Table 4.
List of drugs and vaccines that are on clinical trials.
| Candidate drug | Mode of action and dose | Existing disease approval | Trial sponsor | Location | Expected result | Phase trial |
|---|---|---|---|---|---|---|
| Hydroxycholoroquine (ID: NCT04329611) [131] | Hydroxychloroquine inhibits acidification of endosomes, deglycosylates receptors of recipient cells, prevents proteolytic processing thus retards entry of virus. Inhibition of cytokine production modulates the host immune system. It also inhibits in host autophagy and lysosomal functionality Dose: Hydroxychloroquine dose of 400 mg po bid on day 1 followed by 200 mg po which will be given twice daily for 4 days |
Malaria, rheumatoid arthritis (RA), lupus | Dr. Michael Hill | University of Calgary | Preliminary trials indicated that it is a potential and safe drug against COVID-19 pneumonia and shorten the disease course about 50%. Later it was found that both these drugs have side effects like allergic reactions, hypoglycemia, cardiomyopathy. On April, 2020 in Brazil 11 patients died due to irregular heart rates. | Phase III |
| Remdesivir (ID:NCT04292899 and NCT04292730) [[132], [133], [134]] | Antiviral Dose: RDV 200 mg on first Day followed by RDV 100 mg for next 4 days together with standard therapy. |
– | Gilead, WHO, INSERM | China, japan | According to US NIAID, remdesivir shows faster recover from COVID-19 in 11 days compared to other drugs. A clinical trial in china, reported on 29thApril several adverse effect of remdesivir in treated patients. | In April 2020, there was 9 phase III clinical trials across the world. |
| Duvelisib (ID:NCT04372602) [135] | Target PI3K and control hyperactivation of innate immune system by affecting macrophage polarization, reducing inflammation in pulmonary and limit the persistence of viral load. Dose: 25 mg twice daily for 10 days, orally |
– | Washington University School of Medicine. | Washington University School of Medicine, Saint Luis, Missouri, United Sates | Current primary outcome reported on 30th April overall survival | Phase II |
| Deferoxamine (ID: NCT04333550) [136,137] | It is a natural product which is isolated from Streptomyces pilosus. It helps in the formation of iron complexes and its mesylate form perform as chelating agent, | – | Kermanshah University of Medical Science | Regenerative Medicine Research Center, Kermanshah University of Medical Science, Iran, kemanshah. | Trial ongoing | Phase I Phase II |
| Favipiravir (ID:NCT04336904) [138] | It targets RNA-dependent RNA polymerase (RdRp) enzymes, which are necessary for the transcription and replication of viral genomes. Dose: Day 1:1800 mg, BID is given at 1800 mg on day 1 and day 2 followed by TID dose at 600 mg for 14 days. Thereafter: 600 mg, TID, for a maximum of 14 days. |
Used before against Ebola virus and lassa virus. | Giuliano Rizzardini | Asst Fatebenefratelli Sacco, Milan Ilaty | the normalization of pyrexia, normal respiratory rate and relief from cough is maintained for at least 72 h. | Phase III |
| Tocilizumab (ID:NCT04345445) [139] | Human monoclonal antibody against IL-6 receptor. Dose: Intravenously administered with a concentration of 8 mg/kg (body weight) once, within 60 min. |
This drug has been used against immune suppression and in RA. | Genentech-hoffmann La Roche | Multiple countries | As per 8-point WHO scale, improvement of more than 2 point is observed. | Phase II |
| Sarilumab (ID:NCT04327388) [140] | Human monoclonal antibody against IL-6 receptor. Dose: Sarilumab Dose 1 given intravenously one time on Day 1 |
RA | Regeneron-Sanofi | Multiple countries | Patients improvement in oxygenation. | Phase II/ Phase III |
| Dapagliflozin (ID:NCT04350593) [141,142] | It acts as a sodium glucose cotransporter inhibitor. Dose: Dapagliflozin 10 mg daily |
Hypoglycemia | Saint Luke's Mid America Heart Institute, Astrazeneca | Multiple countries | No detoriation in functionality of organs are observed in hospitalized patients at 30th day. | Phase III |
| Recombinant human angiotensin-converting enzyme 2 (rhACE2) (ID:NCT04287686) [143] | It is a monocarboxy-peptidase that metabolizes several peptides, including the degradation of angiotensin II, and contributes to cardiovascular effect. Dose: Together with standard treatment0.4 mg/kg IV BID given for 7 days. |
– | Hospital of Guangzhou Medical University | Guangdong, China | 24–48 h of Pulmonary imaging showed that progression of the lesions are more than 50% and the patients were managed as severe | Phase II |
| Clevudine with combination hydroxychloroquine (ID:NCT04347915) [144] | Clevudine is an antiviral drug used against hepatitis B. Dose: Clevudine 120 mg once daily for 14 days (Hydroxychloroquine 200 mg twice daily for 14 days. |
Hepatitis B | Bukwang Pharmaceutical | Trial ongoing | Phase II | |
| Drug: FT516 (ID:NCT04363346) [145] | FT516 is a cryopreserved NK cell product of an iPSC that was transduced with ADAM17 non-cleavable CD16 (Fc receptor). Dose: Firstly, FT516 is administered at 9 x107 cells/dose in low concentration Secondly, FT516 is first given at low dose (9 x107 cells/dose) additionally at Day 4 it is provided in medium dose at (3 x 108 cells/dose) Thirdly, along with the low and medium doses, a higher dose of drug is given at day 7 (9 x 108 cells/dose) |
Cancer | Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota, United States. | Trial ongoing | Phase I |
| DAS181 (ID: NCT04324489) [146] | Enzymatically cleaves viral receptors on host cells Dose: From day 1 to 10, once or twice a day, for 10 consecutive days, a total of 9 mg (7 mL) |
Parainfluenza and other flu viruses including resistant strains | Renmin Hospital of Wuhan University | China | Better clinical outcomes | Completed |
| Losartan (ID: NCT04335123) [147] | – Dose: 25 mg for first 3 days folllowed by 50 mg QD till study completion |
– | University of Kansas Medical Center | Kansas City, United States. | Trial ongoing | Phase I |
| Ivermectin with Nitazoxanide (ID:NCT04360356) [[148], [149], [150]] | Antiviral drug that affects the viral RNA and DNA replication in a broad spectrum. Dose: Ivermectin 200 mcg/kg once orally on empty stomach plus Nitazoxanide 500 mg twice daily orally with meal for 6 days |
– | Tanta University | – | Trial ongoing | Phase II |
| Transfusion of SARS-CoV-2 Convalescent Plasma. (ID:NCT04372979) [151,152] | Convalescent plasma contains antibody against SARS-CoV-2. Dose: Intravenous |
– | Direction Centrale du Service de Santé des Armées | France | Trial ongoing | Phase III |
| Isotretinoin (ID:NCT04361422) [153] | Inhibitors of PLpro, a protein encoded by SARS-CoV-2 Dose: Orally |
Used to decrease virema in HIV+ patients | Tanta University | – | Clinical clearance Change in COVID-19 virus load |
Phase III |
| Colchicine (ID:NCT04375202) [154] | Non-selective inhibition of NLRP3, a pathophysiologic component of SARS-CoV Dose: 0.5 mg every 8 h for 30 days, orally (Tablet) |
Cardiovascular disease | University of Perugia | Italy | Trial ongoing | Phase II |
| Ruxolitinib (ID:NCT04355793,NCT04338958) [[155], [156], [157]] | Treat the cytokine storm and hyperinflammation in COVID-19 patients Dose: 5 mg orally twice daily |
Treat bone marrow disorders like myelofibrosis | Incyte corporation University of Jena |
USA | Reduce 25% hyperinflammation caused due to the cytokine storm | Phase II |
| Sildenafil (ID:NCT04304313) [158] | Relaxes the muscles of the lungs by increasing the potency of nitric oxide gas to widen the blood vessels resulting in more oxygen inhalation Dose: 0.1 g daily for 14 days, orally |
Erectile dysfunction | Tongji hospital | China | Respiratory symptom remission Decrease in fever C-reactive protein recovery |
Phase III |
| Sirolimus (ID: NCT04341675) [159] | mTOR inhibitor, immune suppressor Dose: 6 mg on first Day then 2 mg daily for next 13 days. |
Used for preventing organ transplant rejection and lymphangioleiomyomatosis (LAM) | University of Cincinnati | USA | Trail ongoing | Phase II |
| Peginterferon Lambda-1a (ID:NCT04331899) [160] | Reduces viral shedding of SARS-CoV-2 Dose: One subcutaneous injection of 180 ug |
Hepatitis B Virus infection Hepatitis C virus infection |
Stanford University | USA | Trial ongoing | Phase II |
| Rintatolimod and IFN Alpha-2b (ID:NCT04379518) [161] | Rintatolimod is a dsRNA designed to mimic viral infection by activating immune pathways and IFN Alpha-2b activate immune responses and both participate in limiting viral replication and shedding Dose: IV rintatolimod for 2.5–3 h together with IV of recombinant interferon alpha-2b over 20 min on days 1, 3, 5, and 8 if there will be the disease progression or no unacceptable toxicity treatment will be followed up at 14th day and 28th day |
Viral infections | Roswell Park Center Cancer Institute | USA | Trial ongoing | Phase I/ IIa |
| l-ascorbic acid (ID: NCT04357782) [162] | Reduce inflammation, ARDS, reduce supplement oxygenation, reduce risk respiratory failure which intubation Dose: 50 mg/kg IV given every 6 h for 4 days (16 total doses), |
Sepsis | Hunter Holmes Mcguire Veteran Affairs Medical Center | Virginia, USA | Trial ongoing | Phase I/ II |
| mRNA1273 (ID:NCT04283461) [163,164] | A lipid nanoparticle (LNP) encapsulated with mRNA encoding full length S protein of SARS-CoV-2. Dose: 10/25/50/100/250 mcg mRNA1273 with .05 mL intramuscular injection in deltoid muscle. |
– | National Institute of Allergy and Infectious Disease (NIAID) | – | Trial ongoing | Phase I |
| INO-4880 (ID:NCT04336410) [165] | It is a DNA vaccine against whole- length S protein of SARS-CoV-2. Dose: intradermal injection of 1.0 mg of INO-4800 |
– | Inovio Pharmaceuticals | – | Trial ongoing | Phase I |
| ChAdOx1 nCoV-19 COVID-19 (ID:NCT04324606) [166,167] | Adenovirus encoding full-length S protein Dose: One dose of 5 x 10^10vp |
– | University of Oxford | UK | Trial ongoing | Phase II |
| COVID-19 LV- SMENP-DC (ID:NCT04276896) [168] | Lentivirus infected dendritic cells with SMENP minigenes that express COVID-19 antigens and activated CTLs. | – | Shenzhen Geno-Immune Medical Institute | China | Trial ongoing | Phase II |
| SARS-Cov-2 (ID:NCT04368988) [169] | Nanoparticle vaccine of spike (S) protein of SARS-CoV-2 | – | Novavax | – | Trial ongoing | Phase I |
| BNT162a1, b1, b2, c2 (ID:NCT04368728) [170] | It is a LNP encapsulated mRNA vaccines with mRNA targets for both larger S sequence and RBD. Dose:0.5 mL intramuscular injection. |
– | BioNTech SE and Pfizer, Inc. | – | Trial ongoing | Phase I |
| Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (ID:NCT04313127) [72] | Adenovirus type 5 encoded with full length S protein | – | CanSino Biologics, Inc. | China | The vaccine is tolerable and immunogenic at 28 days post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. | Phase I |
| bacTRL-Spike-1 (ID:NCT04334980) [171] | Live Bifidobacteriumlongum, engineered for the delivery of plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2. | – | Symvivo Corporation | Trail ongoing | Phase I | |
| Mrna-1273 vaccine (ID: NCT04470427) [164] | Neutralizing activity against recombinant vesicular stomatitis virus (rVSV)–based SARS-CoV-2 (a pseudovirus-based model) in serum samples of new variants of the virus. Dose: Participants will receive 1 intramuscular (IM) injection of 100 microgram (ug) mRNA-1273 on Day 1 and on Day 29. |
– | ModernaTX, Inc. | Efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273. | Phase III | |
| Decitabine for Coronavirus (COVID-19) Pneumonia - Acute Respiratory Distress Syndrome (ARDS) Treatment (ID: NCT04482621) [172] | Works as hypomethylating agents, affecting replication Dose: 10 mg/m^2/day IV day x 5 days (1 cycle only) intravenously |
Myelodysplastic syndrome (MDS) | Johns Hopkins University | USA | Recruiting | Phase II |
| Xuanfei Baidu granules (XFBD), Traditional Chinese medicine (TCM) (ID: NCT04810689) [173] | Acts as anti-coagulant agent which dissolves blood clots, relieves shortness of breath by relaxing the tracheal muscles. Dose: Orally twice daily for 14 days, 1 h after food in the morning and at night with at least 8 h in between doses |
Used for fever recovery and suppress of cough by clearing phlegm | Darcy Spicer, University of Southern California | USA | Recruiting | Phase II |
| STI-5656 (Abivertinib Maleate) (ID: NCT04528667) [174] | Third-generation EGFR tyrosine kinase inhibitor and BTK inhibitor. Dose: Subjects receive either 100 mg of STI-5656 or placebo daily for 7 days |
Advanced non-small cell lung carcinoma | Sorrento Therapeutics, Inc. | Brazil | Recruiting | Phase II |
| Desferal (ID: NCT04333550) [136,175] | Acts as chelating agent Dose: Intravenous injection |
Patients with acute or chronic iron and aluminium toxicity | Kermanshah University of Medical Sciences | Iran | Recruiting | Phase I/II |
| Pulmozyme/Recombinant human deoxyribonuclease (rhDNase) (ID: NCT04445285) [176] | Reduces sputum viscoelasticity. Dose: 2.5 mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 h for five (5) consecutive days; a total of five (5) doses |
Cystic fibrosis | Jon Simmons, University of South Alabama | USA | Recruiting | Phase II |
| COVID-19 vaccine (COVAXIN) (BBV152) (ID: NCT04641481 [177] | The vaccine is used along with immune stimulants, commonly known as vaccine adjuvants (Alhydroxiquim-II), to improve immune response and longer-lasting immunity Dose: 0.5 mL per dose |
– | Bharat Biotech International Limited | India | Active, not recruiting | Phase III |
| Dornase Alpha (Pulmozyme) (ID: NCT04432987) [178] | It helps in clearing the NETs created by neutrophils in the lungs Dose: Drug will be administered at a dose of 2.5 mg/2 times per day for 7 days |
Cystic fibrosis | Acibadem University | Istanbul, Tutkey | Recruiting | Phase II |
| AZD7442 (A combination of AZD8895 and AZD1061) (ID: NCT04723394) [179] | mABs affects the RBD of viral S protein. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which can prolong their potential prophylactic benefit, and minimize Fc effector function. Dose: Single dose (× 2 separate IM injections) of 600 mg of AZD7442. |
– | AstraZeneca | England, UK | Recruiting | Phase III |
| Emricasan (ID:NCT04803227) [180] | Peripheral blood lymphocytes of COVID-19 patients overexpress caspase-1. Caspase-1 plays a role in a form of cell death called pyroptosis. EMR inhibits pyroptosis, thus it serves as a pan caspase inhibitor Dose: 25 mg BID (days 1–14). Oral (capsule) administration. |
– | Histogen | SUNY Downstate Health Sciences University Brooklyn, New York, United States |
Recruiting | Phase I |
| Sirolimus (ID: NCT04461340) [181] | Inhibits IL-2 and other cytokine receptor-dependent signal transduction mechanisms Dose: Oral dose of 6 mg on day1 followed by 2 mg daily for 9 days |
Head and Neck Lymphatic Malformations | Alexandria University | Egypt | Recruiting | Phase II |
| Sitagliptin (ID: NCT04382794) [182] | Inhibits the action of dipeptilpeptidase-4 expressed at parenchyma and lung interstitium level | Type -II diabetes | University of Milan | Italy | Lessens the activity of proinflammatory cytokines, growth factors and vasoactive peptides | Completed |
| Rivaroxaba (ID:NCT04757857) [183] | Acts as anticoagulants Dose: 1st to the 14th day, a dose of 10 mg of rivaroxaban - OA (Oral Administration). |
Thrombosis and pulmonary embolism | Alemão Oswaldo Cruz | Brazil | Recruiting | Phase IV |
| Dendritic Cell Vaccine (ID: NCT04685603) [184] | – | Cancer | Indonesia-MoH | Indonesia | Recruiting | Phase I |
| AZD1222 (ID:NCT04516746) [185] | Recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein. Dose: 0.5 mL of 2 dose on day 1 and day 29. |
– | AstraZeneca | United States | Active, not recruiting | Phase III |
| SII-ChAdOx1 nCoV-19 [186] | Recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2- Spike protein. Dose: 0.5 ml of 2 dose on day 1 and day 29. |
– | Serum Institute of India | India | – | Phase III |
ADAM 17, a disintegrin and metalloproteinase 17; CTLs, cytotoxic T lymphocytes; dsRNA, double stranded RNA; EGFR, epidermal growth factor receptor; IFN, interferon; LAM, lymphangioleiomyomatosis; LNP, lipid nanoparticle; mTOR, mammalian target of rapamycin; NETs, neutrophils extracellular traps; NK, natural killer; NLRP 3, NLR family pyrin domain containing 3; PI3K, phosphatidylinositol 3 kinase; RBD, receptor binding domain; RA, rheumatoid arthritis; RdRp, RNA dependent RNA polymerase; S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus.