Retrospective Kinetic Safety Evaluation of an Intravenous Micellar Excipient Platform

Retrospective, Multi-Center Observational Study Evaluating the Kinetic Safety and Tolerability of an Intravenous Micellar Excipient Platform in Clinical Practice

Protocol PICO-RWE-001: The goal of this observational study is to evaluate the kinetic safety and tolerability of an investigational intravenous micellar delivery platform. Researchers will abstract medical records of individuals who previously received this infusion in a clinical setting. The main questions the study aims to answer are: What adverse events (AEs) did participants experience during or after the infusion? Did participants discontinue their infusion regimen early due to adverse events? Researchers will abstract charts from clinical exposures occurring between June 1, 2025, and April 15, 2026. Participants do not undergo any new interventions or clinic visits.

Study Overview

• Status: Not yet recruiting
• Conditions: Infusion Reactions; Drug Related Side Effects and Adverse Reactions
• Intervention / Treatment: Drug: Legacy Heterogeneous Payload (Micellar Vehicle); Drug: PIV-850 (850-picometer Dual-NCE Acidic Matrix)

Detailed Description

Detailed Description: Protocol PICO-RWE-001 I. SCIENTIFIC RATIONALE AND PLATFORM ARCHITECTURE Protocol PICO-RWE-001 is a retrospective, multi-center observational clinical investigation designed to establish the systemic safety and tolerability profile of a proprietary sub-nanometer micellar delivery platform. The platform utilizes a specialized 850-picometer hydrophilic emulsion, engineered to encapsulate lipophilic organic compounds (PIV-850 and legacy heterogeneous payloads) for intravenous administration.

In biopharmaceutical development, particle size is a primary determinant of safety and biological fate. By operating at a sub-1nm scale, the Pico IV platform seeks to bypass the "Delivery Wall"-the biological and mechanical barriers that typically lead to embolic risk or infusion-related reactions (CARPA) when oil-in-water emulsions are administered systemically. This study aims to provide the irrefutable human safety data required to support a 505(b)(2) Investigational New Drug (IND) application and a subsequent petition for Phase 1 safety waivers.

II. METHODOLOGICAL ARCHITECTURE AND BIAS MITIGATION To ensure the highest tier of evidence for FDA CDER review and rigorous biostatistical evaluation, the study employs a rigorous Consecutive Selection Algorithm.

Sampling Integrity: Each of the maximum 25 activated clinical sites is mandated to abstract a minimum of 15 and a maximum of 25 unique patient records. Abstractors must identify every patient exposure administered within the eligibility window (June 1, 2025 - April 15, 2026) and work chronologically backward from the end date. This 100% consecutive sampling protocol is mathematically designed to eliminate selection bias.

CMC Standardization: Data abstraction is strictly limited to patient exposures utilizing single-use sterile vials. This ensures the safety signals collected perfectly mirror the Sponsor's intended commercial Chemistry, Manufacturing, and Controls (CMC) sterile fill-finish protocols, neutralizing multi-use cross-contamination variables.

III. CLINICAL STRATIFICATION AND KINETIC SAFETY

The study abstracts granular data to assess the "Excipient Kinetic Safety Margin." The data is stratified to evaluate the following variables:

Formulation Evolution: Safety profiles are compared between the legacy heterogeneous formulations and the purified PIV-850 isolate to identify any variance in tolerability linked to trace neutral byproducts or minor organic components.

Administration Velocity: The study analyzes safety outcomes between "IV Push" and "IV Drip" protocols. This allows the Sponsor to determine the relationship between systemic infusion rates and the incidence of transient infusion-related reactions.

Dose-Escalation Safety: Retrospective dosing data capturing extreme supratherapeutic exposures to provide a clinical view of the dose-response safety curve in a diverse, real-world population.

IV. SAFETY MONITORING PARAMETERS

The abstraction process focuses on identifying both systemic and localized adverse events (AEs). Specific clinical markers include:

Complement Activation-Related Pseudoallergy (CARPA): Monitoring for flushing, dyspnea, and tachycardia to validate the immunological "stealth" of the 850-picometer micelle.

Vehicle Toxicity: Evaluating renal and hepatic markers (where available in charts) and general systemic tolerability to confirm the safety of the Polysorbate 80-based vehicle load.

Longitudinal Tolerability: Assessing the rate of infusion regimen completion versus early discontinuation due to intolerance.

V. REGULATORY AND STRATEGIC RATIONALE By formalizing up to 625 human exposures into a structured, de-identified database, PICO IV is leveraging Real-World Evidence (RWE) to establish an Excipient Kinetic Safety Bridge. This study functions as the definitive safety foundation for a 505(b)(2) IND application, demonstrating that the sub-nanometer architecture is both safe and stable in a broad human population.

• Study Type: Observational
• Enrollment (Estimated): 625

Contacts and Locations

• Study Contact: Name: Joseph Young, Bachelor of Arts; Phone Number: 855-900-0020; Email: jyoung@picoiv.com
• Study Contact Backup: Name: Aimee Aquitania, Nurse Practitioner; Phone Number: 855-900-0020; Email: clinicals@picoiv.com

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95811
      • PICO IV Central Data Coordinating Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of a retrospective cohort of subjects who received (IV) infusions of the Sponsor's proprietary sub-nanometer micellar delivery platform (evaluating a legacy heterogeneous payload and the highly purified PIV-850 synthetic-equivalent dual-NCE matrix) within private medical clinics, specialty infusion centers, and outpatient practice settings across the United States.

The sample is drawn from a diverse clinical population evaluated between June 1, 2025, and April 15, 2026. To ensure high-fidelity safety data and eliminate selection bias, the population is derived via a mandatory 100% consecutive sampling algorithm at each activated site. This cohort represents subjects receiving investigational micellar infusions for a range of legacy clinical observations in routine medical practice, utilizing exclusively single-use sterile vials to ensure alignment with pharmaceutical-grade Chemistry, Manufacturing, and Controls (CMC) sterile fill-finish standards.

Description

Inclusion Criteria:

• Participant must have received at least one intravenous (IV) investigational exposure of the PICO IV 850-picometer micellar platform (evaluating either a legacy heterogeneous payload or the PIV-850 synthetic-equivalent dual-NCE matrix) between June 1, 2025, and April 15, 2026.
• The investigational product administered must have been drawn exclusively from a Single-Use Sterile Vial.
• The participant record must have been identified via a 100% consecutive sampling algorithm (15 to 25 patients per site) at the clinical site to eliminate selection bias.
• Electronic Medical Record (EMR) or clinic infusion logs must contain complete data regarding dosing, administration route (IV Push vs. IV Drip), and post-infusion safety observations.

Exclusion Criteria:

• Participants whose exposures were drawn from legacy multi-use vials.
• Participants with exposures occurring outside the specific date window of June 1, 2025 - April 15, 2026.
• Participants with incomplete clinical records where Infusion-Emergent Adverse Events (IEAEs) or safety outcomes were not documented.
• Participants whose records were not identified chronologically backward from April 15, 2026.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Legacy Payload (Micellar Vehicle); Participants who received intravenous infusions of the 850-picometer Polysorbate 80 micellar excipient vehicle carrying a legacy heterogeneous payload in a clinical setting between June 1, 2025, and April 15, 2026.	Drug: Legacy Heterogeneous Payload (Micellar Vehicle); A legacy iteration of the 850-picometer micellar delivery platform evaluating early kinetic safety thresholds. The Polysorbate 80 vehicle payload consisted of a broad heterogeneous precursor mixture. This formulation was administered intravenously (IV) via push or drip in clinical settings. Retrospective data abstracted from this cohort is utilized strictly to isolate the kinetic safety margin, thermodynamic stability, and tolerability of the delivery vehicle, entirely independent of the active payload.
PIV-850 Dual-NCE (Micellar Vehicle); Participants who received intravenous infusions of the 850-picometer Polysorbate 80 micellar excipient vehicle carrying the highly purified PIV-850 synthetic-equivalent dual-API NCE matrix in a clinical setting between June 1, 2025, and April 15, 2026.	Drug: PIV-850 (850-picometer Dual-NCE Acidic Matrix); An investigational, highly purified synthetic-equivalent New Chemical Entity (NCE) formulation comprising an acidic small-molecule complex, encapsulated in a proprietary 850-picometer hydrophilic micelle delivery system. Trace neutral byproducts generated during the thermal/ultrasonic manufacturing process are thermodynamically arrested within the micelle and classified strictly as inactive specified degradants (ICH Q3B limits). The formulation is engineered for intravenous (IV) administration via push or drip. This study observes the systemic safety, kinetic tolerability, and absence of Complement Activation-Related Pseudoallergy (CARPA) for this specific NCE profile in routine clinical practice.; Other Names: CORE-A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Infusion-Emergent Adverse Events (IEAEs)	Percentage of participants experiencing adverse events as documented in clinical charts. This includes specific monitoring for: 1) Infusion-Related Reactions: Complement Activation-Related Pseudoallergy (CARPA) symptoms such as facial flushing, dyspnea, tachycardia, or back/flank pain. 2) Vehicle Toxicity: Clinical signs of systemic intolerance to the Polysorbate 80-based micellar vehicle. Severity Grading: Events are systematically mapped and graded per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Grades 1-5).	From the initiation of the first intravenous infusion through 24 hours post-infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Early Infusion Discontinuation Due to Intolerance	The percentage of participants who discontinued their intended course of IV infusions specifically due to an adverse event or intolerance to the micellar formulation.	Duration of individual clinical exposure, up to 46 weeks.
Maximum Observed Dose Tolerability	Documentation of the highest dose tier (measured in total milligrams of active small-molecule payload) administered to participants without the occurrence of a severe adverse event. Retrospective abstraction will capture extreme supratherapeutic exposures (including multi-vial administrations exceeding the standard single-vial volume) to establish the maximum kinetic safety ceiling of the micellar delivery vehicle, providing a definitive safety margin for future prospective clinical targets.	Duration of individual clinical exposure, up to 46 weeks.

Collaborators and Investigators

• Sponsor: PICO IV, Inc.
• Investigators: Principal Investigator: Aimee Aquitania, Nurse Practitioner, Wellness Mobile Nursing SoCal Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): May 21, 2026
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immunomodulation; Real-World Evidence (RWE); Sub-nanometer delivery system; Micellar nanotechnology; 505(b)(2) Regulatory Pathway; Antimicrobial Resistance (AMR); Biofilm Disruption; Excipient Safety; Polysorbate 80
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: PICO-RWE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No