ApTOLL for the Treatment of COVID-19

Study Overview
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Brief Summary
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There is a clear and urgent medical need of developing new medicinal products for COVID-19 since there are poor pharmacological tools to block the progression of patients to cytokine storm syndrome (CSS). To this aim, this Phase Ib clinical study (APTACOVID) pretends to determine whether ApTOLL, in combination with the standard of care, is safe and shows any biological effect) in those patients infected with SARS-CoV-2 who are not developed CSS yet.

Official Title
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A Double Blind, Placebo-Controlled, Randomized, Phase Ib Clinical Study of ApTOLL for the Treatment of COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: ApTOLL
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women with age ≥18 and ≤85 years. In case of women of childbearing potential (WOCBP), they should confirm menstrual period and a negative highly sensitive urine or serum pregnancy test to be included. Laboratory-confirmed SARS-CoV-2 infection. Informed consent obtained . Hypoxia (SpO2<95%). Documented lung opacities/infiltrates. Confirmed hyperinflammation. Exclusion Criteria: Onset of symptoms of COVID-19 >14 days. Pregnant or nursing (lactating) women. Hospitalized >10 days for COVID-19. Need of high concentration non-rebreather mask, high-flow nasal cannula , non-invasive mechanical ventilation or invasive mechanical ventilation. Systolic blood pressure < 90 mmHg. Serious concomitant illness. Recent treatment with cell-depleting therapies. Enrolled in another clinical trial. Severe renal dysfunction. In the opinion of the investigator, unable to comply with the requirements to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Nine COVID-19 patients (three from each treatment-group) treated with saline intravenous infusion | Other: Saline<br>* Saline for intravenous infusion<br>|
| Experimental: Dose 1<br>Seven COVID-19 patients treated with ApTOLL (0.05mg/kg) intravenous infusion | Drug: ApTOLL<br>* ApTOLL is an aptamer (DNA single strain) designed to block TLR4 (toll-like receptor 4)<br>|
| Experimental: Dose 2<br>Seven COVID-19 patients treated with ApTOLL (0.1mg/kg) intravenous infusion | Drug: ApTOLL<br>* ApTOLL is an aptamer (DNA single strain) designed to block TLR4 (toll-like receptor 4)<br>|
| Experimental: Dose 3<br>Seven COVID-19 patients treated with ApTOLL (0.2mg/kg) intravenous infusion | Drug: ApTOLL<br>* ApTOLL is an aptamer (DNA single strain) designed to block TLR4 (toll-like receptor 4)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Death | Number of dead patients at the end of the study | From dosing to day 28 after administration | 
| Incidence of Adverse Events as assessed by MedDRA | Adverse events that occur during the study | From dosing to day 28 after administration | 
| Number of patients with treatment-related alterations coagulation parameters | Protrombine Time (PT) and activated Partial Tromboplastine Time (aPTT) | From dosing to day 28 after administration | 
| Number of patients with treatment-related alterations Complement Factors | Complement activation determined in blood | From dosing to day 28 after administration |