About
IMPENTRI IMI2 CONSORTIUM
Objectives
The Impentri IMI2 project involves the repurposing and rapid development of an existing therapy, imatinib, as a new and improved therapeutic approach for acute respiratory distress syndrome (ARDS) resulting from SARS-CoV-2 infection. More details about the technology can be found here
The accumulation of fluid in the lungs is a significant feature of the pathology in patients with severe Covid-19 infection and contributes to difficulty in breathing and in some cases death. The project aims to target the root cause of the condition, decrease mortality and improve the quality of life of the patient.
This clinical stage project aims to investigate the use of imatinib in two pilot clinical studies for the treatment of Covid-19 ARDS. The first trial, a Phase II trial of orally administered imatinib in COVID-19 infected and hospitalised patients before they develop ARDS has now completed (EUDRACT no. 2020-001236-10). The second trial is a randomized, double-blind, Phase II study to evaluate the efficacy, safety and pharmacokinetics of intravenously administered imatinib (Impentri™) in patients with Covid-19 associated ARDS. This trial was approved in January 2021 and recruitment commenced in March 2021. (EUDRACT no. 2020-005447-23).
Following demonstration of safety and efficacy in Covid-19 ARDS, Impentri™ will be made available for compassionate use, and it is hoped, will be progressed to Phase III studies and subsequent regulatory approval and commercialization.
The Consortium
The teams in the Netherlands at VU and AMC in Amsterdam, will lead the Phase II clinical research program in Covid-19 patients at risk of ARDS using oral imatinib, and then in ICU patients with ARDS using IV imatinib (Impentri™). Development and supply of the IV formulation of imatinib will be conducted by KABS Pharmaceutical Services in Canada, with clinical operational support from Simbec-Orion, based in France. The overall project coordination will be managed by Exvastat Ltd.
Data
In accordance with policies on the sharing of digital research data arising from projects funded by IMI, the IMPENTRI project will make available all appropriate data within 30 days of its creation.
For further information on any of these items, please contact admin@exvastat.com
| Deliverable No | Work Package | Title | Summary | Date |
|---|---|---|---|---|
| 1.10 | COUNTER Covid | COUNTER-COVID midterm recruitment report | The DSMB conducted a safety assessment at their 3rd meeting on 22 Oct, based on data for 115 patients who had completed 28 day follow-up. They recommended that the study be continued. 50% recruitment to the study (193 patients) was achieved on 29th October. | Jan 2021 |
| 1.11 | COUNTER Covid | First Study Subject Approvals Package, oral study | Details | Aug 2020 |
| 1.2 | COUNTER Covid | Close-out reports | Close-out reports for the participating study centres was completed in April 2021 | Apr 2021 |
| 1.3 | COUNTER Covid | Database Locked Down | The database for the oral Ph II study was locked down on 5th February 2021 | Feb 2021 |
| 1.4 | COUNTER Covid | Statistical tables, figures and listings | Statistical Tables, figures and listings for the oral Phase II clinical study were completed in April 2021. These have been included in the clinical studypublication and it’s supplemental information. | Apr 2021 |
| 1.5 | COUNTER Covid | Clinical Trial Master File | The clinical trial master file (TMF) for the oral Ph II clinical study was locked in May 2021 | May 2021 |
| 3.1 | Manufacturing of Clinical Supplies | Methods for specification in place | Analytical methodology for the drug product formulation testing (for both release and stability studies) are in place. The drug product specification is in place prior to regulatory acceptance | Nov 2020 |
| 3.10 | Manufacturing of Clinical Supplies | One month solution stability | One month stability data for the Laboratory Batch have been submitted as part of the IMPD | Jan 2021 |
| 3.2 | Manufacturing of Clinical Supplies | Laboratory Batch | A Laboratory Batch (Engineering / Stability Batch) has been manufactured and tested to the Drug Product Release Specification | Nov 2020 |
| 3.3 | Manufacturing of Clinical Supplies | Product Contact Part Compatibility report | The compatibility of imatinib drug product solution with product contact parts has been tested and confirmed acceptable. No evidence of adsorption or degradation was noted | Jan 2021 |
| 3.4 | Manufacturing of Clinical Supplies | Technology Transfer Document | Prior to commencing manufacture of Clinical Trial supplies, there has been a review of all supporting documentation and justifications. This “readiness to manufacture” assessment has been collated as a Technology Transfer Document | Jan 2021 |
| 3.5 | Manufacturing of Clinical Supplies | Filter Validation report | Bubble point testing was performed during the manufacturing process and documented within the Executed Master Batch Records to confirm that sterilisation by filtration had been achieved | Jan 2021 |
| 3.6 | Manufacturing of Clinical Supplies | Sterilisation report | Media Fill Certificate - COC2088 confirms that the KABS facility is appropriate for aseptic fill and sterile filtration | Jan 2021 |
| 3.7 | Manufacturing of Clinical Supplies | QP Release of Clinical Trial Supplies | The QP Certificate of Release (Conformance) has been issued | Feb 2021 |
| 3.8 | Manufacturing of Clinical Supplies | CMC section of IMPD | A full Drug Product section (Module 3) of the IMPD has been prepared and has been submitted as part of the CTA to the relevant regulatory authority for review and approval | Jan 2021 |
| 3.9 | Manufacturing of Clinical Supplies | Dispatch of clinical trial supplies to the clinical trial sites | Clinical supplies are in place for use at clinical sites according to the protocol | Feb 2021 |
| 5.1 | INVENT Covid | Protocol of Phase II IV study | The protocol is available to view at https://www.clinicaltrialsregister.eu | Dec 2020 |
| 5.10 | INVENT Covid | Medical Monitoring Plan | The medical monitoring plan was finalised on 28 Jan 2021, prior to the first-patient-first-visit in the study. | Feb 2021 |
| 5.12 | INVENT Covid | DSMB Charter | The DSMB charter was included as part of the CTA submitted in Dec 2020. | Jan 2021 |
| 5.13 | INVENT Covid | Data Management and validation plan | Sept 2020 | |
| 5.2 | INVENT Covid | Investigator Brochure (IB) | The IB has been completed and will be submitted to regulatory authorities for review | Nov 2020 |
| 5.3 | INVENT Covid | Investigational Medicinal product Dossier (IMPD) | The IMPD has been completed and will be submitted to regulatory authorities as part of the CTA | Dec 2020 |
| 5.4 | INVENT Covid | Clinical Trial Application (CTA) | The CTA has been submitted for review. Once approved information contained will be available at https://www.clinicaltrialsregister.eu/ | Dec 2020 |
| 5.5 | INVENT Covid | First Study subject approvals package for iv study | Competent authority decision is registered on the EU Clinical Trials Register (EudraCT number 2020-005447-23) | Feb 2021 |
| 5.6 | INVENT Covid | Ethics Submission of Phase II IV study | The CTA was submitted in Dec 2020. Confirmation of ethics approval will be made available on https://www.clinicaltrialsregister.eu/ | Dec 2020 |
| 5.7 | INVENT Covid | Ethics Approval | The independent ethics committee approved the study protocol on 22 January 2021 | Jan 2021 |
| 5.8 | INVENT Covid | Site Audit reports | A Research Statement/Certificate of suitability for the Research Institution (VGO) has been completed for the sites at AMC and OLVG confirming that the sites are suitable to conduct the research. | Jan 2021 |
| 5.9 | INVENT Covid | Medical Monitoring Plan | The monitoring plan described the monitoring of subjects at all sites participating in the INVENT COVID trial. A summary is available on request | May 2021 |
| 7.1 | Communications | A Face to Face consortium kick-off meeting | The project kick-off meeting occurred on 13th July 2020. Due to the COVID pandemic, this took place by videoconference | Jul 2020 |
| 7.2 | Communications | An infrastructure for secure communication between consortium members | A sharepoint collaboration site has been established and it's use endorsed by the General Assembly | Jul 2020 |
| 7.3 | Communications | A consortium brand to be used consistently in al internal and external communications | A project logo has been designed and utilised internally and externally on communication material | Aug 2020 |
| 7.4 | Communications | Website and social media presence | https://impentri.exvastat.com | Aug 2020 |
| 8.1 | Ethics | Ethics approval for COUNTER COVID study | The CMMO in the Netherlands approved the study protocol and patient consent letter, prior to the study start. FURTHER INFORMATION | Oct 2020 |
| 8.3 | Ethics | Ethics Requirement number 4 | All required import documentation was received and drug product was delivered to AMC | Jan 2021 |
| 8.4 | Ethics | Ethics Requirement no 5 | The final version of the protocol, the registration number of the clinical trial, the ethics committee approval and the patient informed consent form have been provided to IMI JU. | Mar 2021 |
| 1.7 | COUNTER Covid | Peer reviewed publication reporting findings from the the oral Phase II clinical study | A peer reviewed publication reporting findings from the oral Phase II clinical study has been published in The Lancet Respiratory Medicine, June 17, 2021 | June 2021 |
| 1.8 | COUNTER Covid | Presentation of "Oral imatinib in severe COVID-19" study results | Presentations of the results of the “oral imatinib in severe COVID-19” study were made at ESC, ERS and Thomas Petty Lingo Lung Conferences in August and September 2021 | Sept 2021 |
| 4.1 | Pharmacokinetics | Validated covariat PK model | The full details of the validated covariate PK model was published in CPTPharmacometrics & Systems Pharmacology in Oct 2021 | Oct 2021 |
| 5.11 | INVENT Covid | Safety Database Set Up | The safety database for the clinical study has been established | Feb 2021 |
| 6.2 | Commercialisation | Costed Clinical Development Plan | A costed clinical development plan has been crated and will be included in the business plan | Sept 2021 |
| 6.3 | Commercialisation | Draft TPP, Protocols and IB for Ph III studies | The draft TPP for Impentri™ treatment of ARDS, including COVID-19 ARDS, the Impentri™ IB and the REMAP-CAP core protocol have been prepared and can be requested from admin@exvastat.com | Sept 2021 |
| 6.4 | Commercialisation | Business Plan | A business plan has been developed and this is available on request from admin@exvastat.com | Sept 2021 |
| 6.5 | Commercialisation | Investment pitch slides | A set of investment pitch slides have been developed. these are available on request from admin@exvastat.com | Sept 2021 |
| 1.1 | COUNTER Covid | Monthly DSMB reports | DSMB reports from meetings 1 and 2 in April and May 2020 submitted | March 2021 |
| 1.6 | COUNTER Covid | Oral Phase II clinical study report on "Oral Imatinib in severe COVID-19" | The Clinical Study Report for the Oral Phase II study was completed in the form of the clinical study publications | June 2021 |
| 4.2 | Pharmacokinetics | Oral Phase II pharmacokinetic report | Results of the oral phase II PK report (model building only) was published in CPT:Pharmacometrics & Systems Pharmacology in 2021 | Jan 2022 |
| 2.1 | Pathophysiology | Pathophysiology report & Manuscript | See manuscript | Oct 2022 |
| 4.3 | Pharmacokinetics | Validated continuous biomarker models | See Manuscript | July 2022 |
| 4.4 | Pharmacokinetics | Validated exposure-response and toxicity models | See Manuscript | July 2022 |
| 5.14 | INVENT Covid | Monitoring Visit Reports | Monitoring visit reports for the five clinical sites were conducted periodically between March 2021 and April 2022 | Oct 2022 |
| 5.16 | INVENT Covid | Close-out Visit reports | Close-out visits for the clinical sites were completed by 11 July 2022 | Oct 2022 |
| 5.17 | INVENT Covid | TFLs | Final TFLs were presented to Exvastat and trial sponsor, VUmc in Aug 2022 | Oct 2022 |
| 5.22 | INVENT Covid | Presentation of "IV imatinib in severe COVID-19" | See presentation | Oct 2022 |