Revisions for CIMAvax-EGF®-post-COVID19 convalescent with respiratory disorders-adults-Phase II (CORVAXCIM) | Registro Público Cubano de Ensayos Clínicos

Comparing two revisions:

--- 6 December 2021 - 8:25pm by CIM
+++ 19 July 2023 - 3:27pm by Gladys
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-Grade 3, 4 or 5 toxicity attributable to the therapeutic vaccine CIMAvax-EGF® (Occurrence of adverse events (AE) with severity grade 3 (severe), 4 (serious that threat or incapacitating) or 5 (serious that produces death) with a Causality relationship attributable to the product (definitive, very probable, probable, possible)). Measurement time: 6 months.
+Response to treatment (It will measure through the variation of forced vital capacity (FVC) in the categories favorable or unfavorable. It will be considered Favorable response when FVC does not vary or is reduced by less than 10% in patients with pulmonary fibrosis and does not vary or is reduced by less than 5% in patients with another respiratory disorder with respect to the initial measurement. Unfavorable response: when FVC is reduced more than 10% with respect to the initial measurement in patients with pulmonary fibrosis, and more than 5% in patients with another respiratory disorder). Measurement time: days 63 and 182.
 . Outcome of the AE (1. Reversible effect, 2. Effect 3. Death 4. Irreversible loss of patient monitoring). Measurement time: 6 months.
 Effect:
-. Response to treatment (It will measure through the variation of forced vital capacity (FVC) in the categories favorable or unfavorable. It will be consider favorable response when FVC does not vary or is reduced by less than 10% in patients with pulmonary fibrosis and does not vary or is reduced by less than 5% in patients with another respiratory disorder with respect to the initial measurement. Unfavorable response: when FVC is reduced more than 10% with respect to the initial measurement in patients with pulmonary fibrosis, and more than 5% in patients with another respiratory disorder). Measurement time: days 63 and 182.
+. Maximum expiratory volume-VEM (It is the fraction of the forced vital capacity that can expire in the first second in a forced expiration after a maximum inspiration, observed value in ml). Measurement time: days 0, 63 and 182.
-. Maximum expiratory volume-VEM (It is the fraction of the forced vital capacity that can expire in the first second in a forced expiration after a maximum inspiration, observed value in ml). Measurement time: days 0, 63 and 182.
+. Number of lesions (number of lesions that the patient presents at each moment of evaluation, measured by CT). Measurement time: days 0, 63 and 182.
-. Number of lesions (number of lesions that the patient presents at each moment of evaluation, measured by CT). Measurement time: days 0, 63 and 182.
+. Type of lesion (nonspecific pulmonary fibrosis, tarnished virio pattern, reticulo-nodular pattern, or other). Measurement time: days 0, 63 and 182.
-. Type of lesion (nonspecific pulmonary fibrosis, tarnished virio pattern, reticulo-nodular pattern, or other). Measurement time: days 0, 63 and 182.
+. Lesion location: In the right lung (Upper lobe: anterior, posterior or apical, Middle lobe: medial or lateral, or Lower lobe: apical, anterior, posterior, internal, external). In the left lung (Upper lobe: apical posterior, anterior, superior lingular, inferior lingular, Lower lobe: apical, anterior, posterior, external. Measurement time: days 0, 63 and 182.
-. Lesion location: In the right lung (Upper lobe: anterior, posterior or apical, Middle lobe: medial or lateral, or Lower lobe: apical, anterior, posterior, internal, external). In the left lung (Upper lobe: apical posterior, anterior, superior lingular, inferior lingular, Lower lobe: apical, anterior, posterior, external. Measurement time: days 0, 63 and 182.
+. Extension of the lesion: Area of the lesion in cm2. Measurement time: days 0, 63 and 182.
-. Extension of the lesion: Area of the lesion in cm2. Measurement time: days 0, 63 and 182.
+. Modification of the measurable lesion according to extension: (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
-. Modification of the measurable lesion according to extension: (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
+. Number of affected segments for non-measurable lesions (number of affected segments). Measurement time: days 0, 63 and 182.
-. Number of affected segments for non-measurable lesions (number of affected segments). Measurement time: days 0, 63 and 182.
+. Variation of the non-measurable lesion (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
-. Variation of the non-measurable lesion (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
+. Evolution of pulmonary fibrosis (increase, persistence, or reduction of the tomographic signs of fibrosis, as well as modification of its extension in the tissue). Measurement time: days 0, 63 and 182.
-. Evolution of pulmonary fibrosis (increase, persistence, or reduction of the tomographic signs of fibrosis, as well as modification of its extension in the tissue). Measurement time: days 0, 63 and 182.
 Immunology response:
 . Serum EGF concentration: The EGF concentration in the blood of the patients will be determined. Measurement time: on days 0, 63 and 182.
 . Anti-EGF antibody titers: The antibody titers in response to short-term vaccination will be determined in each patient and it will be determined if it is ≥ 1: 4000. Measurement time: on days 0, 63 and 182.
 . Anti-RBD antibody titers: The antibody titers in response to vaccination will be determined in each patient. Measurement time: on days 0, 63 and 182.
 . Concentration of C - reactive protein (laboratory values). Measurement time: days 0, 63 and 182.
 . Neutrophil/lymphocyte ratio (The neutrophil / lymphocyte ratio will be determined from the blood count values). Measurement time: days 0, 63 and 182.
 . Platelet/lymphocyte ratio (The platelet / lymphocyte ratio will be determined from the values of the blood count). Measurement time: days 0, 63 and 182.
 . Absolute count and frequency of CD4 + T cells (The amount and percentage of CD4 + T cells in the blood will be determined). Measurement time: days 0, 63 and 182.
 . Absolute count and frequency of CD8 + T cells (The amount and percentage of CD8 + T cells in the blood will be determined). Measurement time: days 0, 63 and 182.
 . Frequency of CD8 + CD28- T cells (The percentage of CD8 + CD208- T cells in the blood will be determined). Measurement time: days 0, 63 and 182.
 . CD4 / CD8 index (The CD4 / CD8 index in blood will be determined). Measurement time: days 0, 63 and 182.
 CIMAvax-EGF group (Experimental). The patients will receive 8 administrations of the product. Every administrationwill have a dose of 2.4 mg of the active principle of the therapeutic vaccine CIMAvax-EGF® (rhEGF-rP64k conjugate) in 1.2 mL of the injection (vaccine in aqueous phase plus Montanide ISA 51 VG) intramuscularly. The total dose will be divided into 4 subdoses, equivalent to 0.6 mg of EGF at each site of inoculation (both deltoid regions and both glutes). During the induction phase they will receive 4 administrations, one every 14 days. They will then receive 4 doses during the maintenance phase, one dose every 28 days, until 6 months of treatment are completed.
-Control group: Conventional treatment for this type of postCOVID-19 disorder in Cuba for the duration of the study. This treatment may include bronchodilator drugs, steroids, oxygen therapy, hypotensive drugs in case of pulmonary hypertension and respiratory rehabilitation, among others considered by the specialized personnel in the care of these patients.
+Patients in this group will additionally receive the best supportive therapy available, which may include: steroids (depending on the type of respiratory disorder and medical criteria, without exceeding a total daily dose of 60 mg / day for 14 days and / or weekly gradual reduction), bronchodilators, antibiotics in case of infection, hypotensive drugs in case of pulmonary hypertension, medicines for heart failure in case of cor pulmonale, oxygen therapy and / or pulmonary rehabilitation.
-In each group the patients will be divided into two strata:
-Stratum 1: Patients with pulmonary fibrosis
+Control group: Patients in this group will receive the best supportive therapy available, which may include: steroids (depending on the type of respiratory disorder and medical criteria, without exceeding a total daily dose of 60 mg / day for 14 days and / or weekly gradual reduction), bronchodilators, antibiotics in case of infection, hypotensive drugs in case of pulmonary hypertension, medicines for heart failure in case of cor pulmonale, oxygen therapy and / or pulmonary rehabilitation.
-Stratum 2: Patients with any other respiratory disorder without pulmonary fibrosis
+In each group the patients will be divided into two subgroups:
+Subgroup 1: Patients with post-COVID-19 pulmonary fibrosis
+Subgroup 2: Patients with another post-COVID-19 respiratory disorder not pulmonary fibrosis
 . Subject of any sex and age greater than or equal to 18 years.
 . Subjects for whom at least 14 days have elapsed from discharge from the post-COVID-19 patient care service or referral of the specialized consultation.
-. Subject that in the pre-inclusion checkup they have: hemoglobin ≥ 9 g/L, leukocytes ≥ 3.4x109 L, absolute neutrophil count ≥ 1.5 x 109 L.
+. Patients with respiratory clinical manifestations and deterioration of respiratory function due to spirometric or radiological functional pattern.
-. Liver and kidney function tests in normal ranges, or out of range without clinical relevance.
+. Subject that in the pre-inclusion checkup they have: hemoglobin ≥ 9 g/L, leukocytes ≥ 3.4x109 L, absolute neutrophil count ≥ 1.5 x 109 L.
-. Functional status according to Karnofsky ≥ 40%.
+. Liver and kidney function tests in normal ranges.
-. Pregnancy, postpartum and breastfeeding.
+. Patients with pre-existing lung disorders (including pulmonary fibrosis, COPD, severe asthma, lung cancer, etc).
-. Subjects of childbearing age who are not using an adequate method of contraception prior to their inclusion in the study (intrauterine devices, hormonal contraceptives, barrier methods or tubal ligation). In the case of males (vasectomy, use of condoms).
+. Patients with confirmed severe or life-limiting chronic disease, or a history of angioedema prior to COVID-19 infection.
-. Known hypersensitivity to any component of the CIMAvax-EGF formulation.
+. Pregnancy or lactation period.
-. Patient receiving other investigational product.
+. Subjects of childbearing age who are not using an adequate method of contraception prior to their inclusion in the study.
-. Obvious mental incapacity to give consent and act accordingly with the study.
+. Subject that they are receiving another product under investigation.
+. Known hypersensitivity to any of the components of the formulation under study.
+. Obvious mental incapacity to issue consent and act accordingly with the study.
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Current revision:

CIMAvax-EGF®-post-COVID19 convalescent with respiratory disorders-adults-Phase II (CORVAXCIM)

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Acronym of Public Title:

CORVAXCIM

Scientific title:

Safety and effect of CIMAvax-EGF® in convalescent patients from SARS-CoV-2 infection with respiratory disorders. Phase II (COVID-19)

Acronym of Scientific Title:

CORVAXCIM

Secondary indentifying numbers:

In process

Issuing authority of the secondary identifying numbers:

Center of Molecular Immunology (CIM)

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

In process

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Soraida

Midle name:

Candida

Last name:

Acosta Brooks

Medical Specialty :

Second Degree Specialist of Internal Medicine

Affiliation:

Saturnino Lora´s Hospital

Postal address:

Avenida de Los Libertadores s/n, entre 4ta y 6ta, Reparto Suenno

City:

Santiago de Cuba

Country:

Cuba

Zip Code:

90100

Telephone:

+53-22645447

Email address:

soraidac@infomed.sld.cu

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Not applicable

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

25/12/2021

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Respiratory disorders in convalescent patients from SARS-CoV-2 infection

Health condition(s) code:

Coronavirus Infections

SARS Virus

Coronaviridae Infections

Betacoronavirus

Pulmonary Fibrosis

Lung Diseases

Respiratory Tract Diseases

Health condition keyword:

COVID-19

SARS-CoV2

Intervention(s):

CIMAvax-EGF group (Experimental). The patients will receive 8 administrations of the product. Every administrationwill have a dose of 2.4 mg of the active principle of the therapeutic vaccine CIMAvax-EGF® (rhEGF-rP64k conjugate) in 1.2 mL of the injection (vaccine in aqueous phase plus Montanide ISA 51 VG) intramuscularly. The total dose will be divided into 4 subdoses, equivalent to 0.6 mg of EGF at each site of inoculation (both deltoid regions and both glutes). During the induction phase they will receive 4 administrations, one every 14 days. They will then receive 4 doses during the maintenance phase, one dose every 28 days, until 6 months of treatment are completed. Patients in this group will additionally receive the best supportive therapy available, which may include: steroids (depending on the type of respiratory disorder and medical criteria, without exceeding a total daily dose of 60 mg / day for 14 days and / or weekly gradual reduction), bronchodilators, antibiotics in case of infection, hypotensive drugs in case of pulmonary hypertension, medicines for heart failure in case of cor pulmonale, oxygen therapy and / or pulmonary rehabilitation. Control group: Patients in this group will receive the best supportive therapy available, which may include: steroids (depending on the type of respiratory disorder and medical criteria, without exceeding a total daily dose of 60 mg / day for 14 days and / or weekly gradual reduction), bronchodilators, antibiotics in case of infection, hypotensive drugs in case of pulmonary hypertension, medicines for heart failure in case of cor pulmonale, oxygen therapy and / or pulmonary rehabilitation. In each group the patients will be divided into two subgroups: Subgroup 1: Patients with post-COVID-19 pulmonary fibrosis Subgroup 2: Patients with another post-COVID-19 respiratory disorder not pulmonary fibrosis

Intervention code:

Immunotherapy, Active

Epidermal Growth Factor

Injections, Intramuscular

Intervention keyword:

CIMAvax-EGF

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Response to treatment (It will measure through the variation of forced vital capacity (FVC) in the categories favorable or unfavorable. It will be considered Favorable response when FVC does not vary or is reduced by less than 10% in patients with pulmonary fibrosis and does not vary or is reduced by less than 5% in patients with another respiratory disorder with respect to the initial measurement. Unfavorable response: when FVC is reduced more than 10% with respect to the initial measurement in patients with pulmonary fibrosis, and more than 5% in patients with another respiratory disorder). Measurement time: days 63 and 182.

Key secondary outcomes:

Safety: 1. Occurrence of any AE (Yes, No). Measurement time: 6 months. 2. Adverse event description (Name of the adverse event). Measurement time: 6 months. 3. Duration of the adverse event (Difference between the start date and the stop of the event). Measurement time: 6 months. 4. Intensity of AE (1. Light, 2. Moderate 3. Severe, 5. Very severe 5. Death, according to Common Toxicity Criteria (CTCAE) version 5.0). Measurement time: 6 months. 5. Causality relationship (.Definitive, 2.Very likely, 3.Likely, 4.Possible, 5.Unlikely, 6.Unrelated, 7.Unknown). Measurement time: 6 months. 6. Gravity (Seriousness) of AE (Critical event / No serious. Serious event (seriously) be considered as causing the death of the patient, life-threatening, results in hospitalization or prolongation of existing hospitalization, causes disability / persistent or significant disability, birth defects or congenital anomalies or an important medical event that according to medical judgment, could endanger the health of the patient or may require medical or surgical intervention to prevent the occurrence of any of the previously listed outcomes). Measurement time: 6 months. 7. Attitude towards drug (1. No change 2. Dose reduction 3. Temporary discontinuation of treatment. 4. Definitive Treatment discontinuation). Measurement time: 6 months. 8. Outcome of the AE (1. Reversible effect, 2. Effect 3. Death 4. Irreversible loss of patient monitoring). Measurement time: 6 months. Effect: 1. Maximum expiratory volume-VEM (It is the fraction of the forced vital capacity that can expire in the first second in a forced expiration after a maximum inspiration, observed value in ml). Measurement time: days 0, 63 and 182. 2. Number of lesions (number of lesions that the patient presents at each moment of evaluation, measured by CT). Measurement time: days 0, 63 and 182. 3. Type of lesion (nonspecific pulmonary fibrosis, tarnished virio pattern, reticulo-nodular pattern, or other). Measurement time: days 0, 63 and 182. 4. Lesion location: In the right lung (Upper lobe: anterior, posterior or apical, Middle lobe: medial or lateral, or Lower lobe: apical, anterior, posterior, internal, external). In the left lung (Upper lobe: apical posterior, anterior, superior lingular, inferior lingular, Lower lobe: apical, anterior, posterior, external. Measurement time: days 0, 63 and 182. 5. Extension of the lesion: Area of the lesion in cm2. Measurement time: days 0, 63 and 182. 6. Modification of the measurable lesion according to extension: (increase, no variation or reduction). Measurement time: days 0, 63 and 182. 7. Number of affected segments for non-measurable lesions (number of affected segments). Measurement time: days 0, 63 and 182. 8. Variation of the non-measurable lesion (increase, no variation or reduction). Measurement time: days 0, 63 and 182. 9. Evolution of pulmonary fibrosis (increase, persistence, or reduction of the tomographic signs of fibrosis, as well as modification of its extension in the tissue). Measurement time: days 0, 63 and 182. Immunology response: 10. Serum EGF concentration: The EGF concentration in the blood of the patients will be determined. Measurement time: on days 0, 63 and 182. 11. Anti-EGF antibody titers: The antibody titers in response to short-term vaccination will be determined in each patient and it will be determined if it is ≥ 1: 4000. Measurement time: on days 0, 63 and 182. 12. Anti-RBD antibody titers: The antibody titers in response to vaccination will be determined in each patient. Measurement time: on days 0, 63 and 182. 13. Concentration of C - reactive protein (laboratory values). Measurement time: days 0, 63 and 182. 14. Neutrophil/lymphocyte ratio (The neutrophil / lymphocyte ratio will be determined from the blood count values). Measurement time: days 0, 63 and 182. 15. Platelet/lymphocyte ratio (The platelet / lymphocyte ratio will be determined from the values of the blood count). Measurement time: days 0, 63 and 182. 16. Absolute count and frequency of CD4 + T cells (The amount and percentage of CD4 + T cells in the blood will be determined). Measurement time: days 0, 63 and 182. 17. Absolute count and frequency of CD8 + T cells (The amount and percentage of CD8 + T cells in the blood will be determined). Measurement time: days 0, 63 and 182. 18. Frequency of CD8 + CD28- T cells (The percentage of CD8 + CD208- T cells in the blood will be determined). Measurement time: days 0, 63 and 182. 19. CD4 / CD8 index (The CD4 / CD8 index in blood will be determined). Measurement time: days 0, 63 and 182.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

None

Inclusion criteria:

1. Willingness of the patient by signing the informed consent. 2. Subject of any sex and age greater than or equal to 18 years. 3. Subjects for whom at least 14 days have elapsed from discharge from the post-COVID-19 patient care service or referral of the specialized consultation. 4. Patients with respiratory clinical manifestations and deterioration of respiratory function due to spirometric or radiological functional pattern. 5. Subject that in the pre-inclusion checkup they have: hemoglobin ≥ 9 g/L, leukocytes ≥ 3.4x109 L, absolute neutrophil count ≥ 1.5 x 109 L. 6. Liver and kidney function tests in normal ranges.

Exclusion criteria:

1. Patients with pre-existing lung disorders (including pulmonary fibrosis, COPD, severe asthma, lung cancer, etc). 2. Patients with confirmed severe or life-limiting chronic disease, or a history of angioedema prior to COVID-19 infection. 3. Pregnancy or lactation period. 4. Subjects of childbearing age who are not using an adequate method of contraception prior to their inclusion in the study. 5. Subject that they are receiving another product under investigation. 6. Known hypersensitivity to any of the components of the formulation under study. 7. Obvious mental incapacity to issue consent and act accordingly with the study.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

Target sample size:

135

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Soraida

Middle Name:

Candida

Last Name:

Acosta Brooks

Specialty:

Second Degree Specialist of Internal Medicine

Affiliation:

Saturnino Lora´s Hospital

Postal Address:

Avenida de Los Libertadores s/n, entre 4ta y 6ta, Reparto Suenno

City:

Santiago de Cuba

Country:

Cuba

Zip Code:

90100

Telephone:

+53-22645447

Email :

soraidac@infomed.sld.cu

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Soraida

Middle Name:

Candida

Last Name:

Acosta Brooks

Specialty:

Second Degree Specialist of Internal Medicine

Affiliation:

Saturnino Lora´s Hospital

Postal Address:

Avenida de Los Libertadores s/n, entre 4ta y 6ta, Reparto Suenno

City:

Santiago de Cuba

Country:

Cuba

Zip Code:

90100

Telephone:

+53-22645447

Email :

soraidac@infomed.sld.cu

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

Saturnino Lora´s Hospital

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

18/05/2021

Postal address of Ethic Committee :

Avenida de Los Libertadores s/n, entre 4ta y 6ta, Reparto Suenno ZC 90100. Santiago de Cuba. Cuba

Telephone:

+53-622277; +53-626571 ext 1600

Email:

rafel.surez@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Study completion date:

30/01/2023

Date of available results:

30/04/2023

Date of first publication:

30/06/2023

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000375

Date of Registration in Primary Registry:

18/06/2021

Record Verification Date:

2021/12/06

Next update date:

2022/12/06

Link to the spanish version:

Click here

Registered Trials

Registration process

CIMAvax-EGF®-post-COVID19 convalescent with respiratory disorders-adults-Phase II (CORVAXCIM)

About the RPCEC

Useful resources