London South East prides itself on its community spirit, and in order to keep the chat section problem free, we ask all members to follow these simple rules. In these rules, we refer to ourselves as "we", "us", "our". The user of the website is referred to as "you" and "your".
By posting on our share chat boards you are agreeing to the following:
You will only have one login account. Registering with multiple accounts is not allowed. Any user found to have more than one account on this site will have all, and any future accounts suspended permanently.
Your email and password must only be used by you. If a post is made under your account, it will be considered that it was posted by yourself.
Your account nickname must not be the same, or contain, listed company names or board members' names.
While debating and discussion is fine, we will not tolerate; rudeness, swearing, insulting posts, personal attacks, or posts which are invasive of another's privacy.
You will not;
discuss illegal or criminal activities.
post any confidential or price sensitive information or that is not public knowledge.
post misleading or false statements regarding the share price and performance. Such posts are deemed as market abuse, and may be reported to the appropriate authorities.
post any private communication, or part thereof, from any other person, including from a member of the board of directors of a listed company. Such posts cannot be verified as true and could be deemed to be misleading.
post any personal details (e.g. email address or phone number).
post live price or level 2 updates.
publish content that is not your original work, or infringes the copyright or other rights of any third party.
post non-constructive, meaningless, one word (or short) non-sense posts.
post links to, or otherwise publish any content containing any form of advertising, promotion for goods and services, spam, or other unsolicited communication.
post any affiliate or referral links, or post anything asking for a referral.
post or otherwise publish any content unrelated to the board or the board's topic.
re-post premium share chat posts on regular share chat.
restrict or inhibit any other user from using the boards.
impersonate any person or entity, including any of our employees or representatives.
post or transmit any content that contains software viruses, files or code designed to interrupt, destroy or limit the functionality of this website or any computer software or equipment.
If you are going to post non-English, please also post an English translation of your post.
If you are going to post non-English, please also post an English translation of your post.
The IP address of all posts is recorded to aid in enforcing these conditions. As a user you agree to any information you have entered being stored in a database. You agree that we have the right to remove, edit, move or close any topic or board at any time should we see fit. You agree that we have the right to remove any post without notice. You agree that we have the right to suspend your account without notice.
Please note some users may not behave properly and may post content that is misleading, untrue or offensive.
It is not possible for us to fully monitor all content all of the time but where we have actually received notice of any content that is potentially misleading, untrue, offensive, unlawful, infringes third party rights or is potentially in breach of these terms and conditions, then we will review such content, decide whether to remove it from this website and act accordingly.
Premium and Verified Members
Premium Members are members that have a premium subscription with London South East and have access to Premium Chat. You can subscribe here.
London South East does not endorse such members, and posts should not be construed as advice and represent the opinions of the authors, not those of London South East Ltd, or its affiliates.
The inclusion and exclusion criteria and the groups are described in the master protocol. Not exactly the same for everyone there is also differentiation in how many days since positive test and others. Apart from other factors placebo are shared between 2 or more only if the inclusion criteria are the same.
Doc on your question re P3 they do have the chance of changing the protocol just for SNG or for all non I/V since it hasn't been published yet. However it was the intention that the P2 patients would form part of the extended trial and therefore they would not readily change the patient selection parameters without very good reason.
I suppose accessibility issues would also cover the fact that not all drugs in the trial will be available at all locations. Overall it would probably not be possible to make the whole trial 'drug random' within the total trial patient population for various reasons.
Doc, I think you are right though that Synairgen have little or no control over either patient selection or protocol. As you say this was a decision the BoD made to relinquish control which perhaps contrasts with the decision made re UK Recovery trial. The difference is the Activ-2 inclusion came after the international P3 had been organised.
I am interested that the Acitv-2 is now going international. This may not affect us for P2 but if we are rolled into P3 more drug will be needed for availabilty in multiple locations.
Ghia Given the limited number of trial drugs in Activ-2, although the intention was to share the control group where possible I am not clear whether there will be the same number taking dummy inhaler as real SNG or dummy tablets /Camostat or whether the Control (placebo) group will be the aggregate of all those on placebos be it dummy I/V or inhaler. In the latter case if there were four drugs and four methods of administration they could have 100 people taking each real drug and 25 people each taking the complementary placebo split say 25 I/V, 25 I/M, 25 tablets and 25 inhaler. If this was done it would mean that 4 x as many people in each group would be on the real thing. I don't know therefore if the NIH would not release this information in case it could be bias inducing. I think people can understand a 50:50 chance but with only 1 in 5 or 20% chance of having a placebo this could enhance the placebo effect.
After having written that I suppose the same argument could have been made if all the treatments were say tablets and only 20% were placebo so this has obviously been taken on board in terms of the protocol and discounted so perhaps indeed there will be only 20% on placebo in each trial type. Lazily, I haven't re-read the protocol to check this is the case but I recall it does say something about matching placebo type to real drug and some number crunching being necessary.
Doc - just read the clinical trials register for Activ2 again and whilst the Placebo arm maybe shared across drugs which involve the same delivery method it looks like SNG will not share a placebo Arm since it is the only inhaled drug.
“ Placebo Comparator: Placebo (Inhaled solution) The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way. If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study”
My guess is they have primed different sites with different drugs, so SNG will be trialed out of a subset of sites and randomised drug placebo accordingly at those sites.
Spin For my part I have to confess I'd assumed from the start that the sharing of placebo patients was a clever functonal device - to make them go further - but hadn't realised the assigning of treatments was also random. Seems bizarre to say the least - with different drugs working in different ways and for different populations. I guess in order to be accepted onto Activ-2 Syn had to dispense with the age and health targeting it had used in both arms of SG016 and for the International P3. It's must be something of a gamble for Synairgen to relinquish the controls already established and proven. Presumably it's the same trial design for Activ 3 ?
Spinnaker - I think the risk profile came from one of the Kansas University broadcasts. From memory the comment was something like some treatments will be unavailable to all patients due to accessibility issues.
Some trial applicants may have accessibility issues that mean they cannot for instance use an inhaler due to a disability or they may not be able to attend the drop in centre to receive an IV infusion etc.
That is only from memory though I'll try and find the source.
Interesting link Doc. I had asked a question to myself whether there would be any element of choice either by the patient and or the doctor in charge as to which trial drug group each patient would enter. I assumed, but without evidence that the doctor might have a say but the patient might not. Also some of the centres may only have some of the options available. This is certainly the case for our drug which we know has not been made available to all the participating centres.
This 21 April addition of SAB 185 comes with the statement that not only will the selection of treatment be random but also that Activ-2 is recruiting centres worldwide.
I am therefore confused.
Probatis could you please post a link to your statement re low risk and high risk separation please because that does not sit squarely to the 'random' statement in the 21 April notice from NIH.
Whilst posting I saw and noted that only one trial drug in Activ-2 has been granted EUA so far and that took 3 and a bit months. At the time it was the only drug in the programme. Extract from https://www.niaid.nih.gov/news-events/statement-four-potential-covid-19-therapeutics-enter-phase-23-testing-nih-activ-2-trial 'On August 4, 2020, NIAID announced the launch of ACTIV-2, which initially tested LY-CoV555, a monoclonal antibody made by Eli Lilly and Company. On November 10, 2020, LY-CoV555, also known as bamlanivimab, was granted Emergency Use Authorization by the U.S. Food and Drug Administration (FDA) for treating mild-to-moderate COVID-19 in adults and children over 12 years old who are at high risk for progressing to severe COVID-19 and/or hospitalization. An ACTIV-2 study testing BRII-196 and BRII-198, investigational neutralizing monoclonal antibodies manufactured by Brii Biosciences (Durham, N.C., and Beijing), was announced by NIAID on January 5, 2021, and is continuing to enroll volunteers.'
Also notable is the BRII drugs added on Jan 5th 2021 still have no read-out and were added a month or so before SNG on Feb 10th.
We have to keep patient and hope that the limited supply of SNG001/ limited number of locations where it is available will not adversely impact the overall take-up in the trial compared to the other drugs being trialed.
A Phase 2/3 trial to evaluate a new fully-human polyclonal antibody therapeutic targeted to SARS-CoV-2, called SAB-185
Most intersting is this paragraph which describes enrollment. I knew the placebo group was shared but not trial drug allocation
"When participants enroll in ACTIV-2, they will be assigned at random to receive either SAB-185, another therapeutic currently being evaluated in ACTIV-2, or a placebo. Other therapeutics currently being evaluated in ACTIV-2 include: a regimen of two experimental antibodies, BRII-196 and BRII-198, developed by Brii Biosciences based in Durham, North Carolina and Beijing; SNG001, an inhalable beta interferon developed by Synairgen based in Southampton, United Kingdom; AZD7442, a long-acting monoclonal antibody combination administered by either an intravenous infusion or an intramuscular injection, developed by AstraZeneca based in Cambridge, United Kingdom Camostat mesilate, an orally administered serine protease inhibitor developed by Sagent Pharmaceuticals based in Schaumburg, Illinois.