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.
Biological: IN01 vaccine
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.
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.
Hospital El Pilar
Barcelona, Spain
Investigator: Investigator Selected by Sponsor
Contact: 934344412
investigacion@mfar.net
Investigator: Investigator Selected by Sponsor
Federico Nepote
934344412
investigacion@mfar.net
Verónica Roca
934344412
investigacion@mfar.net
Pablo Rubinstein, MD, MSc, PhD, Study Chair
Hospital El Pilar