COVID-19
Conditions
Keywords
SARS-CoV-2 Infection, COVID-19 Pandemic, 2019 Novel Coronavirus Disease, Thymic peptides, Thymus gland, Peptides, Honduras, Coronavirus Disease 2019, Coronavirus Disease-19, COVID-19 Virus Infection, 2019-nCoV Disease, 2019-nCoV Infection
Brief summary
This is a single-arm, open-label, phase II clinical study to evaluate the safety and efficacy of thymic peptides in the treatment of hospitalized COVID-19 patients in Honduras.
Detailed description
This study was approved and registered by the Dirección General de Vigilancia del Marco Normativo de la Secretaría de Salud de Honduras (General Directorate for Regulatory Framework Surveillance of the Ministry of Health of Honduras) the eight of February of 2021; enrollment began tenth of February of 2021. The study will analyze 23 clinical parameters, 9 laboratory studies besides complete blood count, chest radiography, time to response, adverse clinical outcomes, and hospital length of stay in 22 participants treated with a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment. A participant-level comparison based on registry data from Hospital de Santa Bárbara Integrado will be performed after propensity score matching. The Generic Assessment of Side Effects in Clinical Trials (GASE) will be applied in addition to monitoring of treatment-emergent adverse events.
Interventions
BIOLOGICALThymic peptides
250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.
Sponsors
Pontificia Universidad Catolica de Chile
Universidad Católica de Honduras
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A participant-level comparison based on registry data from the Hospital de Santa Bárbara Integrado will be performed after propensity score matching.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed case of COVID-19 by viral nucleic acid (RNA) detection, viral antigen detection, or detection of antibodies to the virus. * Participants that require hospitalization under Honduran Ministry of Health Guidelines for Clinical Management of COVID-19 Adult Patients: Stage IIb, defined as a patient with or without risk factors that presents with warning signs (shortness of breath, tachypnea), and altered inflammatory parameters. * Participants that present with at least one of the following: oxygen saturation level below 94 percent; complete blood count showing lymphopenia, neutrophilia, or both; positive C-reactive protein; chest radiography or CT scan with ground-glass opacities. * Male or female at least 21 years old.
Exclusion criteria
* COVID-19 patients that do not require hospitalization under Honduran Ministry of Health Guidelines for Clinical Management of COVID-19 Adult Patients: phase IA (asymptomatic), phase IB (mild symptoms without risk factors), or phase IC (mild symptoms with risk factors). * Participants currently in other clinical trials evaluating experimental drugs. * Known history of allergic reactions to thymic peptides or calf thymus acid lysate derivatives. * Organ transplant recipients. * Women who are pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Participant Recovery | During hospitalization for up to 20 days. | Measured in days to clinical recovery that will be defined as the first day, during the 20 days after enrollment, on which a patient met the criteria for category 1, 2, or 3 on the eight-category ordinal scale. The categories are as follows: 1, not hospitalized and no limitations of activities; 2, not hospitalized, with limitation of activities, home oxygen requirement, or both; 3, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4, hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to Covid-19 or to other medical conditions); 5, hospitalized, requiring any supplemental oxygen; 6, hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7, hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8, death. |
| Number of Participants With Treatment Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 5.0 | Up to 20 days | Number of participants who experience adverse events ≥ Grade 3, as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). |
| Number of Participants With Treatment Related Side Effects as Assessed by the General Assessment of Side Effects | Up to 20 days | Number of participants who experience severe side effects as defined by the General Assessment of Side Effects (GASE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Died by Day 20 | Up to 20 days | Number of participants that died due to any reason by day 20. |
Countries
Honduras
Participant flow
Pre-assignment details
22 participants were enrolled in the intervention group. A participant-level comparison based on a control group by propensity score matching from registry data was performed. This accounts for the 22 patients in the arm of the historic control group. ClinicalTrials.gov Identifier: NCT04771013 MedRxiv: A nonrandomized phase 2 trial of oral thymic peptides in hospitalized patients with Covid-19. doi: https://doi.org/10.1101/2021.12.05.21267318
Participants by arm
| Arm | Count |
|---|---|
| Daily Oral Dose of Thymic Peptides Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge.
Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach. | 22 |
| Historic Control Group A participant-level comparison based on a control group by propensity score matching from registry data was performed.
For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020.
Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin). | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 5 |
| Overall Study | Referred to another hospital before day 20 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Daily Oral Dose of Thymic Peptides | Historic Control Group | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 16 | 57 years STANDARD_DEVIATION 17 | 54 years STANDARD_DEVIATION 16 |
| Age, Customized ≤60 years | 15 Participants | 12 Participants | 27 Participants |
| Age, Customized 61-64 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Customized ≥ 65 years | 5 Participants | 7 Participants | 12 Participants |
| Coexisting conditions-Chronic obstructive pulmonary disease | 1 Participants | 1 Participants | 2 Participants |
| Coexisting conditions-Diabetes | 11 Participants | 3 Participants | 14 Participants |
| Coexisting conditions-Heart Failure | 0 Participants | 1 Participants | 1 Participants |
| Coexisting conditions-Hypertension | 7 Participants | 9 Participants | 16 Participants |
| Coexisting conditions-Obesity | 2 Participants | 4 Participants | 6 Participants |
| Coexisting conditions-Organ damage (other than lung) | 12 Participants | 15 Participants | 27 Participants |
| Comorbidities | 2 Comorbidities STANDARD_DEVIATION 1 | 2 Comorbidities STANDARD_DEVIATION 2 | 2 Comorbidities STANDARD_DEVIATION 1 |
| Heart rate distribution 111-130 beats/min | 2 Participants | 2 Participants | 4 Participants |
| Heart rate distribution 51-90 beats/min | 14 Participants | 10 Participants | 24 Participants |
| Heart rate distribution 91-110 beats/min | 6 Participants | 10 Participants | 16 Participants |
| Median no. of days since symptom onset | 11.5 days | 10 days | 10.5 days |
| Oxygen saturation distribution ≤91% | 19 Participants | 19 Participants | 38 Participants |
| Oxygen saturation distribution 92-93% | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Mestizo | 22 Participants | 22 Participants | 44 Participants |
| Region of Enrollment Honduras | 22 participants | 22 participants | 44 participants |
| Respiratory rate distribution 21-24 breaths/min | 2 Participants | 3 Participants | 5 Participants |
| Respiratory rate distribution ≥ 25 breaths/min | 20 Participants | 19 Participants | 39 Participants |
| SARS-CoV-2 positive test result | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
| Systolic blood pressure distribution 90-219 mmHg | 22 Participants | 22 Participants | 44 Participants |
| Temperature distribution 35.6-37.9 °C | 19 Participants | 19 Participants | 38 Participants |
| Temperature distribution 38-39 °C | 3 Participants | 2 Participants | 5 Participants |
| Temperature distribution ≥39.1 °C | 0 Participants | 1 Participants | 1 Participants |
| WHO Clinical Progression Score of 5 at hospitalization | 22 Participants | 22 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 5 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 5 / 22 |
Outcome results
Primary
Number of Participants With Treatment Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 5.0
Number of participants who experience adverse events ≥ Grade 3, as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).
Time frame: Up to 20 days
Population: Only Treatment Related Adverse Event data related to mortality was collected from the Historic Control population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Oral Dose of Thymic Peptides | Number of Participants With Treatment Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 5.0 | 0 Participants |
| Historic Control Group | Number of Participants With Treatment Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 5.0 | 5 Participants |
Primary
Number of Participants With Treatment Related Side Effects as Assessed by the General Assessment of Side Effects
Number of participants who experience severe side effects as defined by the General Assessment of Side Effects (GASE).
Time frame: Up to 20 days
Population: Treatment Related Side Effects data not collected from the Historic Control population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Oral Dose of Thymic Peptides | Number of Participants With Treatment Related Side Effects as Assessed by the General Assessment of Side Effects | 0 Participants |
Primary
Time to Participant Recovery
Measured in days to clinical recovery that will be defined as the first day, during the 20 days after enrollment, on which a patient met the criteria for category 1, 2, or 3 on the eight-category ordinal scale. The categories are as follows: 1, not hospitalized and no limitations of activities; 2, not hospitalized, with limitation of activities, home oxygen requirement, or both; 3, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4, hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to Covid-19 or to other medical conditions); 5, hospitalized, requiring any supplemental oxygen; 6, hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7, hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8, death.
Time frame: During hospitalization for up to 20 days.
Population: Analyses were performed according to the intention-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daily Oral Dose of Thymic Peptides | Time to Participant Recovery | 6 days |
| Historic Control Group | Time to Participant Recovery | 12 days |
Secondary
Number of Participants That Died by Day 20
Number of participants that died due to any reason by day 20.
Time frame: Up to 20 days
Population: The analysis assessed the number of patients that died in each arm by day 20.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Oral Dose of Thymic Peptides | Number of Participants That Died by Day 20 | 0 Participants |
| Historic Control Group | Number of Participants That Died by Day 20 | 5 Participants |