Any news on the Inform -1 trials

[bradlybone]

Any one have news on this trial for using a new combo of polymearase and protease inhibitors with out interferon and riba? It's been going on in Australia and New Zeland and is a join effort by Rosche, Intermune, and one other. 14 week trial, pills twice a day. No shots not interferon, no riba.

News is supposed to be releases April 25 At ELDS meeting.(might have the acronym wrong)

Anyone?

[GreatBird]

Fancy meeting you here. :)

This was posted earlier today. I think it's what you're talking about:

http://www.medhelp.org/posts/show/797886

[Fathom500]

Here is the text from the link I posted Friday. Some folk on another forum I visit are checking with some of the Austrailian HCV forums to see if they can get ahold of anyone who was actually in the trials. I've also read that this was tried in chimps with some good results.

FIRST-IN-MAN DEMONSTRATION OF POTENT ANTIVIRAL ACTIVITY WITH A NUCLEOSIDE POLYMERASE (R7128) AND PROTEASE (R7227/ITMN-191) INHIBITOR COMBINATION IN HCV: SAFETY, PHARMACOKINETICS, AND VIROLOGIC RESULTS FROM INFORM-1

Introduction: The combination of two potent direct-acting antivirals (DAAs), targeting two distinct viral enzymes, may offer advantages over single DAA strategies by enhancing potency, reducing the emergence of drug resistance, and possibly eliminating the need for PEG-IFN +/- ribavirin. The combination of R7128/R7227 offers the potential for a highly potent regimen with a high genetic barrier to resistance.


Methods: INFORM-1 is a randomized, double-blind, ascending dose Phase I trial. Treatment-naïve HCV-infected adults (genotype-1), received up to 14d oral combination therapy. Groups A and B received low dose monotherapy with R7128 (A, n=8) 500mg q12h or low dose R7227 (B, n=9) 100 mg q8h on d1-3, both followed by combination R7128/R7227 on d4-7. Groups C-F (8 active/2 placebo) receive 14d R7128 (mg q12h)/R7227 (mg q8h): 500/100, 1000/100, 500/200, and 1000/200. Safety, viral kinetics, resistance, and pharmacokinetics of R7128/R7227 are evaluated in all cohorts.

Results: Groups A-C (n=27) have been completed with no treatment-related SAEs, dose modifications, or discontinuations. Pharmacokinetic analysis confirmed no drug-drug interaction. The HCVRNA change from baseline for both Groups A and B at d7 was similar (combined mean (SD) -3.0 (0.8) Log10 IU/mL). In Group C after 14d low-dose combination, the mean (SD [range]) change from baseline was -3.9 (0.8 [-5.0 to -2.9]) Log10 IU/mL, with 1 patient undetectable (Figure 1). The combination of R7128 and R7227 provided greater than additive antiviral activity, with no viral rebound (sustained viral load increase > 0.5 Log10).

Conclusions: The orally administered combination of low dose R7128 and R7227 provided significant antiviral potency, suppressed viral rebound, and appears safe and well-tolerated for 14 days. Higher doses and twice-daily regimens are being evaluated in additional cohorts. These results confirm for the first time that a protease and nucleoside polymerase inhibitor can be combined in vivo, and remain a promising combination for future treatment.

[Fathom500]

I also found out last week that one of the companies involved (Pharmasset) uses the high end servers that I design at my day job to model the virus and the molocules used in the inhibitors. So there is a good chance I will get to do a customer visit at their site sometime in the next year or so.

This makes me feel that in some small way I can actually help the cause. Maybe that,s crazy but it makes me feel motivated to design the best servers I possible can. Not just for the company but for all of us.

[bradlybone]

I've been on a few Aussie sites, and have posted but the lid is on.  A few of the Aussies think the lab rats had to sign non disclosure agreements.

A few years back I declined a 191 (R2772 now)trial as it was for tolerability and not efficacy.

Now I've put out feelers for any non-responder/relasper trials using this combo but none are published to date although there have been rumors. I did that with VX 850 but started double dosing interferon instead. That may have been a mistake since a friend got on the VX-950 (teleprivar) trial who was a non responder and she's now SVR.

I am not.

Bradlybone