This if for the trial experts(you know who you are)

[EyesofBlue55]

Ok got a call from a study nurse here in Atlanta about a trial they will be starting up in 3 weeks.Its #NCT 00743975on Clinical trials in Atlanta.I was hoping some of you (Bill,Trinity,NYGirl,Specda))could look at it and tell me what you think.There will be three arms in this trial.

Havent had too many questions lately but read everyones posts all the time. I just dont know too much about the trial thing...thx  cindy

[orphanedhawk]

Some people go to their graves with hep C, not because of it, and never knew they had it.

Why in the world would you want to do this when you might never, ever have any problems from HepC??

Wait for something safer and surer to become available.

[RobertBeWell]

"GS-9190 is a non-nucleoside HCV NS5B polymerase inhibitor. From what I understand polymerase inhibitors do not have the same long term resistance issues that the Protease inhibitors do. Since they do not interact with the virus in the same manner that the protease inhibitors do (like boceprevir and telaprevir) they should not create a resistance problem that would prevent you from treating again with a protease inhibitor. "

That is absolutely correct. They attack the virus at completely different structural points. Exactly the reason they are hoping that one day, treatment without IFN/RIBA will be possible through the use of multiple DAA's.

Robert

[spectda]

I believe that is a wise decision Cindy. If you had advanced disease your options would be different and it might be a good idea. I believe that when the time comes you will be glad that your doctor's and your treatment decisions are not dictated by trial guidelines.

GS-9190 is a non-nucleoside HCV NS5B polymerase inhibitor. From what I understand polymerase inhibitors do not have the same long term resistance issues that the Protease inhibitors do. Since they do not interact with the virus in the same manner that the protease inhibitors do (like boceprevir and telaprevir) they should not create a resistance problem that would prevent you from treating again with a protease inhibitor.

Good Luck - Dave

[EyesofBlue55]

Thanks guys.I was hoping for a response like this from you all.It just sounded real good coming from the trial nurse......I will wait for new PI's.Im just ready to get rid of this thing!!!!!!!Grade 2  Stage 0 Viral load last draw 16,000,000.  Thx Cindy

[nygirl7]

Read Spectdas great post on clinical trials Cindy it will help you understand what we are trying to say.

"Most drugs that enter phase II studies do not progress on to phase III studies.  This is because the drug is being tested in more people for a generally longer period of time so lack of effectiveness and a better picture of the effectiveness emerges."

[nygirl7]

Cindy it's not all about great VL reduction by week 8 thats good but not the all important factor. If you have seen some of the other trials that have come and gone they start out with a bang then fizzle out and folks haven't gotten to SVR. Getting to UNDETECTIBLE and STAYING there is the only goal you really need to have. Forget great reduction by week 8 - there was one that got people to almost UND by the first SHOT but it did not get them to clear the virus.

Plus you don't know if this drug will have some effect that will prevent you from taking the PIs later. Or if it will create a mutant strain that will make it impossible for you to clear...things like that.

With zero liver damage you are in no rush. Wait for the PIs to come out - I totally agree.

[djbn13]

• Severe chronic obstructive pulmonary disease

Why I can't get in a trial and may not be able to do tx. The others are right, wait for the new drugs.

[spectda]

I completely agree with flguy, why participate in a trial if you have minimal damage and can wait for boceprrvor and teleprevir next year, especially with a relatively unknown drug and a chance of a placebo. You give up a lot of control and imput about your treatment when you participate in a trial. Be patient and wait.  

[Trish77]

More readable details for you on the Phase I study.

http://www.allbusiness.com/medicine-health/medical-science-pharmacology/5304444-1.html

You might want to follow up on this part:

http://www.natap.org/2007/AASLD/AASLD_17.htm

Your doctor should have results of the QT study Gilead is supposed to have done after the Phase I trial.  That might be why they're going with 40mg bid but also it seems to be the dosage which delivered the best results.

I don't know your stats, Cindy.  What stage of liver damage are you at?  This is a Phase II study with a drug that's been trialled for an 8 day period.  

[FlGuy]

Based on what you've previously written you'd be crazy to go for this. Geno 1, Stage 0 and good insurance, age 55. The drug has no significant track record, it's a Phase 2 trial and the duration is 48 weeks.

Teleprivir will be out relatively soon (you have no damage) with proven effectiveness against Geno 1 and SOC will likely be 24 weeks.

I don't think this decision requires a lot of thought.

[EyesofBlue55]

Correction to post 9 hrs ago.Viral load cut tremendously by DAY 8!!!

[EyesofBlue55]

Thanks I had already reiewed all the info before posting..What I really need is some feedback and opinions.Does this look like a pretty good one?

[HectorSF]

PART 2

Exclusion Criteria:
• Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
• Males who have partners planning to become pregnant
• Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week 72. One method should include a condom with spermicide for males
• Infection with non-genotype 1 HCV
• Poorly controlled diabetes mellitus (hemoglobin A1c > 7) unless treatment intervention has been reviewed with the Medical Monitor and improved glucose control is anticipated
• History of sarcoidosis
• History of hemoglobinopathy (e.g., thalassemia)
• History of known retinal disease
• History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen)
• Evidence of hepatocellular carcinoma
• Chronic liver disease of a non-HCV etiology
• Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
• Co-infection with HIV, HBV, or multiple HCV genotypes
• Chronic use of systemic immunosuppressive agents
• Presence of autoimmune disorders. Subjects with treated hypothyroidism with normal TSH may be enrolled.
• Severe chronic obstructive pulmonary disease
• History of clinically significant cardiac disease, including a family history of Long QT Syndrome, and/or evidence of the following ECG abnormalities at screening: QTcF (QT corrected using Fridericia's formula) of > 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of > 120 msec; bradycardia ( 40 msec or depth of > 0.4 to 0.5 V); arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ; ventricular pre excitation; second or third degree heart block
• Positive urine screen for amphetamines or cocaine
• Known, current heroin, morphine, or methadone use
• Ongoing alcohol abuse in the judgment of the investigator (in no case intake of more than 28 units of alcohol per week [1 unit = ½ pint of beer, 1 glass of wine, 1 shot of spirits])
• Receiving a known potent CYP 3A4 inhibitor within 2 weeks of study drug dosing or are expected to receive such therapy during the course of study drug dosing
• Known hypersensitivity to the study drugs, their metabolites or formulation excipients
• In the judgment of the Investigator, should not participate in the study due to potential clinical or compliance issues

Hectorsf

[HectorSF]

Here is the study...PART 1

http://clinicaltrials.gov/ct2/show/NCT00743795?intr=%22GS-9190%22&rank=2

NCT00743795

Safety, Tolerability, and Antiviral Activity of 24 or 48 Weeks of GS-9190 in Combination With Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection

This study is ongoing, but not recruiting participants.

First Received: August 27, 2008   Last Updated: September 24, 2010  

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
•Undetectable HCV RNA level [ Time Frame: At Week 12 for Early Virologic Response (EVR) ] [ Designated as safety issue: No ]


Secondary Outcome Measures:
•Safety and tolerability [ Time Frame: Throughout 72 week study period ] [ Designated as safety issue: Yes ]

•Undetectable HCV RNA level [ Time Frame: Week 4, Week 24 and Week 48 ] [ Designated as safety issue: No ]

•GS-9190 plasma concentrations [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]

•Undetectable HCV RNA [ Time Frame: At Week 72 for sustained virologic response (SVR) ] [ Designated as safety issue: No ]

Detailed Description:
The safety, tolerability and antiviral efficacy GS-9190, administered orally twice daily at 40 mg, will be compared to placebo when used in combination with peginterferon alfa 2a (PEG) and ribavirin (RIBA) in treatment-naïve subjects chronically infected with HCV genotype 1 infection. Two-hundred (200) subjects will be randomized (50/100/50) to one of three treatment arms:

Arm 1: PEG/RIBA + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)

Arm 2: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)

Arm 3: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).

Randomization will be stratified by plasma HCV RNA level (< or ≥ 400,000 IU/mL) at screening and race (of African descent or other).

In order to ensure adequate representation of subjects with genotypes 1a and 1b in this trial, enrollment for either genotype will be capped at 120 subjects. Once 120 subjects of either genotype (e.g., genotype 1a) have been randomized, subsequent enrollment will only be allowed for subjects with the other genotype (e.g., genotype 1b).

The duration of double-blind treatment is 48 weeks plus 24 weeks of treatment-free follow-up; however subjects in Arm 3 will stop all medication at Week 24 if they have achieved an RVR (defined by undetectable HCV RNA following 4 weeks on therapy) and have maintained that response thereafter. Subjects will only learn that they have been randomized to Arm 3 if, at Week 24, having achieved criteria for stopping therapy, they are instructed to stop. All other subjects will remain blinded to their treatment status throughout the course of the study.

The standard of care treatment stopping criterion used in clinical practice when treating HCV with PEG/RIBA, failure to achieve EVR, will be utilized in this trial. Additionally, subjects with detectable plasma HCV RNA at Week 24 will discontinue all study medications no later than the Week 28 visit and will be followed off-treatment for 24 weeks.

Enrollment: 252
Study Start Date: October 2008
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility
Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
Inclusion Criteria:
• Adult subjects (18 - 70 years of age)
• Chronic HCV infection for at least 6 months prior to Baseline (Day 1) (anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator)
• Liver biopsy results within the past 2 years prior to Baseline (Day 1) indicating the absence of cirrhosis
• HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
• Mono-infection with HCV genotype 1a or 1b
• Detectable plasma HCV RNA at Screening
• BMI between 19 and 36 kg/m2
• Willing and able to provide written informed consent and to comply with all study requirements
• Of generally good health as determined by the Investigator
• Subject agrees to use adequate skin protection (e.g., sunblocking agent) when exposed to the sun.
• Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal  40 mIU/mL. If the FSH is ≤ 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study.
• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA

Cheers!
Hectorsf

[EyesofBlue55]

Its a 3 arm blinded study.I guess if they tell you to quit ay week 24 that you got into  arm  3????

[EyesofBlue55]

Its trial #39 on Clinical trials .Its using a new drug called GS9190.I understand some of it but some I dont.I guess if you get into the third arm of the trial and get to RVR by week4 you only will do tx for 24 weeks.I googled the drug and viral load drop was tremendous by week 8!!!The trial nurse said that it was gonna be a good one to get into but I want some opinions first.THX cindy

[spectda]

I tried to look up that number NCT00743975 on the clinicaltrials.gov site and it didn't come up/ What drugs are they using, perhaps it can be searched that way. Or if you have the link that would be better.

- Dave