About

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 NoWork PackageTitleSummaryDate
1.10COUNTER CovidCOUNTER-COVID midterm recruitment reportThe 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
1.11COUNTER CovidFirst Study Subject Approvals Package, oral studyDetailsAug 2020
1.2COUNTER CovidClose-out reportsClose-out reports for the participating study centres was completed in April 2021Apr 2021
1.3COUNTER CovidDatabase Locked DownThe database for the oral Ph II study was locked down on 5th February 2021Feb 2021
1.4COUNTER CovidStatistical tables, figures and listingsStatistical 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
1.5COUNTER CovidClinical Trial Master FileThe clinical trial master file (TMF) for the oral Ph II clinical study was locked in May 2021May 2021
3.1Manufacturing of Clinical SuppliesMethods for specification in placeAnalytical 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
3.10Manufacturing of Clinical SuppliesOne month solution stability One month stability data for the Laboratory Batch have been submitted as part of the IMPDJan 2021
3.2Manufacturing of Clinical SuppliesLaboratory BatchA Laboratory Batch (Engineering / Stability Batch) has been manufactured and tested to the Drug Product Release SpecificationNov 2020
3.3Manufacturing of Clinical SuppliesProduct Contact Part Compatibility reportThe 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
3.4Manufacturing of Clinical SuppliesTechnology Transfer DocumentPrior 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
3.5Manufacturing of Clinical SuppliesFilter Validation reportBubble 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
3.6Manufacturing of Clinical SuppliesSterilisation reportMedia Fill Certificate - COC2088 confirms that the KABS facility is appropriate for aseptic
fill and sterile filtration
Jan 2021
3.7Manufacturing of Clinical SuppliesQP Release of Clinical Trial SuppliesThe QP Certificate of Release (Conformance) has been issuedFeb 2021
3.8Manufacturing of Clinical SuppliesCMC section of IMPDA 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 approvalJan 2021
3.9Manufacturing of Clinical SuppliesDispatch of clinical trial supplies to the clinical trial sitesClinical supplies are in place for use at clinical sites according to the protocolFeb 2021
5.1INVENT CovidProtocol of Phase II IV studyThe protocol is available to view at https://www.clinicaltrialsregister.euDec 2020
5.10INVENT CovidMedical Monitoring PlanThe medical monitoring plan was finalised on 28 Jan 2021, prior to the first-patient-first-visit in the study.Feb 2021
5.12INVENT CovidDSMB CharterThe DSMB charter was included as part of the CTA submitted in Dec 2020.Jan 2021
5.13INVENT CovidData Management and validation planSept 2020
5.2INVENT CovidInvestigator Brochure (IB)The IB has been completed and will be submitted to regulatory authorities for reviewNov 2020
5.3INVENT CovidInvestigational Medicinal product Dossier (IMPD)The IMPD has been completed and will be submitted to regulatory authorities as part of the CTADec 2020
5.4INVENT CovidClinical Trial Application (CTA)The CTA has been submitted for review. Once approved information contained will be available at https://www.clinicaltrialsregister.eu/Dec 2020
5.5INVENT CovidFirst Study subject approvals package for iv studyCompetent authority decision is registered on the EU Clinical
Trials Register (EudraCT number 2020-005447-23)
Feb 2021
5.6INVENT CovidEthics Submission of Phase II IV studyThe CTA was submitted in Dec 2020. Confirmation of ethics approval will be made available on https://www.clinicaltrialsregister.eu/Dec 2020
5.7INVENT CovidEthics ApprovalThe independent ethics committee approved the study protocol on 22 January 2021Jan 2021
5.8INVENT CovidSite Audit reportsA 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
5.9INVENT CovidMedical Monitoring PlanThe monitoring plan described the monitoring of subjects at all sites participating in the INVENT COVID trial. A summary is available on requestMay 2021
7.1CommunicationsA Face to Face consortium kick-off meetingThe project kick-off meeting occurred on 13th July 2020. Due to the COVID pandemic, this took place by videoconferenceJul 2020
7.2CommunicationsAn infrastructure for secure communication between consortium membersA sharepoint collaboration site has been established and it's use endorsed by the General AssemblyJul 2020
7.3CommunicationsA consortium brand to be used consistently in al internal and external communicationsA project logo has been designed and utilised internally and externally on communication materialAug 2020
7.4CommunicationsWebsite and social media presencehttps://impentri.exvastat.comAug 2020
8.1EthicsEthics approval for COUNTER COVID studyThe CMMO in the Netherlands approved the study protocol and patient consent letter, prior to the study start. FURTHER INFORMATIONOct 2020
8.3EthicsEthics Requirement number 4All required import documentation was received and drug product was delivered to AMCJan 2021
8.4EthicsEthics Requirement no 5The 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
1.7COUNTER CovidPeer 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
1.8COUNTER CovidPresentation of "Oral imatinib in severe COVID-19" study resultsPresentations 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
4.1PharmacokineticsValidated covariat PK modelThe full details of the validated covariate PK model was published in CPTPharmacometrics & Systems
Pharmacology in Oct 2021
Oct 2021
5.11INVENT CovidSafety Database Set UpThe safety database for the clinical study has been establishedFeb 2021
6.2CommercialisationCosted Clinical Development PlanA costed clinical development plan has been crated and will be included in the business planSept 2021
6.3CommercialisationDraft TPP, Protocols and IB for Ph III studiesThe 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
6.4CommercialisationBusiness PlanA business plan has been developed and this is available on request from admin@exvastat.comSept 2021
6.5CommercialisationInvestment pitch slidesA set of investment pitch slides have been developed. these are available on request from admin@exvastat.comSept 2021
1.1COUNTER CovidMonthly DSMB reportsDSMB reports from meetings 1 and 2 in April and May 2020 submittedMarch 2021
1.6COUNTER CovidOral 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
4.2PharmacokineticsOral Phase II pharmacokinetic reportResults of the oral phase II PK report (model building only) was published in CPT:Pharmacometrics & Systems Pharmacology in 2021Jan 2022