HEPARC-2001 Extension

[qbeing1010]

brian_hammer2 started a thread on the YMB about this.   My question is:  how many people will be continuing the treatment? 58? What about the ones who received a placebo?

[Think2Succeed]

That's a mystery to me as well qbeing1010. I'm not aware of any management mention of a number of patients for this extension study. Also another mystery for me regarding this trial is that the original Heparc-2001 only enrolled E- patients and the extension study is supposed to enroll only patients from the original heparc-2001, however if you listened to the latest CC, management has stated that the extension study will have both E- and E+ patients enrolled ! Can anyone clarify this ?

T2S

[mudbug021]

Dr Given stated in the CC:

We are now focused on our global multiple-dose and combination Phase 2b
studies, which are currently enrolling patients. These studies are as follows:
(1) The 2002 study is testing ARC-520 + NUCS in NUC-experienced enegative
patients;
(2) 2003 is testing ARC-520 + NUCS in NUC-experienced e-positive patients;
(3) 2004 is our US-only study testing NUCS + ARC-520 in NUC-experienced
e-positive patients;

(4) A 2001-extension study is open to patients that were treated in our single
dose 2001 study. We will be testing ARC-520 + NUCS in e-negative and epositive
patients who are both NUC-experienced and NUC-naïve. Unlike
2002/3/and 4, this is open label so we have flexibility as to when we
disclose data.


(5) The final study in the series is 2008, or our MONARCH study. Let me say
a few words about this study which, as with the others, is currently enrolling
patients.

[Think2Succeed]

(4) A 2001-extension study is open to patients that were treated in our single
dose 2001 study.

Mud, go here: clinicaltrials.gov/ct2/show/NCT02065336?term=Arrowhead+Research+Corporation&spons=Arrowhead+Research+Corporation&rank=1

and look at the patient's key inclusion criteria :

Have a diagnosis of HBeAg negative !
Patients with > 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study.

So how come now they state E+ and Nuc Naive ? That doesn't make sense UNLESS they enroll new patients because the original heparc 2001 patients are ALL E- and NUC experienced patients !

T2S

[mudbug021]

@think2succeed  The only thing I can say is to keep in mind the "Estimated Enrollment" is just that, nothing is set in stone, so it is quite possible they can add more as time goes on. 

For qbeing1010 original question. Because of the way Dr Given stated; " extension study is open to patients that were treated in our single dose 2001 study." I have to assume all 58 prior to the extension would be eligible if they so desired. 

[Think2Succeed]

mudbug021 That's actually the only way the extension study can have E+ and Nuc naive patients...by adding new patients that were NOT part of the original Heparc-2001. It is still worth asking management for further clarification because as of now what is made public is confusing regarding this extension study.

T2S

[qbeing1010]

Did we ever learn any more on this topic?

Also, any theories on when the first dose of the extension may have occurred? Holdencf on YMB thinks we may be approaching the third dose now, but I'm not sure how he arrived at that.

[dig]

The heparc 2001 extention is open to all the paitents who participated in the original study. We know that was a total of 58 people. The company has said it is open to 55 people in the last CC. Why are 3 people no longer eligible? Just peaked my curiosity. In December they announced the the extension study. The way they worded the announcement tells me they had not started dosing it at that time. On 1 19 2016 the original study was updated to include the extension cohorts.

I have thought that China would approve ARC-520 well before the US. Allowing the extension to be multi-dosed at 4mg only strengthens this theory.

It is my guess they started the NUC nieve paitents on NUCS in December. If I recall this correctly thew wanted everyone on at least 30 days of NUC treatment.

It is my opinion they had everything in place waiting for approval. We know for sure they had approval on January 19 so conservatively they would have had the fist paitents dosed by February 1st.

[holdencf]

T2S & qbeing

There were originally 58 patients in 2001 which started as cohorts 1-4. all of which were eAg (-). Cohorts 5,6,7 were added all of whom were eAg (+).  Of the 58 patients, all will be offered the ability to participate including patients who received placebo.  (Although I think one of the patients either dropped out or never was dosed so the number might be 57)

files.shareholder.com/downloads/AMDA-2OTJP1/1569229211x0x851743/30D7A245-3259-41FB-8B46-6441C6E9346A/Sept_2015_AD_Presentation_Final.pdf

See page 9 on the above link if you want to confirm for yourself.

This is going to be a VERY telling study.  I think it will confirm the answers to questions surrounding eAg(-) late responders.  The eAg(+) will probably KD to undetectable HBsAg after 4 or 5 doses. Would love to see the eAg(-) achieve same at perhaps several doses later.  

And then Monarch also fascinating...see what happens in eAg(+) WITH and WITHOUT peg IFN.  

[holdencf]

Quick response to post about my YMB post concerning start of 2001ext/Monarch.

ARWR announced first Monarch patient dosing via PR 1/7/16.  I assumed they didn't make the announcement until a few days after the dosing.  So I just used 1/1/16 as a somewhat logical date.  Could have been a couple weeks before or a couple days later.  The study was "registered" by the CRO on clin trials on (I think) Oct 15, 2015.  They have a 60 day waiting period following initial screening/enrollment.  Assuming they started screening on or around the day they registered the study that would mean first patient would be dosable on 12/15/15. Since we can't come up with a "fixed" date, I just went with a slightly conservative 1/1/16.  If someone has a better methodology (such as grilling V. Anzalone) please post.

On the 2001 extension study, it is even more nebulous.  I spoke to V.A. in early January.  The best I could get out of him is that the effort to reach out to the original 2001 patients was under way.  I asked if they had dosed any of them.  "We aren't commenting on that."  


Answer to another post on NUC naive.  see page 9 of the AD presentation.  Cohort 7 (not in the initial study) was NUC naive.  clinicaltrials.gov can be a little deceptive.  Even though the CRO has the ability to change things, they don't always do that.  So the study can be a mix of the initial study language (all on NUCs) and new language that may or may not cover the addition of NUC naive cohort 7.

AD presentation
files.shareholder.com/downloads/AMDA-2OTJP1/1569229211x0x851743/30D7A245-3259-41FB-8B46-6441C6E9346A/Sept_2015_AD_Presentation_Final.pdf