COVID-19Phase 1/2DEFINENCT04473053
DEFINE - Evaluating Therapies for COVID-19
A Phase 1/2 study testing Nafamostat Mesilate, TD139 and Allogeneic SARS-CoV-2 VSTs in people with COVID-19, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus, SARS CoV2 and is a serious condition with high mortality in hospitalised patients, for which there is no currently approved treatment other than supportive care. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Nafamostat Mesilate, TD139 and Allogeneic SARS-CoV-2 VSTs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Jul 2020to 30 Apr 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Provision of informed consent from the patient or representative
- Aged at least 16 years
- If the patient is of child bearing potential, the patient, and their partner(s), agree to use medically-accepted double-barrier methods of contraception (eg, barrier methods, including male condom, female condom or diaphragm with spermicidal gel) during the study (if randomised to a treatment arm) and for at least 90 days after termination of study therapy. A vasectomised partner would be considered an appropriate birth control method provided that the partner is the sole male sexual partner and the absence of sperm has been confirmed.
- COVID-19 positive
Who cannot join
- Current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled cardiac disease (NYHA class IV), uncontrolled renal disease (eGFR <30 mL/min/1.73 m2), severe liver dysfunction (ALT/AST >5x ULN) or bone marrow failure (Hb <80 g/L AND ANC<0.5 mm3 AND platelet count <50,000 uL)
- Women who are pregnant or breastfeeding.
- Participation in another clinical trial of an investigational medicinal product (CTIMP)
- Known hypersensitivity to the IMP or excipients (e.g. lactose)
- Pre-existing or Cconcomittant use of off-label treatments for COVID-19 that are not recognised as locally approved standard care.
- Significant electrolyte disturbance (hyperkalaemia potassium >5.0 mmol/L or hyponatraemia sodium < 120mmol/L)
Show all 15Show fewer
- Patient currently receiving potassium sparing diuretics that cannot be reasonably withheld
- Patient currently receiving prophylactic or therapeutic anticoagulantsanticoagulation or antiplatelet agents that cannot be reasonably withheld if randomised to Nafamostat
- Patients (or their partners) planning on donating sperm/eggs during the trial period
- Ongoing dialysis
- History of serious liver disease (Child Pugh score > 10)
- Hemoglobin < 80 g/L
- Any known allergy to the IMP/excipients
- Severe uncontrolled diabetes mellitus
- In the Investigator's opinion, patient is unwilling or unable to comply with drug administration plan, laboratory tests or other study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus, SARS CoV2 and is a serious condition with high mortality in hospitalised patients, for which there is no currently approved treatment other than supportive care. Urgent investigation of potential treatments for this condition is required.
This protocol describes an overarching and adaptive trial designed to provide safety, pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biological surrogates of efficacy which may support further development and deployment of candidate therapies in larger scale trials of COVID-19 positive patients receiving normal standard of care.
Read more
Given the spectrum of clinical disease, community based infected patients or hospitalised patients can be included. Products requiring parenteral administration will only be investigated in hospitalised patients. Patients will be divided into cohorts, a) community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computed tomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiring assisted ventilation. Participants may be recruited from all three of these cohorts, depending on the experimental therapy, its route of administration and mechanism of action. The relevant cohort(s) for any given therapy will be detailed in the therapy-specific appendix.
Candidate therapies can be added to the protocol and previous candidates removed from further investigation as evidence emerges. The trial will be monitored by an independent Data Monitoring Committee (DMC) to ensure patient safety.
Each candidate cohort will include a small cohort of patients randomised to candidate therapy or existing standard of care management dependent on disease stage at entry. Cohort numbers will be defined in the protocol appendices.
This is a Phase IIa experimental medicine trial and as such formal sample size calculations are not appropriate.
Read the detailed description
This trial platform aims to support the repurposing of promising therapeutic assets with prior use in humans but without prior information on use in COVID-19, to determine the PK-PD profile of the agent, compared to standard of care supportive therapy, in small cohorts of COVID-19 patients. The results of these studies are intended to provide initial safety, pharmacokinetic and pharmacodynamic data and experimental medicine data to support further evaluation in existing national and international trial networks for candidates demonstrating appropriate impact on the dynamic marker of interest. The key interception is to mitigate the lung damage in patients with COVID-19 that leads to respiratory failure. As such, the assets in this programme will focus on abrogating putative mechanisms implicated in COVID-19 respiratory disease.
Existing approaches in clinical trials involve novel or repurposed antivirals or immunomodulatory approaches involving agents such as corticosteroids, interferon-β or hydroxychloroquine. A major limitation in the design of many early clinical trials is the limited amount of mechanistic data from patients with COVID-19. Mechanisms have been inferred from animal models, related infections or clinical syndromes. These approaches have infrequently translated to human disease. For example, remdesivir efficacy in animal models of Ebola Virus Disease (EVD) did not translate to human disease and hydroxychloroquine antiviral affects in vitro have not translated to humans against other viruses. Some drugs, such as repurposing of the anti-retroviral protease Kaletra, are still being pursued despite uncertain mechanism and despite evidence that this aspartyl protease cannot bind to the cysteine chymotrypsin-like protease that is Kaletra's putative target in COVID-19.
There is a clear and urgent need to pursue experimental medicine studies in humans to establish a solid mechanistic basis for rapid evaluation, including in existing clinical trial platforms against COVID-19 (e.g DoH RECOVERY and NIHR-CLRN industry adopted studies).
The trial will be as flexible as possible to ensure a broad range of patients can be recruited and candidate therapies can be added or removed as evidence emerges. The interim trial results will be monitored by an independent DMC to evaluate any patient safety signals.
As COVID-19 follows a variable clinical path in individual patients, the protocol is designed to enable inclusion of patients across the disease stages. The trial is intended to provide mechanistic data from patients receiving standard of care therapy and from patients treated with the therapy candidates. The study will enable delivery of pharmacokinetic information and effects of standard of care and candidate agents on surrogate biomarkers of the disease process and the specific drug target.
- Conditions
- COVID-19
- Being tested
- Nafamostat Mesilate, TD139, Standard care, Allogeneic SARS-CoV-2 VSTs
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nafamostat MesilateDrug
Nafamostat has been shown to have potential antiviral effects against MERS CoV and is thought to possibly inhibit SARS CoV2 infection via inhibition of viral entry due to inhibition of TMPRSS2. In addition, nafamostat has potent anticoagulant properties which may provide benefit in patients with DIC, a common finding in serious cases of COVID-19. Nafamostat has been broadly well tolerated in clinical trials in patients with DIC and acute pancreatitis.
TD139Drug
TD139 is a specific inhibitor of galectin-3 which has been investigated in healthy volunteers and patients with IPF. No serious drug related serious adverse events have been reported to date. TD139 had no impact on cardiac, haematological or biochemical measures of safety during trials in humans to date. Beneficial effects on biomarker measures of lung inflammation were observed in patients with IPF. It is the purpose of this investigation to examine the potential for delivery of this inhibitor in pre-ventilator patients hospitalised with COVID-19 to examine whether this may lead to detectable changes in blood biomarkers, reduce viral load and also reduce disease severity such as time to ventilation.
Standard careOther
Patients will receive standard care.
Allogeneic SARS-CoV-2 VSTsBiological
The allogeneic SARS-CoV-2 VSTs are manufactured in a single stage process directly from the starting material procured from suitable post COVID-19 recovered individuals. This is an early dose escalation safety trial phase Ib/IIa interventional clinical trial with SARS-CoV-2 VSTs.
| Study group | Role | What they receive |
|---|---|---|
| Nafamostat | Experimental | It is intended that the licensed dose (0.2mg/kg/hr) in Japan will be used. Patients randomised to Nafamostat will receive a continuous intravenous infusion at 0.2 mg/kg/hr for 7 days. If a participant is discharged from hospital or can no longer receive this treatment, the treatment will be stopped. Receives: Drug: Nafamostat Mesilate |
| TD139 | Experimental | Patients will inhale 5mg x 2 (10 mg) twice daily for the first 48 hrs and then subsequently 5mg x 2 (10 mg) once daily for the remaining 12 days. Unless a participant is discharged from hospital or can no longer use an inhaler - in which case treatment will be stopped at such time.
CE marked inhalers will be provided by the Manufacturer. All patients will receive guidance on how to use the inhaler by an appropriately trained member of the research team. Two individual inhalers will be used by each patient over the course of the 14 day study period (each inhaler will be used by one patient for 7 days) and will be thoroughly cleaned with an antiseptic wipe before and after each use. Receives: Drug: TD139 |
| Standard of Care | Active comparator | Nafamostat and TD139 will be compared to the Standard of Care arm. Receives: Other: Standard care |
| Allogeneic SARS-CoV-2 VSTs | Experimental | This is an early dose escalation safety trial phase Ib/IIa interventional clinical trial with SARS-CoV-2 VSTs. This is a standalone arm of the Define study and will not be compared to any other trial appendices. A dose escalation strategy from 2x104 cells/kg to 2x106 cells/kg (based on standard 75kg weight) will be administered to patients with COVID-19 infection, and patients will be followed up to ensure their safety. Receives: Biological: Allogeneic SARS-CoV-2 VSTs |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of the candidate therapies in COVID-19 patients by measuring physiological changes in the circulatory and respiratory system.
Measure vital signs (blood pressure/heart rate/temperature and respiratory rate)
Measured: Up to 16 days post treatment
The safety of the candidate therapies in COVID-19 patients by recording the number of treatment related adverse events.
Record number of participants With treatment-related adverse events
Measured: Up to 90 days post treatment
Secondary outcomes (11)
Measuring the PK of the proposed trial treatments in COVID-19 patients.
Measure maximum plasma concentration [Cmax] in blood samples.
Measured: 6 months
Measure a change in the expression of key coagulation biomarkers in the blood of COVID-19 patients during and after treatment period.
Change in expression or activity of coagulation markers in serial blood samples taken before, during and after treatment.
Measured: 6 months
Measure a change in the expression of key cytokines in the blood of COVID-19 patients during and after treatment period.
Change in expression or activity of inflammatory cytokines in serial blood samples taken before, during and after treatment.
Measured: 6 months
To evaluate the improvement or deteroriation of patients in each treatment arm.
Record changes in National Early Warning Score (NEWS) 2 score. Scale is from 0-20, with a higher number indicating a higher risk of morbidity.
Measured: 16 days
To evaluate the number of oxygen-free days.
Duration (days) of oxygen use
Measured: 16 days
To evaluate incidence of any form of new ventilation use.
Duration (days) of ventilation
Measured: 16 days
To evaluate ventilator-free days
Duration of ventilation-free days.
- Incidence of any form of new ventilation use and duration (days) of new ventilation use.
Measured: 16 days
Change in the ratio of the oxygen saturation to fraction of inspired oxygen concentration (SpO2/FiO2)
SpO2/FiO2, measured daily from randomisation to Day 15, hospital discharge, or death
Measured: 16 days
To evaluate SARS-CoV-2 viral load.
Qualitative and quantitative polymerase chain reaction (PCR) determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in oropharyngeal/nasal/saliva swab while hospitalised on Days 1, 3, 5, 8, 11, 15.
Measured: 15 days
To evaluate time to discharge
Duration of total hospital stay
- Duration to discharge following treatment
Measured: 16 days
To evaluate the use of renal dialysis or haemofiltration for each treatment arm.
Record requirement for renal dialysis or haemofiltration
Measured: 16 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2020
- Study start3 Jul 2020
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised clinical trial - currently two treatment arms and one standard of care arm. More assets will be added to the protocol as evidence emerges.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Latus Therapeutics, Scottish National Blood Transfusion Service (SNBTS)
- Responsible party
- Sponsor
- Investigators
- Kev Dhaliwal, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04473053
- Sponsor's protocol ID
- AC20063
- Acronym
- DEFINE
- Status last verified
- Jul 2025
- First submitted
- 9 Jul 2020
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The research team actively encourage data sharing to expedite the development of COVID-19 treatments. The study team will provide data to other researchers on request and following the agreement of a data sharing plan. No confidential information regarding participants will be shared.
Publications
Cooper RS, Fraser AR, Smith L, Burgoyne P, Imlach SN, Jarvis LM, Turner DM, Zahra S, Turner ML, Campbell JDM. Rapid GMP-Compliant Expansion of SARS-CoV-2-Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19. Front Immunol. 2021 Jan 8;11:598402. doi: 10.3389/fimmu.2020.598402. eCollection 2020.
PubMed 33488592Gaughan E, Quinn T, Bruce A, Antonelli J, Young V, Mair J, Akram A, Hirani N, Koch O, Mackintosh C, Norrie J, Dear JW, Dhaliwal K. Evaluation of new or repurposed treatments for COVID-19: protocol for the phase Ib/IIa DEFINE trial platform. BMJ Open. 2021 Dec 15;11(12):e054442. doi: 10.1136/bmjopen-2021-054442.
PubMed 34911721Quinn TM, Gaughan EE, Bruce A, Antonelli J, O'Connor R, Li F, McNamara S, Koch O, MacKintosh C, Dockrell D, Walsh T, Blyth KG, Church C, Schwarze J, Boz C, Valanciute A, Burgess M, Emanuel P, Mills B, Rinaldi G, Hardisty G, Mills R, Findlay EG, Jabbal S, Duncan A, Plant S, Marshall ADL, Young I, Russell K, Scholefield E, Nimmo AF, Nazarov IB, Churchill GC, McCullagh JSO, Ebrahimi KH, Ferrett C, Templeton K, Rannard S, Owen A, Moore A, Finlayson K, Shankar-Hari M, Norrie J, Parker RA, Akram AR, Anthony DC, Dear JW, Hirani N, Dhaliwal K. Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics. EBioMedicine. 2022 Feb;76:103856. doi: 10.1016/j.ebiom.2022.103856. Epub 2022 Feb 11.
PubMed 35152152Gaughan EE, Quinn TM, Mills A, Bruce AM, Antonelli J, MacKinnon AC, Aslanis V, Li F, O'Connor R, Boz C, Mills R, Emanuel P, Burgess M, Rinaldi G, Valanciute A, Mills B, Scholefield E, Hardisty G, Findlay EG, Parker RA, Norrie J, Dear JW, Akram AR, Koch O, Templeton K, Dockrell DH, Walsh TS, Partridge S, Humphries D, Wang-Jairaj J, Slack RJ, Schambye H, Phung D, Gravelle L, Lindmark B, Shankar-Hari M, Hirani N, Sethi T, Dhaliwal K. An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis: A Phase Ib/IIa Randomized Controlled Clinical Trial (DEFINE). Am J Respir Crit Care Med. 2023 Jan 15;207(2):138-149. doi: 10.1164/rccm.202203-0477OC.
PubMed 35972987Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DEFINE - Evaluating Therapies for COVID-19
- ClinicalTrials.gov ID
- NCT04473053
- Acronym / sponsor ID
- DEFINE / AC20063
- Conditions
- COVID-19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- University of Oxford, Latus Therapeutics, Scottish National Blood Transfusion Service (SNBTS)
- Study start
- 3 Jul 2020 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 16 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus, SARS CoV2 and is a serious condition with high mortality in hospitalised patients, for which there is no currently approved treatment other than supportive care. Urgent investigation of potential treatments for this condition is required.
This protocol describes an overarching and adaptive trial designed to provide safety, pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biological surrogates of efficacy which may support further development and deployment of candidate therapies in larger scale trials of COVID-19 positive patients receiving normal standard of care.
Given the spectrum of clinical disease, community based infected patients or hospitalised patients can be included. Products requiring parenteral administration will only be investigated in hospitalised patients. Patients will be divided into cohorts, a) community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computed tomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiring assisted ventilation. Participants may be recruited from all three of these cohorts, depending on the experimental therapy, its route of administration and mechanism of action. The relevant cohort(s) for any given therapy will be detailed in the therapy-specific appendix.
Candidate therapies can be added to the protocol and previous candidates removed from further investigation as evidence emerges. The trial will be monitored by an independent Data Monitoring Committee (DMC) to ensure patient safety.
Each candidate cohort will include a small cohort of patients randomised to candidate therapy or existing standard of care management dependent on disease stage at entry. Cohort numbers will be defined in the protocol appendices.
This is a Phase IIa experimental medicine trial and as such formal sample size calculations are not appropriate.
Detailed description
This trial platform aims to support the repurposing of promising therapeutic assets with prior use in humans but without prior information on use in COVID-19, to determine the PK-PD profile of the agent, compared to standard of care supportive therapy, in small cohorts of COVID-19 patients. The results of these studies are intended to provide initial safety, pharmacokinetic and pharmacodynamic data and experimental medicine data to support further evaluation in existing national and international trial networks for candidates demonstrating appropriate impact on the dynamic marker of interest. The key interception is to mitigate the lung damage in patients with COVID-19 that leads to respiratory failure. As such, the assets in this programme will focus on abrogating putative mechanisms implicated in COVID-19 respiratory disease.
Existing approaches in clinical trials involve novel or repurposed antivirals or immunomodulatory approaches involving agents such as corticosteroids, interferon-β or hydroxychloroquine. A major limitation in the design of many early clinical trials is the limited amount of mechanistic data from patients with COVID-19. Mechanisms have been inferred from animal models, related infections or clinical syndromes. These approaches have infrequently translated to human disease. For example, remdesivir efficacy in animal models of Ebola Virus Disease (EVD) did not translate to human disease and hydroxychloroquine antiviral affects in vitro have not translated to humans against other viruses. Some drugs, such as repurposing of the anti-retroviral protease Kaletra, are still being pursued despite uncertain mechanism and despite evidence that this aspartyl protease cannot bind to the cysteine chymotrypsin-like protease that is Kaletra's putative target in COVID-19.
There is a clear and urgent need to pursue experimental medicine studies in humans to establish a solid mechanistic basis for rapid evaluation, including in existing clinical trial platforms against COVID-19 (e.g DoH RECOVERY and NIHR-CLRN industry adopted studies).
The trial will be as flexible as possible to ensure a broad range of patients can be recruited and candidate therapies can be added or removed as evidence emerges. The interim trial results will be monitored by an independent DMC to evaluate any patient safety signals.
As COVID-19 follows a variable clinical path in individual patients, the protocol is designed to enable inclusion of patients across the disease stages. The trial is intended to provide mechanistic data from patients receiving standard of care therapy and from patients treated with the therapy candidates. The study will enable delivery of pharmacokinetic information and effects of standard of care and candidate agents on surrogate biomarkers of the disease process and the specific drug target.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- Randomised clinical trial - currently two treatment arms and one standard of care arm. More assets will be added to the protocol as evidence emerges.
| Arm | Type | Receives |
|---|---|---|
| Nafamostat | Experimental | Drug: Nafamostat MesilateIt is intended that the licensed dose (0.2mg/kg/hr) in Japan will be used. Patients randomised to Nafamostat will receive a continuous intravenous infusion at 0.2 mg/kg/hr for 7 days. If a participant is discharged from hospital or can no longer receive this treatment, the treatment will be stopped. |
| TD139 | Experimental | Drug: TD139Patients will inhale 5mg x 2 (10 mg) twice daily for the first 48 hrs and then subsequently 5mg x 2 (10 mg) once daily for the remaining 12 days. Unless a participant is discharged from hospital or can no longer use an inhaler - in which case treatment will be stopped at such time. CE marked inhalers will be provided by the Manufacturer. All patients will receive guidance on how to use the inhaler by an appropriately trained member of the research team. Two individual inhalers will be used by each patient over the course of the 14 day study period (each inhaler will be used by one patient for 7 days) and will be thoroughly cleaned with an antiseptic wipe before and after each use. |
| Standard of Care | Active comparator | Other: Standard careNafamostat and TD139 will be compared to the Standard of Care arm. |
| Allogeneic SARS-CoV-2 VSTs | Experimental | Biological: Allogeneic SARS-CoV-2 VSTsThis is an early dose escalation safety trial phase Ib/IIa interventional clinical trial with SARS-CoV-2 VSTs. This is a standalone arm of the Define study and will not be compared to any other trial appendices. A dose escalation strategy from 2x104 cells/kg to 2x106 cells/kg (based on standard 75kg weight) will be administered to patients with COVID-19 infection, and patients will be followed up to ensure their safety. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of informed consent from the patient or representative
- Aged at least 16 years
- If the patient is of child bearing potential, the patient, and their partner(s), agree to use medically-accepted double-barrier methods of contraception (eg, barrier methods, including male condom, female condom or diaphragm with spermicidal gel) during the study (if randomised to a treatment arm) and for at least 90 days after termination of study therapy. A vasectomised partner would be considered an appropriate birth control method provided that the partner is the sole male sexual partner and the absence of sperm has been confirmed.
- COVID-19 positive
Key exclusion criteria (15 listed)
- Current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled cardiac disease (NYHA class IV), uncontrolled renal disease (eGFR <30 mL/min/1.73 m2), severe liver dysfunction (ALT/AST >5x ULN) or bone marrow failure (Hb <80 g/L AND ANC<0.5 mm3 AND platelet count <50,000 uL)
- Women who are pregnant or breastfeeding.
- Participation in another clinical trial of an investigational medicinal product (CTIMP)
- Known hypersensitivity to the IMP or excipients (e.g. lactose)
- Pre-existing or Cconcomittant use of off-label treatments for COVID-19 that are not recognised as locally approved standard care.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nafamostat MesilateNafamostat has been shown to have potential antiviral effects against MERS CoV and is thought to possibly inhibit SARS CoV2 infection via inhibition of viral entry due to inhibition of TMPRSS2. In addition, nafamostat has potent anticoagulant properties which may provide benefit in patients with DIC, a common finding in serious cases of COVID-19. Nafamostat has been broadly well tolerated in clinical trials in patients with DIC and acute pancreatitis. | Drug | Nafamostat |
| TD139TD139 is a specific inhibitor of galectin-3 which has been investigated in healthy volunteers and patients with IPF. No serious drug related serious adverse events have been reported to date. TD139 had no impact on cardiac, haematological or biochemical measures of safety during trials in humans to date. Beneficial effects on biomarker measures of lung inflammation were observed in patients with IPF. It is the purpose of this investigation to examine the potential for delivery of this inhibitor in pre-ventilator patients hospitalised with COVID-19 to examine whether this may lead to detectable changes in blood biomarkers, reduce viral load and also reduce disease severity such as time to ventilation. | Drug | TD139 |
| Standard carePatients will receive standard care. | Other | Standard of Care |
| Allogeneic SARS-CoV-2 VSTsThe allogeneic SARS-CoV-2 VSTs are manufactured in a single stage process directly from the starting material procured from suitable post COVID-19 recovered individuals. This is an early dose escalation safety trial phase Ib/IIa interventional clinical trial with SARS-CoV-2 VSTs. | Biological | Allogeneic SARS-CoV-2 VSTs |
Primary outcome
The safety of the candidate therapies in COVID-19 patients by measuring physiological changes in the circulatory and respiratory system.
Time frame: Up to 16 days post treatment
Measure vital signs (blood pressure/heart rate/temperature and respiratory rate)
The safety of the candidate therapies in COVID-19 patients by recording the number of treatment related adverse events.
Time frame: Up to 90 days post treatment
Record number of participants With treatment-related adverse events
11 secondary outcomes
Measuring the PK of the proposed trial treatments in COVID-19 patients.
Time frame: 6 months
Measure a change in the expression of key coagulation biomarkers in the blood of COVID-19 patients during and after treatment period.
Time frame: 6 months
Measure a change in the expression of key cytokines in the blood of COVID-19 patients during and after treatment period.
Time frame: 6 months
To evaluate the improvement or deteroriation of patients in each treatment arm.
Time frame: 16 days
To evaluate the number of oxygen-free days.
Time frame: 16 days
To evaluate incidence of any form of new ventilation use.
Time frame: 16 days
To evaluate ventilator-free days
Time frame: 16 days
Change in the ratio of the oxygen saturation to fraction of inspired oxygen concentration (SpO2/FiO2)
Time frame: 16 days
To evaluate SARS-CoV-2 viral load.
Time frame: 15 days
To evaluate time to discharge
Time frame: 16 days
To evaluate the use of renal dialysis or haemofiltration for each treatment arm.
Time frame: 16 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Background: PubMed 33488592Cooper RS, Fraser AR, Smith L, Burgoyne P, Imlach SN, Jarvis LM, Turner DM, Zahra S, Turner ML, Campbell JDM. Rapid GMP-Compliant Expansion of SARS-CoV-2-Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19. Front Immunol. 2021 Jan 8;11:598402. doi: 10.3389/fimmu.2020.598402. eCollection 2020.
- Background: PubMed 34911721Gaughan E, Quinn T, Bruce A, Antonelli J, Young V, Mair J, Akram A, Hirani N, Koch O, Mackintosh C, Norrie J, Dear JW, Dhaliwal K. Evaluation of new or repurposed treatments for COVID-19: protocol for the phase Ib/IIa DEFINE trial platform. BMJ Open. 2021 Dec 15;11(12):e054442. doi: 10.1136/bmjopen-2021-054442.
- Results publication: PubMed 35152152Quinn TM, Gaughan EE, Bruce A, Antonelli J, O'Connor R, Li F, McNamara S, Koch O, MacKintosh C, Dockrell D, Walsh T, Blyth KG, Church C, Schwarze J, Boz C, Valanciute A, Burgess M, Emanuel P, Mills B, Rinaldi G, Hardisty G, Mills R, Findlay EG, Jabbal S, Duncan A, Plant S, Marshall ADL, Young I, Russell K, Scholefield E, Nimmo AF, Nazarov IB, Churchill GC, McCullagh JSO, Ebrahimi KH, Ferrett C, Templeton K, Rannard S, Owen A, Moore A, Finlayson K, Shankar-Hari M, Norrie J, Parker RA, Akram AR, Anthony DC, Dear JW, Hirani N, Dhaliwal K. Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics. EBioMedicine. 2022 Feb;76:103856. doi: 10.1016/j.ebiom.2022.103856. Epub 2022 Feb 11.
- Results publication: PubMed 35972987Gaughan EE, Quinn TM, Mills A, Bruce AM, Antonelli J, MacKinnon AC, Aslanis V, Li F, O'Connor R, Boz C, Mills R, Emanuel P, Burgess M, Rinaldi G, Valanciute A, Mills B, Scholefield E, Hardisty G, Findlay EG, Parker RA, Norrie J, Dear JW, Akram AR, Koch O, Templeton K, Dockrell DH, Walsh TS, Partridge S, Humphries D, Wang-Jairaj J, Slack RJ, Schambye H, Phung D, Gravelle L, Lindmark B, Shankar-Hari M, Hirani N, Sethi T, Dhaliwal K. An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis: A Phase Ib/IIa Randomized Controlled Clinical Trial (DEFINE). Am J Respir Crit Care Med. 2023 Jan 15;207(2):138-149. doi: 10.1164/rccm.202203-0477OC.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Individual participant dataSharing planned: Yes. The research team actively encourage data sharing to expedite the development of COVID-19 treatments. The study team will provide data to other researchers on request and following the agreement of a data sharing plan. No confidential information regarding participants will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kev Dhaliwal principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nafamostat Mesilate, TD139 and Allogeneic SARS-CoV-2 VSTs in people with COVID-19, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety of the candidate therapies in COVID-19 patients by measuring physiological changes in the circulatory and respiratory system. (time frame: Up to 16 days post treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04473053, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.