Clinical trial NCT04537130: Vaccination of Ex-acute COVID-19 Patients With Fibrosing Lung Syndrome at Discharge
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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pulmonary Fibrosis
Covid19
Keywords: EGF
Fibrosis secondary to Covid19 infection
IN01 vaccine
Lead sponsor: Instituto Oncológico Dr Rosell
Sponsor class: OTHER
Collaborators: name: IN3BIO
name: PANGAEA
First posted: 2020-09-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
2. Age 18 years or older.
3. Patients with positive RT-PCR or IGm/IGG blood test for SARS-CoV-2 prior to the inclusion in the study.
4. Patients that have pneumonia associated to SARS-CoV-s infection prior to randomization.
5. Patients having respiratory dysfunction after SARS-CoV-2 infection and abnormal CT chest imaging.
6. Patients previously under high flow nasal cannula or non-invasive ventilation, or supplementary oxygen, during hospitalization for COVID-19.
7. Increased EGF level (more than 200 picogram/ml).
8. Negative serum pregnancy test at screening for women of childbearing potential.
9. 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:

1. Patients with previous IPF, Autoimmune disease or connective tissue diseases (CTD).
2. 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.
3. Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) in the context of a clinical study.
4. Included a physician's decision that involvement in the trial was not in the patient's best interest.
5. Presence of any condition that would not allow the protocol to be followed safely.
6. Any mental health condition, that may interfere in the normal development of the study according to physician criteria.
7. Known hypersensitivity to the trial medication or its components
8. 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.
9. 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.
10. Active alcohol or drug abuse in the opinion of the investigator.
11. Any other reason that the investigator deems to be incompatible with the patient'sparticipation in study.

Primary outcomes:
measure: Safety (Frequency/severity of AEs)
timeFrame: Through study completion, average 1 year
Secondary outcomes:
measure: Oxygen saturation
timeFrame: baseline and days 1, 14 (w2), 28 (w4), 42 (w6) and 92 (w12); week 24, week 36 and week 52
measure: Quality of life (QoL)
timeFrame: baseline and weeks 2, 12, 24, 36 and 52
measure: Fibrotic pulmonary extension (measured as the size of the lesions)
timeFrame: baseline and weeks, 12, 24, and 52
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital El Pilar
Study officials:
affiliation: Hospital El Pilar
name: Pablo Rubinstein, MD, MSc, PhD
role: STUDY_CHAIR
References: