, which in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
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Subjects with a known sensitivity to any components of CNP-201 (PLGA, sucrose, mannitol, or sodium citrate).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AllerVie Clinical Research | Birmingham | Alabama | United States | 35209 |
| 2 | Long Beach Clinical Trials, LLC | Long Beach | California | United States | 90806 |
| 3 | Southern California Research | Mission Viejo | California | United States | 92691 |
| 4 | Allergy & Asthma Medicaal Group and Research Center | San Diego | California | United States | 60062 |
| 5 | Children's Research Institute | Washington | District of Columbia | United States | 20010 |
| 6 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 7 | Sneeze, Wheeze and Itch Associates, LLC | Normal | Illinois | United States | 61761 |
| 8 | Meridian Clinical Research. LLC | Overland Park | Kansas | United States | 66210 |
| 9 | Aventiv Research, Inc | Columbus | Ohio | United States | 43213 |
| 10 | Vital Prospects Clinica Research Institute | Tulsa | Oklahoma | United States | 74136 |
| 11 | National Allergy and Asthma Research, LLC | North Charleston | South Carolina | United States | 29420 |
| 12 | Allergy Partners of North Texas Research | Dallas | Texas | United States | 75230 |
| 13 | Pharmaceutical Research & Consulting, Inc | Dallas | Texas | United States | 75231 |
| 14 | Western Sky Medical Research | El Paso | Texas | United States | 79903 |
| 15 | Tranquil Clinical and Research Consulting Services | Houston | Texas | United States | 77598 |
| 16 | Clinical Research Partners | Richmond | Virginia | United States | 23226 |
| 17 | Seattle Allergy & Asthma Research Institute | Seattle | Washington | United States | 98115 |
Sponsors and Collaborators
- COUR Pharmaceutical Development Company, Inc.
Investigators
- Study Director: Greta Wodarcyk, PhD, COUR Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CNP-201-5.002