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Vaccination of Ex-acute COVID-19 Patients With Fibrosing Lung Syndrome at Discharge (COVINVAC)

Primary Purpose

Pulmonary Fibrosis, Covid19

Status

Unknown status

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

IN01 vaccine

About this trial

This is an interventional treatment trial for Pulmonary Fibrosis focused on measuring EGF, Fibrosis secondary to Covid19 infection, IN01 vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
Age 18 years or older.
Patients with positive RT-PCR or IGm/IGG blood test for SARS-CoV-2 prior to the inclusion in the study.
Patients that have pneumonia associated to SARS-CoV-s infection prior to randomization.
Patients having respiratory dysfunction after SARS-CoV-2 infection and abnormal CT chest imaging.
Patients previously under high flow nasal cannula or non-invasive ventilation, or supplementary oxygen, during hospitalization for COVID-19.
Increased EGF level (more than 200 picogram/ml).
Negative serum pregnancy test at screening for women of childbearing potential.
Highly effective contraception for both male and female subjects throughout the study and for at least 3 months after last IMP treatment administration if the risk of conception exists.

Exclusion Criteria:

Patients with previous IPF, Autoimmune disease or connective tissue diseases (CTD).
Known of previous clinically significant pulmonary abnormalities that may interfere with the measurement of study variables in the opinion of the investigator as ILD, or chronic respiratory failure.
Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) in the context of a clinical study.
Included a physician's decision that involvement in the trial was not in the patient's best interest.
Presence of any condition that would not allow the protocol to be followed safely.
Any mental health condition, that may interfere in the normal development of the study according to physician criteria.
Known hypersensitivity to the trial medication or its components
Other disease that may interfere with testing procedures or may put the patient at risk when participating in this trial in the judgment of the Investigator.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Women of childbearing potential* not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to and 3 months after experimental treatment administration. A list of contraception methods meeting these criteria is provided in the patient information.
Active alcohol or drug abuse in the opinion of the investigator.
Any other reason that the investigator deems to be incompatible with the patient'sparticipation in study.

Sites / Locations

Hospital El Pilar

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Experimental

Control

Arm Description

The investigational medical product, the IN01 vaccine, will be administered in two phases to those patients in the experimental arm: the induction phase and the maintenance phase. During the induction phase IN01 vaccine will be administered on day 1 and will be repeated on Day 14, Day 28, Day 42 and day 56. During the maintenance phase, the vaccination will be administered every 2 months with the same dosage and administration mode as during induction.

The patients enrolled in the control arm of the study will receive standard of care.

Outcomes

Primary Outcome Measures

Safety (Frequency/severity of AEs)

Frequency and severity of AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria and hematological alterations that are clinical relevant under physician criteria. Data will be presented as number of AEs classified by severity.

Secondary Outcome Measures

Oxygen saturation

blood oxygen levels will be measured by a pulse oximeter

Quality of life (QoL)

St George QoL questionnaire: Disease-specific questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.

Fibrotic pulmonary extension (measured as the size of the lesions)

High-resolution CT to follow fibrotic pattern reviewed by a central radiologist

Full Information

NCT ID

NCT04537130

First Posted

September 2, 2020

Last Updated

September 22, 2020

Sponsor

Instituto Oncológico Dr Rosell

Collaborators

IN3BIO, PANGAEA

1. Study Identification

Unique Protocol Identification Number

NCT04537130

Brief Title

Vaccination of Ex-acute COVID-19 Patients With Fibrosing Lung Syndrome at Discharge

Acronym

COVINVAC

Official Title

Phase Ib Controlled Exploratory Trial for Treatment of Fibrosing Interstitial Lung Disease Patients Secondary to SARS-CoV-2 Infection With IN01 Vaccine (COVINVAC)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2020 (Anticipated)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

June 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Instituto Oncológico Dr Rosell

Collaborators

IN3BIO, PANGAEA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Methodology: This is a controlled, randomized, multicenter open-label Phase Ib clinical exploratory trial in patients with fibrosing interstitial lung disease secondary to SARS-CoV-2 infection. Patients who give informed consent will be screened for enrolment in the study. Patients that meet the eligibility criteria will be enrolled and randomly allocated in the control arm (best standard of care) or the experimental arm (best standard of care plus IN01 vaccination). The patients enrolled in the control arm of the study will receive standard of care. The primary endpoint is safety, measured by the Frequency and severity of AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria. Biochemical and blood count alterations will be also monitored. Safety will be defined based on the frequency and severity of adverse events (AEs) throughout the patient's participation in the study comparing between control and experimental arms. Efficacy will be measured as function of the annual rate of decline in the Forced Vital Capacity (FVC) at 1 year after patient inclusion in the study and the blood oxygen saturation levels at days 1, 14 (w2), d 28 (w4), 42 (w6) and 92 (w12); week 24, week 36 and week 52. High-resolution Computed Tomography (CT) scans will be taken at at baseline and weeks, 12, 24, and 52 to evaluate the resolution of the fibrosing interstitial lung disease. A translational substudy will be included. Objectives: Primary Objective ● To evaluate the safety and tolerability of IN01 vaccine in diagnosed ex-COVID-19 patients that develop fibrotic lung syndrome after infection. Secondary Objectives To evaluate the effect of IN01 vaccine on Oxygen saturation, pulmonary function, quality of life and fibrosing status in ex-COVID-19 patients that developed fibrosing lung disease after infection. To assess biomarkers and molecular markers related to the IN01 vaccine mechanism of action.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Fibrosis, Covid19

Keywords

EGF, Fibrosis secondary to Covid19 infection, IN01 vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

The trial will enroll 40 patients to be treated with either standard of care (control arm) or IN01 vaccine (experimental arm). Patients will be randomized in a 5:3 ratio to achieve 25 patients allocated in the experimental vs 15 patients in the control arm.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

No Intervention

Arm Description

The patients enrolled in the control arm of the study will receive standard of care.

Intervention Type

Biological

Intervention Name(s)

IN01 vaccine

Intervention Description

INO1 vaccine is a biological compound comprising generated and purified from recombinant bacteria culture that contains a protein consisting of EGF-4-EGF portion and the Cholera Toxin B-Subunit Domain G33D sequence (CTB-G33D) separated by 4 amino acids and 14 amino acids respectively glycine/serine-rich linkers. IN01 is a recombinant growth factor fusion molecule which, once injected into the patient, stimulates the immune system to produce polyclonal anti-Epidermal Growth Factor (anti-EGF) neutralizing antibodies. This vaccine-led active immunisation is a new approach to target the growth factor pathways allowing for combinations with other small molecule inhibitors in order to obtain a sustained efficacy with an acceptable toxicity. The vaccine inhibits binding of circulating Epidermal Growth Factor (EGF) to its receptor, EGF-R to block downstream activation of cell signaling pathways contributing to tumor growth or other pathophysiologies such as fibrosis.

Primary Outcome Measure Information:

Title

Safety (Frequency/severity of AEs)

Description

Time Frame

Through study completion, average 1 year

Secondary Outcome Measure Information:

Title

Oxygen saturation

Description

blood oxygen levels will be measured by a pulse oximeter

Time Frame

baseline and days 1, 14 (w2), 28 (w4), 42 (w6) and 92 (w12); week 24, week 36 and week 52

Title

Quality of life (QoL)

Description

Time Frame

baseline and weeks 2, 12, 24, 36 and 52

Title

Fibrotic pulmonary extension (measured as the size of the lesions)

Description

High-resolution CT to follow fibrotic pattern reviewed by a central radiologist

Time Frame

baseline and weeks, 12, 24, and 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities. Age 18 years or older. Patients with positive RT-PCR or IGm/IGG blood test for SARS-CoV-2 prior to the inclusion in the study. Patients that have pneumonia associated to SARS-CoV-s infection prior to randomization. Patients having respiratory dysfunction after SARS-CoV-2 infection and abnormal CT chest imaging. Patients previously under high flow nasal cannula or non-invasive ventilation, or supplementary oxygen, during hospitalization for COVID-19. Increased EGF level (more than 200 picogram/ml). Negative serum pregnancy test at screening for women of childbearing potential. Highly effective contraception for both male and female subjects throughout the study and for at least 3 months after last IMP treatment administration if the risk of conception exists. Exclusion Criteria: Patients with previous IPF, Autoimmune disease or connective tissue diseases (CTD). Known of previous clinically significant pulmonary abnormalities that may interfere with the measurement of study variables in the opinion of the investigator as ILD, or chronic respiratory failure. Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) in the context of a clinical study. Included a physician's decision that involvement in the trial was not in the patient's best interest. Presence of any condition that would not allow the protocol to be followed safely. Any mental health condition, that may interfere in the normal development of the study according to physician criteria. Known hypersensitivity to the trial medication or its components Other disease that may interfere with testing procedures or may put the patient at risk when participating in this trial in the judgment of the Investigator. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Women of childbearing potential* not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to and 3 months after experimental treatment administration. A list of contraception methods meeting these criteria is provided in the patient information. Active alcohol or drug abuse in the opinion of the investigator. Any other reason that the investigator deems to be incompatible with the patient'sparticipation in study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Federico Nepote

Phone

934344412

investigacion@mfar.net

First Name & Middle Initial & Last Name or Official Title & Degree

Verónica Roca

Phone

934344412

investigacion@mfar.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pablo Rubinstein, MD, MSc, PhD

Organizational Affiliation

Hospital El Pilar

Official's Role

Study Chair

Facility Information:

Facility Name

Hospital El Pilar

City

Barcelona

ZIP/Postal Code

08006

Country

Spain

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Investigator Selected by Sponsor

Phone

934344412

investigacion@mfar.net

First Name & Middle Initial & Last Name & Degree

Investigator Selected by Sponsor

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Vaccination of Ex-acute COVID-19 Patients With Fibrosing Lung Syndrome at Discharge

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