Evaluation of the Safety and Efficacy of XoGlo Pro, a Placental Mesenchymal Stem Cell-derived Extracellular Vesicles in Treating COVID-19 Symptoms

The study is a prospective, stratified, randomized, double-blinded, placebo-controlled, parallel-group, single-dose clinical study with the primary objective of evaluating the safety of XoGlo® PRO (isolated, placental mesenchymal stem cell \[MSC\]-derived extracellular vesicles \[EVs\]) administered intravenously (IV) for the treatment of Coronavirus Disease 2019 (COVID-19) symptoms in adults with mild-to-moderate illness. The secondary objective of the study is to evaluate the efficacy of treatment between the XoGlo® PRO treatment arm and the placebo arm.

Primary and secondary objectives will be evaluated overall and stratified by time between COVID-19 symptom onset and treatment administration (symptomatic days prior to dose), age, sex, and vaccination status.

The time from the onset of COVID-19 symptoms to single-dose treatment must be greater than 2 days but no more than 10 days. Four (4) symptom-time cohorts are defined based on the time from symptom onset to single-dose treatment administration: 3-4 days, 5-6 days, 7-8 days, and 9-10 days. Each symptom-time cohort will include 16 subjects (8 XoGlo® PRO treatment arm subjects and 8 placebo arm subjects). Vaccination status between the treatment arms and symptom-time cohorts will be balanced using stratified randomization.

As defined by the Centers for Disease Control and Prevention (CDC), vaccination status will be categorized into four groups:

Optimally Protected: A person is considered optimally protected when fully vaccinated and up to date with recommended booster doses, if eligible.

Fully Vaccinated: A person is considered fully vaccinated two weeks after receiving the second dose in a two-dose vaccine series (e.g., Pfizer-BioNTech or Moderna vaccines) or two weeks after receiving a single-dose vaccine (e.g., Johnson \& Johnson/Janssen vaccine).

Partially Vaccinated: A person is considered partially vaccinated when at least two weeks have passed since receiving the first dose of a COVID-19 vaccine requiring a two-dose series.

Unvaccinated: A person is considered unvaccinated if they have not received any doses of a COVID-19 vaccine.

A subject's prior COVID-19 infection history before study participation will not be used as a randomization stratification factor. It is expected that a similar proportion of participants with prior COVID-19 infection will be distributed between treatment groups based on the prevalence of previous infection within the population. However, information regarding previous COVID-19 infection history, including date and number of prior infections, will be collected for descriptive and predictive analyses. Current active symptomatic COVID-19 infection is required for study inclusion.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the ability to differentiate into multiple cell types. MSCs have demonstrated the capacity to modulate immune responses and support the regeneration of diseased or damaged cells and tissues in preclinical and clinical studies.

Extracellular vesicles (EVs) are naturally occurring biological messengers that contain complex cell-signaling information within extracellular nanovesicles produced by living cells. EVs produced by MSCs mimic components of the parent cell secretory profile and have been suggested to have a potential role in modulating inflammatory responses associated with viral infections, including inflammatory cytokine expression, lymphocyte activation, and signaling pathways involved in inflammation and disease progression.

Unlike live MSCs, MSC-derived EVs are acellular and have not been associated with risks related to cellular replication, malignant transformation, or graft-versus-host disease. MSC-derived EVs may also provide advantages related to manufacturing scalability, storage, and distribution.

Isolated, placental MSC-derived EVs, also known as exosomes, have been investigated for their potential role in the treatment of COVID-19 through multiple mechanisms. The protein and ribonucleic acid (RNA) contents of MSC-derived EVs contribute to their biological properties and may help modulate excessive immune responses associated with COVID-19 infection, support tissue repair mechanisms, and reduce apoptosis of alveolar epithelial cells.

• IV infusion using an isolated, placental, mesenchymal stem cell derived EVs (Biological), also known as Exosome, Extracellular Vesicles, EVs, XoGlo Pro: Single IV infusion of the drug product XoGlo Pro
• Placebo IV administration (Biological): Placebo IV infusion of normal saline

Primary outcomes

• Incidence of Treatment-Emergent Adverse Events (TEAEs) Following a Single Intravenous Dose of XoGlo® Pro [Baseline through 180 days post-dose]: Number and percentage of participants experiencing one or more treatment-emergent adverse events (TEAEs) following administration of a single intravenous dose of XoGlo® Pro (5 mg in 5 mL). Adverse events will be assessed from the time of investigational product administration through the end of the study period.

Secondary outcomes

• Time to Resolution of COVID-19 Symptoms Following a Single Intravenous Dose of XoGlo® Pro [Baseline through Day 180 post-dose]: Time from investigational product administration to resolution of COVID-19 symptoms as measured using the protocol-defined 14-item COVID-19 symptom assessment instrument. Symptom resolution will be assessed by comparing the time to resolution between the XoGlo® Pro treatment arm and placebo arm.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Adult subjects of either gender aged more than 18 years.
2. Body Mass index (BMI) between ≥25 and ≤39.9 kg/m2.
3. Duration (in days) of COVID-19 symptoms prior to randomization is a > 2 days and ≤ 10 days of COVID-19 symptoms.
4. Two (2) positive (rapid) antigen diagnostic tests for SARS-CoV-2 (tests listed under FDA EUA) and administered within 2 hours of each other. Enrolled subjects will undergo subsequent molecular standard reverse transcriptase polymerase chain reaction (rt-PCR) assay. Enrolled subjects with a negative PCR test will be replaced by other individuals.)
5. Subjects with a minimal baseline severity score for COVID-19-related symptoms defined as at least two symptoms with a score of 2 or higer, using normalized grading scale.
6. Female subjects of non-childbearing potential (e.g., non fertile, pre-menarche, permanently sterile \[e.g., underwent hysterectomy, bilateral salpingectomy or bilateral ovariectomy\] or post-menopausal \[history of no menses for at least 12 months without an alternative medical cause\] or Woman of childbearing potential* with a negative serum or urine pregnancy test

Exclusion Criteria:

1. Subjects who test positive for SARS-CoV-2 using a virologic test but have no symptoms consistent with COVID-19. (Asymptomatic or presymptomatic infection).
2. Subjects who have SpO2 <94% on room air at sea level (Severe illness).
3. Subjects who have respiratory failure (Critical illness).
4. Subjects who have septic shock (Critical illness).
5. Subjects who have multiple organ dysfunction (Critical illness).
6. Subjects presenting with an underlying medical condition or risk factor that conclusively disposes that subject to a higher risk for progression to severe COVID-19, as per the CDC's Systematic Review Process.
7. Subjects hospitalized within the previous 15 days.
8. Subjects discharged from the Emergency Room within the previous 15 days.
9. Subjects not expected to survive for three (3) months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases.
10. Less than 18 years.

• Dr. Azza Halim, MD, Study director, Kimera Labs Inc. - CMO