Janssen&Janssen schreef op 9 augustus 2021 21:07:
Om het nog even goed en duidelijk op het netvlies te zetten voor iedereen, hierbij nog eem intressante link + bijlage over de lopende Basel studie. Hier bij zit ook het 57 pagina's tellende studie protocol van de trial.
Ik heb er voor het gemak enkele belangrijke stukken uitgehaald
trialsjournal.biomedcentral.com/artic...Pharming Biotechnologies B.V. was involved in the design of the study at an initial stage and in the organization of the study in Brazil and Mexico. The funders will have no role in collection, management, analysis and interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication.
1.6 Data Safety Monitoring Committee
We do not expect serious adverse events related to conestat alfa not mentioned in this document or not previously described in clinical studies of conestat alfa (see current Investigator’s Brochure). As the frequency of comorbidities in the patient population under study is significant and clinical complications.are common in patients with COVID-19 infection, serious adverse events are possible in this setting.
Hence, we will establish periodic interim safety review meetings (ISRM) by an independent committee.
This Data Safety Monitoring Board (DSMB) will be responsible for safeguarding the interests of the study participants by monitoring adverse events and in particular serious adverse events. The DSMB may also consider factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the patients or the ethics of the study. An independent statistician from the CTU will provide the DSMB with the pertinent safety data. The DSMB’s responsibility, roles and procedures will be specified in a DSMB-Charter. A first ISRM will take place after inclusion of 30 patients. The advice(s) of the (DSMB) will only be sent to the Sponsor of the study. Should the Sponsor decide not to fully implement this advice, the Sponsor will send the advice to the competent authorities and (C)EC, as appropriate, including a note to substantiate why (part of) the advice of the DSMB will not be followed.
2.3 Competent Ethics Committee (CEC)
The principal investigator and the responsible investigator at each site ensures that approval from an appropriately constituted CEC will be sought for the clinical study prior to commencement of the study.
No changes will be made to the protocol without prior CEC approval, except where necessary to
eliminate apparent immediate hazards to study participants. Reporting duties: Written progress reports will be sent to the CEC annually, or more frequently if requested by the CEC. All Suspected Unexpected Serious Adverse Reactions will be reported within 7 (leading to death) or 15 (others) days to the CEC.
All SAEs leading to death will be reported within 7 days to the CEC. Unanticipated problems involving risks to humans will be reported immediately to the CEC.
Premature study end or interruption of the study is reported within 15 days. The regular end of the study
is reported to the CEC within 90 days, the final study report shall be submitted within one year after study end. Amendments are reported according to chapter 2.10.
2.9 Early termination of the study
The Sponsor-Investigator may terminate the study prematurely according to certain circumstances, for example:
? ethical concerns,
? insufficient participant recruitment,
? when the safety of the participants is doubtful or at risk, respectively,
? alterations in accepted clinical practice that make the continuation of a clinical trial unwise,
? early evidence of benefit or harm of the experimental intervention
A DSMB will continuously monitor patients’ safety. The DSMB will independently judge and recommend on the need to halt enrolment for further evaluations or to terminate the trial based on information regarding safety.
3.7 Risks / Benefits
Despite strong reasons for a benefit of conestat alfa in the setting of hyperinflammation, it is unclear if participants in the current study will receive any immediate benefit from treatment with conestat alfa. However, the knowledge gained from this study may help to better understand the pathophysiology of ALI and hyperinflammation in SARS-CoV-2 and related CoV infections. In addition, this trial may serve as pilot study for future conestat alfa studies in patients with severe infections characterized by hyperinflammation and subsequent tissue damage.
11.4.4 Interim analyses
Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels ap = 0.0221. Based on the results of an interim analysis the sample size can be adjusted (Lehmacher, Wassmer, 1999). There are no prespecified futility margins, but the DSMB can recommend stopping the study in the case of insufficient interim results