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.

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.

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