Mesenchymal Stem Cell Infusion for COVID-19 Infection

Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)

Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Mesenchymal stem cells; Other: Placebo

Detailed Description

All patients will receive 2x10^6 cells/kg on days 1 and day 7 (if needed). The study will be divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2 groups (5 Treatment arm; 5 Control Arm) and receive 2 x10^6 cells/kg MSCs on days 1 and 7 in addition to standard care. Thereafter, the trial committee will meet and evaluate all collected safety and efficacy information to decide about crossover of Control arm to treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects will be included in the study and treated according to protocol.

Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml bone marrow will be collected from iliac crest using aseptic technique in syringes primed with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS) and MSCs will be separated using density gradient centrifugation. After resuspension the cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for future use or infused immediately.

Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious Disease Specialist, Clinical Hematologist.

1. Demand for MSCs will be initiated on pre-designated forms , signed by Critical care Specialist Clearly indicating indication of MSCs.
2. Request form will be sent Stem Cell Lab.
3. Incharge stem Cell Lab will authorize issuance of the MSCs dose.
4. Stem Cell Lab will issue the dose Administration of MSCs

1. Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on supportive care

Proposed usage:

Because of the very limited availability of MSCs, their usage has to be rationalized by MDT comprising of pulmonologist, critical care specialist and clinical haematologist and Infectious disease specialist.There is not enough evidence to put forth therapeutic recommendations however, treatment decisions can be made on case to case basis after MDT.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xanab akram; Phone Number: 03325346564; Email: xanab.akram@gmail.com

Study Locations

• Pakistan
  • Punjab
    • Rawalpindi, Punjab, Pakistan, 46000
      • Recruiting
      • NIBMT
      • Contact: Xanab Akram; Phone Number: 03325346564

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, aged ≥ 10years
2. Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
3. Moderate illness: In compliance with the 2019-coronavirus pneumonia diagnosis standard [according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and world health organization (WHO) 2019 new coronavirus guidelines standards]: (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
4. Critically ill : Respiratory failure, Septic Shock, muti-organ dysfunction syndrome (MODS)

Exclusion Criteria:

1. Patients with systemic autoimmune diseases
2. Not consenting for clinical trial
3. Those declared not for resuscitation due to underlying comorbid or current critical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stem cells; 10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care	Drug: Mesenchymal stem cells; 1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care; Other Names: MSCs
Placebo Comparator: Placebo; Only supportive care will be given to 10 patients	Other: Placebo; 100 ml of normal saline will be given intravenously to control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Assessment of Overall survival at 30 days post intervention	30 days post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement	days required for oxygen support independence after intervention	30 days
Time of COVID19 PCR negativity	PCR testing to check PCR negativity	day 1,3,7,10, 14
Radiological improvement (day 15 and day 30 assessment)	Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19	day 15 and day30
days required to discharge from hospital	number of days required for discharge from hospital	30 days post admission

Collaborators and Investigators

• Sponsor: Dr. Zaineb Akram
• Investigators: Study Chair: xanab akram, NIBMT

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Anticipated): August 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 21, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 27, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Survival; Coronavirus; Mesenchymal Stem Cells
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: NIBMT-MSc-COVID-2020

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