OPT101 in Patients With Community Acquired Pneumonia (CAP) With Sepsis

A Phase 1b Study to Assess the Safety, Tolerability and Pharmacokinetics of OPT101 in Patients With Community Acquired Pneumonia (CAP) With Sepsis

OPT101-100-40 is a multicenter, randomized, placebo-controlled, multiple-ascending-dose, sequential-group, investigator- and participant-blinded, sponsor-unblinded, study of OPT101 vs placebo when administered for up to 4 days to patients admitted to the hospital for treatment of Community Acquired Pneumonia (CAP) with sepsis.

This study will be performed in patients with Community Acquired Pneumonia (CAP) with Sepsis, who are 18 years or older to evaluate the safety and tolerability of OPT101 in a population with elevated levels of pathologic CD40.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Community Acquired Pneumonia (CAP)
• Intervention / Treatment: Other: Placebo; Drug: OPT101

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lisa M Boswell, MS; Phone Number: 720-315-0198; Email: lmboswell@live.com
• Study Contact Backup: Name: Marc L Giles, BS; Phone Number: 720-315-0198; Email: mg@op-t.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health and Hospital Authority
      • Principal Investigator: Ivor S Douglas, MD
      • Contact: Terra Miller, MSN, RN; Phone Number: 303-602-1438; Email: Terra.Hiller@dhha.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Are able and willing to give signed informed consent (legally authorized representative can provide informed consent if needed).
2. ≥18 years old;

3. Patients hospitalized for clinically suspected community acquired pneumonia (CAP), defined as the occurrence of (within 48h from hospital admission) at least 1 of the following signs:

   • respiratory rate > 30 breaths/min;
   • fever (> 38.0°C or > 100.4° F);
   • leukopenia (≤ 4,000 WBC/mm3 or leukocytosis (≥ 12,000 WBC/mm3);
   • adults ≥ 70 years of age; altered mental status with no other recognized cause;

   AND at least 1 of the following:

   • New onset of purulent sputum or change in character of sputum or increased respiratory secretions;
   • New onset or worsening cough, or dyspnea, or tachypnea;
   • Rales or bronchial breath sounds; AND Radiologic imaging (chest x-ray or CT scan) evidence of pulmonary involvement with new and persistent or progressive and persistent infiltrate, consolidation or cavitation AND SpO2 <92% at room air, or PaO2/FiO2 (or SpO2/FiO2) <300; recorded on one episode
4. Need for non-invasive supplemental oxygen (nasal cannula, simple mask, venturi or reservoir cannula/mask or heated high flow nasal cannula oxygen.

5. Females of child-bearing potential who are sexually active must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:

   • Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after the last OPT101 dose
   • A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after the last OPT101 dose
   • A male sexual partner who agrees to use a male condom with spermicide
   • A sterile sexual partner

Exclusion Criteria:

1. Need for endotracheal intubation and mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at time of study screening
2. QTc ≥ 450 msec on screening ECG
3. Hepatic dysfunction: ALT or AST > 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score ≥ 12)
4. Recent or active hepatitis A infection; test positive or have been treated for hepatitis B, hepatitis C, or HIV infection; evidence of active or untreated latent TB; a recent history of recurrent herpes zoster and/or opportunistic infection; and/or taking immunosuppressant medication.
5. Renal dysfunction: estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2, or need for hemodialysis or hemofiltration
6. Current use of >2 immunosuppressive medications or immunosuppression status (AIDS, aplastic anemia, asplenia, systemic chemotherapy within the past 3 months, neutropenia (ANC < local LLN), solid organ or bone marrow transplant recipients)
7. Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period
8. Anticipated discharge from the hospital or transfer to another hospital within 48 hours of screening
9. Allergy to OPT101or any component of OPT101 formulation
10. Participation in other interventional clinical trials

11. Pregnancy:

    • positive or missing pregnancy test before first drug intake or day 1
    • pregnant or lactating women;
    • Women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception for the duration of the study
12. Current hospital stay >72h
13. Complicated CAP-associated conditions, such as fungal pulmonary infection, tuberculosis infection, abscess, empyema, significant bilateral pleural effusion, massive pulmonary embolism
14. Weight is over 250lbs

15. Any other condition which the Principal Investigator feels may jeopardize the safety of the patient or the objectives of the study. The Principal Investigator should make this determination in consideration of the patient's medical history and current clinical condition.

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 0.9% Sodium Chloride Injection USP; Placebo will be 50mL normal saline (Sodium Chloride), USP sterile solution provided in a 50mL pre-packaged Intravenous (IV) bag.	Other: Placebo; 0.9% Sodium Chloride Injection USP, Placebo. On the day of administration, a 50mL IV bag containing saline (0.9% Sodium Chloride Injection USP) which will serve as the placebo will be administered via intravenous (IV) infusion over 120 minutes.; Other Names: Placebeo
Experimental: OPT101; OPT101 (15-mer peptide) will be provided across 2 cohorts at 1.1 (cohort 1) and 2.8 mg/kg (cohort 2) doses . On the day of administration, the product will be diluted in saline to result in 50 mL for intravenous (IV) infusion over 120 minutes.	Drug: OPT101; OPT101, is a 15-mer peptide derived from the sequence of mouse CD40L and was designed to target CD40-mediated inflammation. On the day of administration, the product will be diluted in saline to result in 50 mL for intravenous (IV) infusion over 120 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Treatment emergent adverse events will be recorded and assessed by CTCAE v4.0	30 days
Incidence of serious adverse events (SAEs)	SAEs will be recorded and assessed by CTCAE v4.0	30 days
Incidence of TEAEs leading to study drug discontinuation		30 days
Incidence and characteristics of presumed infusion reactions	Recorded as an adverse event	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the serum pharmacokinetics of OPT101	Serum concentrations of OPT101 to determine AUCO-24	30 days
To measure the serum pharmacokinetics of OPT101	Serum concentrations of OPT101 to determine Cmax	30 days
To measure the serum pharmacokinetics of OPT101	Serum concentrations of OPT101 to determine Tmax	30 days
To measure the serum pharmacokinetics of OPT101	Serum concentrations of OPT101 to determine t1/2	30 days
To measure the serum pharmacokinetics of OPT101	Serum concentrations of OPT101 to determine Vz/F	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To observe the changes in degree of sepsis via Pneumonia Severity Index (PSI)	Pneumonia Severity Index (PSI) predicts the need for hospitalization for people with Community Acquired Pneumonia (CAP). Patients are ranked by Risk Class (I , II, III, IV or V). Patients with CAP categorized as Risk Class of I and II can be treated at home. Patients with CAP categorized as Risk Class III may be treated at home or may require a short hospital stay. Patients with CAP categorized as Risk Class of IV and V require hospitalization.	30 days
To observe the changes in degree of sepsis via Sequential Organ Failure Assessment (SOFA) score	SOFA grading, minimum value is 0 (normal) and maximum value is 4 (highest degree of dysfunction/failure). The higher the score, the worse the outcome.	30 days
To observe the changes in degree of sepsis via Cytokine Release Syndrome (CRS) grading	CRS is graded from Grade 1 to Grade 4. Grade 1 is the best outcome and Grade 4 is the worst outcome in terms of change in degree of sepsis. CRS parameters used for grading include fever, hypotension and hypoxia.	30 days
Evaluate Pharmacodynamic Effects of OPT101	Quantitation of Th40 to Treg ratio	30 days
Evaluate Pharmacodynamic Effects of OPT101	Quantitation of peripheral blood B cells	30 days
Evaluate Pharmacodynamic Effects of OPT101	Quantitation of macrophages	30 days
Evaluate Pharmacodynamic Effects of OPT101	Quantitation inflammatory biomarkers	30 days
Evaluate Pharmacodynamic Effects of OPT101	Quantitation of Th40 cells,	30 days

Collaborators and Investigators

• Sponsor: Op-T LLC
• Investigators: Study Director: Herbert B Slade, MD FAAAAI

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Immunomodulator; Community Acquired Pneumonia (CAP); Sepsis; OPT101; Op-T LLC
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pneumonia; Pathological Conditions, Signs and Symptoms; Community-Acquired Infections; Sepsis; Community-Acquired Pneumonia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: OPT101-100-40

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