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Posted On: 06/12/2022 11:42:12 AM
Post# of 148899
The dosing issue can be addressed simply by closing the loop more frequently and dosing based on the feedback.
Step 1: Obtain pre-treatment cT1 and PDFF levels.
Step 2: Based on those numbers, classify NAS level.
Step 3: Start dosing 525mg LL weekly for 4 weeks
Step 4: At 1 month, repeat cT1 and PDFF. Calculate absolute change from baseline by determining the difference.
Step 5: if the change in cT1 < -20 msec OR PDFF < - 7, maintain 525 LL; if ct1 > -20 msec OR > -7, lower dosing to 350 mg LL
(What I mean by "less than <", I mean that the dosing was sufficient enough as to remove enough fibrotic scar tissue or steatosis that the measurement was more negative than -20 or -7). (The opposite holds for "greater than >"
.
Step 6: Continue either same dose of 525mg or new dose of 350mg LL for the 2nd month.
Step 7: At end of 2nd month, again, repeat cT1 and PDFF and again calculate the change from previous month. Again, go back to Step 5.
Step 8. Repeat for 4 months or 16 weeks.
The idea is try to maximize the amount of scar tissue lost, change in cT1 or amount of PDFF lost, steatosis, by quantifying it monthly and reducing the LL dosage until the best results are elicited.
There will likely be other biomarkers which may be used, other than cT1 / PDFF, possibly Receptor Occupancy which could be measured on each physician visit to optimize treatment.
A phase 3 trial like this could be easily constructed.
Step 1: Obtain pre-treatment cT1 and PDFF levels.
Step 2: Based on those numbers, classify NAS level.
Step 3: Start dosing 525mg LL weekly for 4 weeks
Step 4: At 1 month, repeat cT1 and PDFF. Calculate absolute change from baseline by determining the difference.
Step 5: if the change in cT1 < -20 msec OR PDFF < - 7, maintain 525 LL; if ct1 > -20 msec OR > -7, lower dosing to 350 mg LL
(What I mean by "less than <", I mean that the dosing was sufficient enough as to remove enough fibrotic scar tissue or steatosis that the measurement was more negative than -20 or -7). (The opposite holds for "greater than >"
. Step 6: Continue either same dose of 525mg or new dose of 350mg LL for the 2nd month.
Step 7: At end of 2nd month, again, repeat cT1 and PDFF and again calculate the change from previous month. Again, go back to Step 5.
Step 8. Repeat for 4 months or 16 weeks.
The idea is try to maximize the amount of scar tissue lost, change in cT1 or amount of PDFF lost, steatosis, by quantifying it monthly and reducing the LL dosage until the best results are elicited.
There will likely be other biomarkers which may be used, other than cT1 / PDFF, possibly Receptor Occupancy which could be measured on each physician visit to optimize treatment.
A phase 3 trial like this could be easily constructed.
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