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

JB&RSC-01

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.

2020-06-01

2021-10-31

2021-11-30

Completed

Early phase I

5

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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).\n\nGroup 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).', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 5, 'type': 'ACTUAL'}}

2023-10-17