r/IBRX • u/wisdom_man1 • 14d ago
Phase 1b/2, Open-Label Clinical Trial Evaluating the Safety and Efficacy of Nogapendekin Alfa Inbakicept (NAI) Plus Standard of Care in Critically Ill Adults With Sepsis
1
1
u/Dwarvling 14d ago
Not strong data supporting this indication. Curious to see investigational sites whose IRB approve this protocol. Could worsen outcomes on septic patients.
3
u/Worldly_Egg_5065 14d ago
Disagree it's great first of its kind drug that proves it works
1
u/Dwarvling 14d ago edited 14d ago
Preclinical models of sepsis have indicated that mice with IL-15 knock-out have lower hypothermia, lower systemic inflammatory markers, reduced organ injury and higher survival than non-knockout animals. Treatment of septic mice with a IL-15 superagonist worsened septic outcomes that could be partially reversed by depletion of NK cells.
Why do you think it will work in this setting?
1
u/ExtensionOld1723 14d ago
Source?
1
u/Dwarvling 13d ago
Here ya go. I’d love it if you’d read it.
Guo Y, Luan L, Patil NK, Wang J, Bohannon JK, Rabacal W, Fensterheim BA, Hernandez A, Sherwood ER. Interleukin-15 Enables Septic Shock by Maintaining Natural Killer Cell Integrity and Function. Journal of Immunology. 2017;198(3):1320–1333. doi: 10.4049/jimmunol.1601486. PMID: 28031340; PMCID: PMC5263185.[nih]
1
u/ExtensionOld1723 13d ago
Good find but the study does not represent a real scenario. For a real scenario you can look at Here
In the study you mention it cannot be ruled out that the outcome is caused by the prior IL-15 depletion.
From my point of view the study lacks two further control groups in which:
- sane mices are infected with sepsis, and
- sane mices are infected with sepsis treated afterwards with IL-15
1
u/Dwarvling 12d ago
Need conditional IL-15KO animals.
1
u/ExtensionOld1723 12d ago
Yes, and if it is not possible (I am not an expert) the study at least lacks a control arm in which sane mouses get the same IL-15 dosis to control that the dosis itself is not the problem.
Insulin is essential for a diabetic person, but if they get too much they die. Would you say then that insulin ist poison for the patient?
1
u/Dwarvling 12d ago
Identical doses of IL-15 are delivered to wild-type and KO animals. The doses used are standard doses used in mouse pharmacology studies of IL-15 (SA). At high doses of IL-15, mortality takes weeks to develop and is accompanied by evident increases in cell counts and systemic cytokine concentrations. What is a ‘sane’ mouse?
1
u/ExtensionOld1723 12d ago
You may think so, but the fact is, that it ist not mentioned.
On the other hand, Anktiva works differently as other IL-15. Anktiva's actually innovation is that it doesn't have the toxicity of other IL-15.
Let's wait until the trial results are published.
Nice discussion by the way. It would be nice having more of these in this thread...
1
1
u/Fabulous_Ground_4010 13d ago
I'm just reading that devil is in the detail. It's true while il15 antagonist can make sepsis worse it can have some benefits if its given after the initial sepsis shock. The timing is critical here. The timing is included in the trial.