Clinical trial NCT05501418: Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19
Official title: A Seamless Phase I/IIa Clinical Study to Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With Severe and Critical COVID-19 Condition
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: COVID-19 Infection
Lead sponsor: Ever Supreme Bio Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-15
Enrollment: 75
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to explore the safety and efficacy of using UCMSC01 in patients with COVID-19 infection via IV stem cell administration. The novelty of the current UMSC01 treatment is the single IV infusion of UMSC01 to the worldwide emergency outbreaks of COVID-19. We hypothesize that sufficient UMSC01 retention in lung may modulate the systemic inflammatory responses.

Detailed description: The lead Phase I safety phase will further confirm the safety profile of UMSC01 in 5 COVID-19 patients each at two dose regimens and placebo.

To start the Phase IIa study, data analysis will be performed as soon as the 21-day treatment period has been completed in the three groups. With considerations of the pandemic status and clinical practice, only one of the two active treatment groups will be selected to complete the Phase IIa study, which will recruit 60 patients.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged 20 to 80 years old.
2. Hospitalized severe and critical COVID-19 patients with laboratory confirmation by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal/ oropharyngeal samples collected using standardized method.
3. Pneumonia or interstitial lung damage that is confirmed by chest radiographs or computed tomography.
4. Severe COVID-19 infection which meets any one of the following: 1) dyspnea (PR ≥ 30 times/min), 2) finger oxygen saturation ≤ 93% in the room air and resting state, 3) arterial oxygen partial pressure (PaO2)/oxygen absorption concentration (FiO2) ≤ 300 mmHg, 4) pulmonary imaging which shows that the focus progress \> 50% within 24-48 hours, or
5. Critically severe COVID-19 infection which meets any of the following: 1) respiratory failure treated by mechanical ventilation, 2) shock, 3) combined with other organ failure, 4) patients expected to need ICU monitoring and treatment.
6. High sensitivity C-reactive protein (hs-CRP) serum level \> 4.0 mg/dL.
7. All female patients with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) shown below, for at least 4 weeks after UMSC01 treatment and agree to maintain such contraceptive method(s) for another 4 weeks after UMSC01 treatment.

   1. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
   2. Female sterilization (bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, the reproductive status of the woman should be confirmed by the hormone level assessment.
   3. Male sterilization (at least 6 months prior to screening). For female subjects in the study, the vasectomized male partner should be the sole partner for that subject.
   4. Combination of any two of the following listed methods: (d.1 + d.2 or d.1 + d.3, or d.2 + d.3):

   d.1 Use of oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), such as hormone vaginal ring or transdermal hormone contraception.

   d.2 Placement of an intrauterine device (IUD) or intrauterine system (IUS). d.3 Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

Exclusion Criteria:

1. Pregnancy, lactation, and those who are not pregnant but did not, or unwilling to, take effective contraceptives measures 4 weeks before and after the treatment.
2. Patients with malignant tumors or other serious systemic diseases.
3. Patients with hemoglobin \< 10 g, alanine aminotransferase (ALT) ≥ 5 × ULN, aspartate aminotransferase (AST) ≥ 5 × ULN, alkaline phosphatase (ALP) ≥ 5 × ULN, total bilirubin (TBILI) ≥ 2 × ULN, serum creatinine \> 2.5 mg/dl, platelet counts \< 100,000/μL, WBC \< 3,000 cells/μL, or neutrophil counts \< 1,000/μL at screening.
4. Presence of barotrauma or hemodynamic instability defined as hypotension with diastolic blood pressure \< 90 mmHg or mean arterial pressure (MAP) \< 70 mmHg despite fluid expansion, and vasoactive support or pneumothorax at screening.
5. Uncontrolled hypertension with systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 100 mmHg which, in the investigator's judgment, would not make participation appropriate.
6. Recent history of (within 2 years) ischemic heart disease or cerebrovascular attack, such as myocardial infarction, unstable angina, or stroke.
7. Recent history (within 2 years) of hypercoagulable disorder, antiphospholipid syndrome, pulmonary embolism, or deep venous thrombosis.
8. Condition other than COVID-19 that is projected to limit lifespan to ≤ 1 year.
9. History of drug or alcohol abuse within the past 24 months.
10. Unwilling to commit to follow-up visits.
11. Patients who are participating in other clinical trials with an investigational product.
12. Co-infection of HIV, tuberculosis, influenza virus, adenovirus, and other respiratory infection virus.
13. Patients with other conditions that are not suitable to participate in this clinical study as determined by the investigator.

Primary outcomes:
measure: Two Co-Primary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Two Co-Primary Efficacy Endpoints
timeFrame: 21 days of the treatment period
Secondary outcomes:
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 14 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: through study completion, an average of 1 year
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Efficacy Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Safety Endpoints
timeFrame: 21 days of the treatment period
measure: Secondary Safety Endpoints
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
state: Non-US
Study officials:
affiliation: Ever Supreme Bio Technology Co., Ltd.
name: Woei C Shyu
role: STUDY_DIRECTOR
affiliation: China Medical University Hospital
name: Long Bin Jeng
role: PRINCIPAL_INVESTIGATOR
References: