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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
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.
Hospital El Pilar
Barcelona, Spain
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.
Time frame: Through study completion, average 1 year
Oxygen saturation
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
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.
Time frame: baseline and weeks 2, 12, 24, 36 and 52
Fibrotic pulmonary extension (measured as the size of the lesions)
High-resolution CT to follow fibrotic pattern reviewed by a central radiologist
Time frame: baseline and weeks, 12, 24, and 52
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