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

• Register: RPCEC
• Last refreshed on: 21 June 2021
• Main ID: RPCEC00000375
• Date of registration: 18/06/2021
• Prospective Registration: Yes
• Primary sponsor: Center of Molecular Immunology (CIM)
• Public title: CIMAvax-EGF®-post-COVID19 convalescent with respiratory disorders-adults-Phase II (CORVAXCIM)
• Scientific title: Safety and effect of CIMAvax-EGF® in convalescent patients from SARS-CoV-2 infection with respiratory disorders. Phase II (COVID-19) - CORVAXCIM
• Date of first enrolment: 25/06/2021
• Target sample size: 100
• Recruitment status: Pending
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000375-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Open. Control group: Active. Assignment: Parallel. Purpose: Treatment
• Phase: 2

Countries of recruitment

Cuba

Contacts

• Name: Soraida Candida Acosta Brooks
• Affiliation: Saturnino Lora´s Hospital

• Name: Soraida Candida Acosta Brooks
• Affiliation: Saturnino Lora´s Hospital

Key inclusion & exclusion criteria

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. 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.
5. Liver and kidney function tests in normal ranges, or out of range without clinical relevance.
6. Functional status according to Karnofsky = 40%.

Exclusion criteria: 1. Pregnancy, postpartum and breastfeeding.
2. 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).
3. Known hypersensitivity to any component of the CIMAvax-EGF formulation.
4. Patient receiving other investigational product.
5. Obvious mental incapacity to give consent and act accordingly with the study.


Age minimum: 18 years
Age maximum: None
Gender: Male/Female

Health Condition(s) or Problem(s) studied

Betacoronavirus

Coronaviridae Infections

Coronavirus Infections

COVID-19

Lung Diseases

Pulmonary Fibrosis

Respiratory disorders in convalescent patients from SARS-CoV-2 infection
COVID-19
SARS-CoV2

Respiratory Tract Diseases

SARS Virus

SARS-CoV2

Intervention(s)

CIMAvax-EGF

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.
In each group the patients will be divided into two strata:
Stratum 1: Patients with pulmonary fibrosis
Stratum 2: Patients with any other respiratory disorder without pulmonary fibrosis

Epidermal Growth Factor

Immunotherapy, Active

Injections, Intramuscular

Primary Outcome(s)

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.

Secondary Outcome(s)

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. 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.
2. 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.
3. 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.
4. Type of lesion (nonspecific pulmonary fibrosis, tarnished virio pattern, reticulo-nodular pattern, or other). Measurement time: days 0, 63 and 182.
5. 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.
6. Extension of the lesion: Area of the lesion in cm2. Measurement time: days 0, 63 and 182.
7. Modification of the measurable lesion according to extension: (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
8. Number of affected segments for non-measurable lesions (number of affected segments). Measurement time: days 0, 63 and 182.
9. Variation of the non-measurable lesion (increase, no variation or reduction). Measurement time: days 0, 63 and 182.
10. 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:
11. Serum EGF concentration: The EGF concentration in the blood of the patients will be determined. Measurement time: on days 0, 63 and 182.
12. 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.
13. 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.
14. Concentration of C - reactive protein (laboratory values). Measurement time: days 0, 63 and 182.
15. Neutrophil/lymphocyte ratio (The neutrophil / lymphocyte ratio will be determined from the blood count values). Measurement time: days 0, 63 and 182.
16. Platelet/lymphocyte ratio (The platelet / lymphocyte ratio will be determined from the values of the blood count). Measurement time: days 0, 63 and 182.
17. 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.
18. 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.
19. 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.
20. CD4 / CD8 index (The CD4 / CD8 index in blood will be determined). Measurement time: days 0, 63 and 182.

Secondary ID(s)

In process

Source(s) of Monetary Support

Center of Molecular Immunology (CIM)

Secondary Sponsor(s)

Not applicable

Ethics review

Status: Approved
Approval date: 18/05/2021
Contact:

[e-mail]

[e-mail]

[phone]; [phone] ext 1600

[e-mail]

Results

• Date Posted: 30/10/2022
• Date Completed: 30/10/2022