Current ongoing Clinical Trials (updated 6/26/16)

[StayingUpbeat]

I'll do my best to keep this updated but anyone who sees new clinical trials for HSV therapeutics please back me up.

It's been a while since I've updated this since quite frankly not much is going on at the moment when it comes to open clinical trials for HSV therapies.  As of June 2016 there are only 2 confirmed clinical trials for HSV vaccines/therazines/treatments.  Anyone who is near a trial site and suffering from HSV should consider enrolling since it is the best way, short of becoming a medical researcher, to encourage progress.

HSV-2 Specific

1. (May 2016, Maybe) There is a rumor that the much anticipated Halford live attenuated vaccine is underway somewhere outside the US but details are sparse and anything out there is equally likely to be true or false.  His "Rational Vaccines" company just put up a splash page so that seems like an encouraging sign: http://rationalvaccines.com/
2. (Started in January 2016) a Phase I trial of a genital film used to prevent transmission of HSV (and HIV).  It would appear that the idea is for this to be used by people who don't actually have GHSV to protect the uninfected partner.: https://clinicaltrials.gov/ct2/show/NCT02579083?term=herpes+simplex&recr=Open&rank=8
3. (Started December 2015) a Phase I trials of a single subcutaneous injection of a monoclonal antibody called UB-621 in Taipei, Taiwan.  As the trial record hasn't been updated since 2015 and the total sought enrollment is 12 people this one has either been filled or cancelled.  The record still technically says "recruiting" so if you're living in Taiwan it might be worth an e-mail to the study coordinator to see what's up.  https://clinicaltrials.gov/ct2/show/NCT02346760?term=herpes&recr=Open&rank=39

HSV-1 Specific 

  Nothing relevant currently active
 

Pre-clinical

Sanofi + Immune Design: http://www.sanofipasteur.com/en/articles/sanofi-pasteur-and-immune-design-collaborate-on-a-vaccine-to-treat-herpes-simplex-virus.aspx

Once a year Dr. Brian Cullen posts an update on his progress regarding an HSV cure. It's decades away but also probably the only realistic shot we have at a sterilizing cure: http://cullenlab.duhs.duke.edu/faq/

Dr. Halford's has a blog in which he comments often on progress with his vaccine and (his opinion) on the state of HSV vaccine research. In particular for the current crop of vaccines: http://www.liveherpesvaccine.com

• Overall for gD Vaccines (GEN-003 specifically in the comments): http://herpesvaccine.scienceblog.com/2013/09/15/de-risking-hsv-2-vaccine-development/Agenus
• HerpV: http://herpesvaccine.scienceblog.com/2013/11/12/on-the-agenus-herpv-vaccine-trials/
• ACAM-529 (now HSV-529): http://herpesvaccine.scienceblog.com/2013/11/13/on-the-upcoming-acam-529-vaccine-trial/

Trials that are still going on but not recruiting

2. (Started in August 2015) a Phase I trial of the very important HSV-529 vaccine at UW.  This is a live attenuated virus vaccine developed by Dr. David Knipe of Harvard and brought to market by Sanofi Pasteur.  It is by far the most fundamentally legitimate vaccine of the bunch though very little is known about it's effectiveness as a therapeutic: https://clinicaltrials.gov/ct2/show/NCT02571166?term=HSV&rank=1

3. (2nd Phase II Trial wrapping up, Phase I/IIa Has Good Results) It should not be understated the importance of this vaccine having been the first one EVER to show a statistically significant reduction in shedding. The Genocea GEN-003 vaccine completed a Phase IIb clinical trial at A LOT of US sites. The results have been encouraging (though not long lasting). They are in the middle of another trial with sites all over the US: https://clinicaltrials.gov/ct2/show/NCT02515175?term=GEN-003&rank=3

4. (Partially completed some results released early 2016, the rest due out this fall) Admedus is running a trial of a DNA Plasmid vaccine developed by Dr. Ian Frazer (of HPV vaccine fame) in Brisbane Australia. In the phase I trial 95% of participants showed an HSV-2 T-Cell response (though the correlation of this number to reduction in symptoms is not known).  More recently there was a press release that claimed 90% reduction in lesions but for how long and what that means is somewhat unclear. http://www.admedus.com/au/admedus-vaccines-clinical-trial/

5. (Fully Enrolled, results anticipated early 2017) HSV-529 (formerly ACAM-529): Developed by Dr. David Knipe of Harvard, being manufactured by Sanofi Pasteur, and in a Phase I Clinical Trial at the National Institutes of Health in Bethesda, MD: http://www.niaid.nih.gov/volunteer/hsv529/Pages/default.aspx

Completed Trials

1. (update 12/15/14: completed, has results) Sublingual Ethel-Mercury (Thimerosal) on recurrent labial herpes. Beech Tree labs completed a phase 2 trial of using essentially an old topical anti-microbial on recurrent cold sores. They show pretty good success with this in a phase one and phase two trial and in veterinary applications: http://www.beechtreelabs.com/news It's unclear what their plans are with this "drug" but outside the US Thimerosal isn't actually that hard to come by.

2. (Updated 8/6/15: Completed, Has Results) A test of the effectiveness of Tenofovir as a gel and a film on HSV shedding. The gel was effective at preventing acquisition of HSV-2 but did little to impact shedding.

https://clinicaltrials.gov/ct2/show/NCT01989663?term=HSV&recr=Open&rank=60

3. (Update 6/29/15: Completed, has results) The Vical (nameless) Vaxfectin Formulated Vaccine in a Phase I/IIa clinical trial. Vaccine was unable to show a statistically significant reduction in shedding: http://www.wsj.com/articles/vicals-herpes-vaccine-didnt-meet-primary-endpoint-1435007017

4. (Completed appears to have run out of money) A trial of Squaric Acid Dibutyl Ester on recurrent labial herpes. This is a weird one but if it works it should also work on HSV-2. Its hard to explain briefly but I did a write-up about it here.

https://clinicaltrials.gov/ct2/show/NCT01971385?term=HSV&recr=Open&rank=86

5. (Completed, no results yet) open label trials of ASP2151 (amenamevir) in the UK given with various HIV drugs to test safety. These trials kind of suck. You get essentially two doses of ASP2151 and you take an HIV drug with the second dose to measure whether or not the two drugs together make you sick. It's unclear whether having HSV excludes you from the trial (if you don't say you have it they don't specifically ask) but if a couple days of relief is worth the headache of a half dozen blood draws maybe give it a shot. It probably pays pretty well.

https://clinicaltrials.gov/ct2/show/NCT02223351?term=asp2151&rank=1

https://clinicaltrials.gov/ct2/show/NCT02280421?term=asp2151&rank=4

https://clinicaltrials.gov/ct2/show/NCT02321748?term=asp2151&rank=6

https://clinicaltrials.gov/ct2/show/NCT02369172?term=asp2151&rank=7

https://clinicaltrials.gov/ct2/show/NCT02403635?term=asp2151&rank=8

https://clinicaltrials.gov/ct2/show/NCT02223351?term=HSV&recr=Open&rank=52

6. (Completed, no results posted) The company appears to have gone bust.  This was a trial of a snake venom based topical treatment called ZEP-3 in Natanya, ISRAEL. Appears to have had a decent phase I trial though efficacy is questionable.  They went under before the Phase II trial results could be delivered  (or they're really sitting on good results for a long time).  The only information about it is here.  The clinical trial listing is still up for anyone interested: https://clinicaltrials.gov/ct2/show/NCT02483182?term=Herpes&recr=Open&rank=13

Edited June 26, 2016 by StayingUpbeat

[Happy22]

Thank you for posting this list. I was wondering if anyone knows since when Bill Halford has had his vaccine?

[Juggalo]

Fix the first link by removing the point at the end.

[StayingUpbeat]

Main message above updated 12/15/14 to indicate the fully enrolled trials and details of Genoca's placebo roll-over trial.

[StayingUpbeat]

In it's recent Piper Jaffray webcast Vical indicates they expect preliminary results of their phase 1/2 trial to be released around 6/2015.

http://www.vical.com/investors/events-presentations/Event-Details/2014/Vical-to-Present-at-the-Piper-Jaffray-2014-Healthcare-Conference/default.aspx

[throwawayday345]

Sanofi's HSV-529 vaccine should be moved out of "pre-clinical", as it's currently in a Phase I trial: https://clinicaltrials.gov/ct2/show/NCT01915212?term=herpes&rank=5

[StayingUpbeat]

Sanofi's HSV-529 vaccine should be moved out of "pre-clinical", as it's currently in a Phase I trial: https://clinicaltrials.gov/ct2/show/NCT01915212?term=herpes&rank=5

There are two different HSV-529 vaccines in development. The "pre-clinical" one is the collaboration between Sanofi and a biotech named Immune Design that has not yet entered clinical trials. This is an attempt to improve the performance of HSV-529 with an adjuvant and it's still in pre-clinical development: http://www.immunedesign.com/pipeline/

The ongoing HSV-529 trial being sponsored by the NIH is essentially "raw" HSV-529 (i.e. no adjuvant) and is item #1 in the list of ongoing trials: http://www.niaid.nih.gov/volunteer/hsv529/Pages/default.aspx

You are absolutely correct that they are both HSV-529 related but HSV-529 + adjuvant trials haven't, to my knowledge, been announced yet.

---

[throwawayday345]

my bad you're right

[StayingUpbeat]

Updated with Admedus recently started phase II vaccine trial details.

[blue84]

Vical Reports Top-Line Results From Phase 1/2 Trial of Therapeutic Genital Herpes Vaccine

06/22/2015

The Primary Endpoint of Shedding Rate was not Met Conference Call and Webcast to be Held Today, June 22 at 5:00 pm ET

SAN DIEGO, June 22, 2015 (GLOBE NEWSWIRE) -- Vical Incorporated (Nasdaq:VICL) today announced top-line results from an ongoing randomized, double-blind, placebo controlled Phase 1/2 clinical study of its therapeutic genital herpes vaccine, designed to reduce viral shedding and genital herpes lesions in herpes simplex virus type 2 (HSV-2) infected patients. The trial enrolled patients across seven U.S. sites and is evaluating two constructs: a monovalent (gD) vaccine and a bivalent (gD + UL46) vaccine, each formulated with Vical'sproprietary Vaxfectin® adjuvant. The top-line analysis compared pre-vaccination measurements for each arm with those taken during the swabbing period in months 2 and 3 following the last vaccine dose. Neither the monovalent nor bivalent vaccine met the primary endpoint. On prospectively defined secondary endpoints, the bivalent vaccine achieved statistically significant reductions in the rate of genital lesions (-51%, p = 0.0037) and viral load from positive swabs (-0.39 log10, p = 0.0008) versus baseline. The results are summarized in the table below:

Monovalent

(N=54) Bivalent

(N=56) Placebo

(N=21)

Primary Endpoint

Change in shedding rate -12% -19% -45%

from baseline (p = 0.3862) (p = 0.1561) (p = 0.0144)

Secondary Endpoints

Change in lesion rate +3% -51% -46%

from baseline (p = 0.8759) (p = 0.0037) (p = 0.0850)

Change in viral load in -0.38 -0.39 0.28

positive swabs from baseline (HSV copies, log10) (p = 0.0012) (p = 0.0008) (p = 0.1268)

Both the monovalent and bivalent vaccines were generally well tolerated. Safety data have been reviewed throughout the trial by an independent safety monitoring board, and no grade 4 adverse events or serious adverse events related to vaccination have been observed.

"We just received the top-line study data and we are disappointed that the vaccines did not meet the primary endpoint," said Vijay Samant, President and Chief Executive Officer. "The trial is ongoing and all patients are being followed for safety for 12 months and efficacy for 9 months after their final vaccine dose. During that 9-month period, we will collect additional clinical efficacy data including recurrence rate and lesion rate, which will enable us to determine the appropriate next steps for this program. We greatly appreciate the ongoing support of the patients and investigators who are taking part in this trial."

Mr. Samant continued, "In the meantime, we remain focused on advancing our CMV vaccine candidate partnered with Astellas. Enrollment is complete in the Phase 2 solid organ transplant trial, placing us on track for data during the second half of 2016, and the Phase 3 pivotal trial is underway in hematopoietic stem cell transplant recipients. We are also moving our in-licensed antifungal compound toward a Phase 1 trial initiation during the first half of 2016. Because Astellas funds the CMV program and given the other operational efficiencies we have put in place, we anticipate that our current cash position will fund us through these milestones and into 2017."

About the Phase 1/2 HSV-2 Clinical Trial

The Phase 1/2 trial is an ongoing randomized double-blind, placebo controlled study which enrolled 165 symptomatic HSV-2 patients at seven investigational sites in the U.S. The trial consists of an initial dose escalation cohort with 14 patients and then an efficacy cohort with 151 patients at full dose. 131 evaluable patients are included in the top-line per protocol efficacy analysis.

Enrolled patients are required to have a history of symptomatic genital herpes with 2 to 9 lesion recurrences per year. The dose escalation component of the trial assessed the safety of ¼ dose, ½ dose, and a full dose of vaccines in a small number of patients prior to dosing additional patients at the full dose. Two vaccine constructs are being evaluated: monovalent (gD) and bivalent (gD + UL46), each formulated with Vical's proprietary Vaxfectin® adjuvant. Regardless of the vaccine construct and dose, all patients received a vaccine or a placebo on days 0, 28, and 56. The patients in the efficacy cohort who received the full dose of vaccine or placebo are assessed for vaccine effectiveness in reducing HSV-2 shedding from baseline as the primary endpoint, and for secondary endpoints including changes in lesion rate and viral load from baseline.

Each patient in the efficacy cohort performed once daily swabbing to measure HSV shedding before and after vaccination. Sampling periods of 60 days for daily swab collections and diaries were used to generate shedding and lesion data to compare the post-vaccination to the pre-vaccination periods. In addition, the quantity of virus during each positive shedding day was compared for each patient pre- and post-vaccination. All patients in the trial continue to be followed for safety for 12 months and efficacy for 9 months after their final vaccine dose, and during that 9-month period, additional clinical efficacy data including recurrence rate and lesion rate will be evaluated. Additional study details are available athttps://www.clinicaltrials.gov/ct2/show/NCT02030301.

Conference Call

Vical will conduct a conference call and webcast today, June 22, at 5:00 pm Eastern Time, to discuss the results of the trial. Listeners may access the accompanying slide presentation through the webcast at www.vical.com. The call and webcast are open on a listen-only basis to any interested parties. To listen to the conference call, dial in approximately ten minutes before the scheduled call to (719) 325-2430 (preferred), or (888) 523-1232 (toll-free), and reference confirmation code 6526980. A replay of the call will be available for 48 hours beginning about two hours after the call. To listen to the replay, dial (719) 457-0820 (preferred) or (888) 203-1112 (toll-free) and enter replay passcode 6526980. The call also will be available live and archived through the events page atwww.vical.com. For further information, contact Vical'sInvestor Relations department by phone at (858) 646-1127 or by e-mail at ir@vical.com.

About Vical

Vical develops biopharmaceutical products for the prevention and treatment of chronic or life-threatening infectious diseases, based on its patented DNA delivery technologies and other therapeutic approaches. Additional information on Vicalis available at www.vical.com.

Forward-Looking Statements

This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include Vical's projected cash runway, clinical plans and anticipated timelines, and expected announcement of data for clinical trials. Risks and uncertainties include whether Vical or others will continue development of Vical's HSV-2 vaccine or its other independent or partnered programs; unexpected expenses or cash requirements; whether any product candidates will be shown to be safe and efficacious in clinical trials; the timing of clinical trials; whether Vical or its collaborative partners will seek or gain approval to market any product candidates; and additional risks set forth in the Company's filings with theSecurities and Exchange Commission. These forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements.

CONTACT: Andrew Hopkins

[Type1aus]

It appears most vaccine are developed for hsv2 not hsv1... Is that because hsv1 suffers less?

[Zlice]

I wonder why Einstein and Halford didn't join together as they are both working with live.

how about aurx? Any info from them?

[Juggalo]

12 hours ago, Zlice said:

I wonder why Einstein and Halford didn't join together as they are both working with live.

how about aurx? Any info from them?

Aurx is a dead Project and has been dead for years. The only live trials on live vaccines is the HSV-529..

As potential pre-clinical Trials are those which include Halfords and Einstein/Yeshiva vaccine, but there is still not even Phase 1 in sight on these both..

Edited December 24, 2015 by Juggalo

[Zlice]

16 minutes ago, Juggalo said:

Aurx is a dead Project and has been dead for years. The only live Trials on live vaccines is HSV-529..

as well as potential pre-clinical Trials which include on Halfords and Einstein/Yeshiwa vaccine, but still not even Phase 1 in sight on These both..

well I mean if they work together they can speed things up right..

Aurx has been successful and it was in the phase III.

[Juggalo]

On ‎24‎.‎12‎.‎2015 at 1:18 AM, Zlice said:

well I mean if they work together they can speed things up right..

Aurx has been successful and it was in the phase III.

Not really, everyone wants to push their own product. people hold their own special patents and want to profit on their own work.

Edited December 26, 2015 by Juggalo

[EM424]

Anyone in Seattle?  UW and Fred Hutchinson are looking for participates for HSV529 Vaccine in HSV-2 Seropositive Adult

University of Washington Virology Research Clinic	Recruiting
Seattle, Washington, United States, 98104
Contact    206-520-4340    vrc@u.washington.edu    Link https://clinicaltrials.gov/ct2/show/NCT02571166?term=herpes+2&recr=Open&rank=4

[EM424]

Clinical trials can be found here:  ClinicalTrials.gov - Official Site

Mostly US but other countries often included.

[StayingUpbeat]

Updated with some recent information.  There is literally not much going on these days in the therapeutic clinical trial arena.  To put a positive spin on that maybe it means that there is a therapy being tested that everyone thinks will be a cure and therefore companies don't want to invest money in their own trials.  More likely is that there is simply a lull right now. 

@Vitaliy, To answer your question the only thing (relative to HSV) that has ever made it past a phase three trial is Acyclovir, Valacyclovir, and Famvir. 

[Evaluate]

On 2016-06-25 at 9:52 PM, StayingUpbeat said:

@VitaliyUpdated with some recent information.  There is literally not much going on these days in the therapeutic clinical trial arena.  To put a positive spin on that maybe it means that there is a therapy being tested that everyone thinks will be a cure and therefore companies don't want to invest money in their own trials.  More likely is that there is simply a lull right now.

I certainly feel the lull.  Months ago it felt like every week there was something new going on with research and now it seems like everything is standing still.  What I hope that means is lots is still happening in the background (e.g. Cullen/Bloom).

With so many vaccines underway at this time, some supported by okay pre or post-clinical data, it would be a bad financial idea to start up another vaccine.  While CRISPR is cooking away I still feel like other cure avenues are not being pursued.  My main hope right now, other than CRISPR, is that a study will happen upon information (perhaps not the main focus of the study) which will lead down a promising avenue.

[@lw@ys]

On ‎6‎/‎27‎/‎2016 at 11:23 PM, Evaluate said:

I certainly feel the lull.  Months ago it felt like every week there was something new going on with research and now it seems like everything is standing still.  What I hope that means is lots is still happening in the background (e.g. Cullen/Bloom).

With so many vaccines underway at this time, some supported by okay pre or post-clinical data, it would be a bad financial idea to start up another vaccine.  While CRISPR is cooking away I still feel like other cure avenues are not being pursued.  My main hope right now, other than CRISPR, is that a study will happen upon information (perhaps not the main focus of the study) which will lead down a promising avenue.

Call me crazy but doesn't it seem that this lull started right around the same time of the Einstein announcement?

[Maybe1day]

On 8/29/2016 at 8:50 PM, @lw@ys said:

Call me crazy but doesn't it seem that this lull started right around the same time of the Einstein announcement?

Which announcement? 

[@lw@ys]

23 hours ago, Maybe1day said:

Which announcement? 

Really?  Maybe I read too much

http://blogs.einstein.yu.edu/developing-a-herpes-vaccine-a-new-approach/

[Unsure88]

1 hour ago, @lw@ys said:

Really?  Maybe I read too much

http://blogs.einstein.yu.edu/developing-a-herpes-vaccine-a-new-approach/

This link goes nowhere....

[@lw@ys]

My apologies. Try typing "Betsy Herold Einstein HSV" into Google I am sure you will find several pages with info.

Edited September 1, 2016 by @lw@ys

[Maybe1day]

On 8/31/2016 at 11:16 PM, @lw@ys said:

My apologies. Try typing "Betsy Herold Einstein HSV" into Google I am sure you will find several pages with info.

Last I read from Einstein was their approach was to find a preventative vaccine... not therapeutic