Efficacy of Intravenous Infusions of Stem Cells in the Treatment of COVID-19 Patients

NCT04437823 | Completed Phase 2 DMC

• 1 other identifier: JB&RSC-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Stem cell therapy has emerged as a revolutionary treatment for diseases that were considered untreatable only a few years ago. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been shown to repair damaged liver, kidney, heart, pancreas, skin, cartilage, and cornea in animal models and several human trials. In addition to cellular replacement through regeneration, UCMSCs mediate through paracrine signaling pathways resulting in immune modulation. Clinical manifestations of coronavirus disease 2019 (COVID-19), are believed to arise from septic shock and cytokine storm that cause acute respiratory dysfunction and acute cardiac injury. There is presently no cure for the COVID-19 viral disease; however, multi-treatment strategies are being examined. During the past two months, four reports were published that suggest, mesenchymal stem cells (MSCs), owing to their powerful immunomodulatory ability, may prevent the cytokine storm and thus reduce the COVID-19 related morbidity. All studies reported that COVID-19 patients responded favorably to MSCs therapy. These reports, taken together with the previous successes of stem cell therapy in animal models, the investigators, a seven-institution consortium, propose to explore the efficacy of UCMSC treatment in COVID-19 patients at Jinnah hospital, Lahore. The investigators propose to administer UCMSCs in patients with acute pulmonary inflammation due to COVID-19 infection with moderate to severe symptoms. In the first cohort of 15 patients, UCMSCs will be administered with three intravenous infusions of 500,000 UCMSCs per Kg body weight each on days 1, 3, and 5. The second group of five patients serving as control will only receive standard treatment. During the 30-day post-infusion period, a battery of tests will be performed to evaluate the safety and efficacy of the UCMSCs treatment. In parallel, the investigators propose a comparative study to determine COVID-19 viral count by quantitative real-time PCR and through viral coat protein ELISA, developed in the investigator advisor lab (Dr. Tauseef Butt, Progenra Inc. Philadelphia, USA) with the ultimate objective to locally developing a rapid diagnostic assay.

Conditions

Corona Virus Infection

Keywords

COVID-19; Stem Cells treatment

Outcome Measures

Primary Outcomes (2)

• Safety and efficacy assessment of infusion associated adverse events

  Number of participants with significant side effects in stem cell treated group

  Day 01 to Day 30

• Chest Radiograph or Chest CT Scan

  Assessment of Pneumonia improvement as a result of stem cell infusions

  Day 01 to Day 30

Secondary Outcomes (4)

• COVID-19 Quantitative Real Time PCR

  Day 01 to Day 30

• Sequential Organ Failure Assessment (SOFA) Score

  Day 01 to Day 30

• Rate of mortality

  Day 01 to Day 30

• Clinical Respiratory Changes

  Day 01 to Day 30

Study Arms (2)

Group 1 : Treatment

EXPERIMENTAL

Fifteen (15) subjects will be treated with three intravenous infusion (IV) of 5 x 10\^5 UCMSCs per Kg body weight delivered via peripheral intravenous infusion on days 1, 3 and 5 besides the standard care (SOC).

Biological: Intravenous Infusions of Stem Cells

Group 2: standard care

NO INTERVENTION

Five (5) subjects will be treated under Standard of Care (SOC) .

Interventions

Intravenous Infusions of Stem Cells BIOLOGICAL

Cultured stem cells will be injected at days 1, 3 and 5 intravenously. While patients will be monitored and evaluated for various hematological and organ functions at baseline (day 0) and days 1, 3, 5, 7, 14, 21 and 30

Group 1 : Treatment

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent
• Male or female subjects age \>18 years at the time of signing the Informed Consent Form
• Must have a clinical diagnosis of COVID-19, with at least one of clinical symptoms (e.g., fever ≥38°C, fatigue, cough) and a positive result by the reverse-transcription polymerase chain reaction (RT-PCR) testing or equivalent
• Individuals with moderate to severe COVID-19 symptoms
• Adequate venous access
• For female patients only, willingness to use recommended birth control until 6 months post-treatment
• Must agree to comply with all study requirements and be willing to complete all study visits
• Need in-patient admission

You may not qualify if:

• A female who is pregnant, nursing, or of child-bearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening and prior to infusion.
• Inability to perform any of the assessments required for endpoint analysis
• Have known allergies to penicillin or streptomycin
• Have a clinical history of malignancy within 3 years (i.e., subjects with prior malignancy must be disease-free for 3 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs; - History of drug abuse (illegal "street" drugs except for marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
• Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.

Sponsors & Collaborators

• Jinnah Hospital: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Jinnah Hospital

Lahore, Punjab Province, 54550, Pakistan

Location

Related Publications (6)

• Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr.

  PMID: 32257537 BACKGROUND

• Atluri S, Manchikanti L, Hirsch JA. Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use. Pain Physician. 2020 Mar;23(2):E71-E83.

  PMID: 32214286 BACKGROUND

• Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. No abstract available.

  PMID: 32194981 BACKGROUND

• Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020 Mar 13;7(1):11. doi: 10.1186/s40779-020-00240-0.

  PMID: 32169119 BACKGROUND

• Riazuddin S et al.,. Book chapter: Stem cells for the repair of damaged skin and cartilage, in Book: Stem Cells - From Drug to Drug Discovery. Ed. by Haider, Khawaja Husnain; ISBN# 978-3-11-049376-4; March 2017

  BACKGROUND

• Riazuddin S et al., Cell therapy for liver regeneration. In , (Eds.), Stem Cells - From Hype to Real Hope (pp. 130-145). Berlin, Boston: De Gruyter. https://doi.org/10.1515/9783110587043-007; Book DOI: https://doi.org/10.1515/9783110587043; Online ISBN: 9783110587043; © 2018 Walter de Gruyter GmbH, Berlin/Munich/Boston.

  BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Moazzam N Tarar, MBBS, FCPS

  Jinnah Burn & Reconstructive Surgery Center, Lahore

  PRINCIPAL INVESTIGATOR

• Azra Mehmood, PhD

  Centre of Excellence in Molecular Biology, Lahore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished National Professor

Model Details: Group 1 (15 subjects) Fifteen (15) subjects will be treated with three intravenous infusion (IV) of 5 x 10\^5 (per Kg body weight) UCMSCs delivered via peripheral intravenous infusion on days 1, 3 and 5 besides the standard care (SOC). Group 2 (5 subjects) Five (5) subjects will be treated under SOC. From two subjects in group 1 will not be treated 24hrs apart. Patients will be randomized in a 1:3 ratio (SOC: UCMSC).

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 18, 2020
• Study Start: June 1, 2020
• Primary Completion: October 31, 2021
• Study Completion: November 30, 2021
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: At the end of completion of the study
• Access Criteria: Available online

Locations

PA (1)