Clinical Trials of Monoclonal antibodies AZD7442 against SARS=CoV-2 (COVID19) - majority of sites in UK and USA

[Jm954]

There are two clinical trials of monoclonal antibodies that target covid19.

AstraZeneca is developing mAbs to the SARS-CoV-2 S protein. The SARS-CoV-2 spike protein contains the virus's RBD, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, is expected to block infection. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit and decrease Fc effector function in order to decrease the potential risk of antibody-dependent enhancement of disease.

Monoclonal antibodies are artificially produced in a laboratory and designed as possible medical treatments. They are designed to be injected directly into the body, unlike vaccines which ‘train’ the immune system itself to produce antibodies.

AZD7442 is a combination of 2 of these mAbs (AZD8895 and AZD1061) and is being evaluated for administration to prevent and/or treat COVID-19.

The first trial is called STORM CHASER - a Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults. This is two doses of antibody. STORM CHASER is exploring the use of a combination of monoclonal antibodies given intramuscularly in those who have been exposed to SARS-CoV-2 – a setting where vaccination would not have time to work and we have no other proven therapies to date. This makes STORM CHASER an important study that may have a large impact on our ability to control this infection.

The second is called PROVENT - a Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adults. This is a single dose of antibody and the trial is for people who may not respond to vaccination (for instance where someone has a compromised immune system) or are at increased risk of Covid-19 infection due to factors such as age and existing conditions. As licensed vaccines become available to qualifying trial participants, a mechanism will be put in place to enable them to safely leave the study if deemed medically beneficial. Being a trial participant in one of the studies will not delay the process of receiving a vaccination and should not prevent patients being involved in other studies if they do develop an illness related to Covid-19. Note that there is currently no provision to cross over if the MAB arm proves beneficial.

BOTH trials involve the use of placebo as the comparator arm with a 2:1 randomisation of AZD7442:saline placebo so you may not get the antibody. The trials are double blinded so not even your doctor or trial worker will know what you have received.

The vast majority of sites are in the USA but STORM CHASER has sites 6 UK sites with 1 London site (NW1 2BH) recruiting at the moment. Other UK sites include Southampton SO16 6YD; Wakefield WF1 5RH; Hull HU3 2KZ; and Manchester M8 5RB; and another London site EC1A 7BE.

PROVENT is also massively recruiting in USA but also France, Belgium, Spain as well as the 8 UK sites which include Enfield, EN1 1LJ; Hayle, TR27 5DT: London,WC1N 3BG; Preston, PR1 6YA; Rochdale, OL11 4AU; Southampton, SO16 6YD; Torpoint, PL11 2TB; Wakefield, WF1 4DG

More here: uclh.nhs.uk/news/uclh-doses...

STORMCHASER: clinicaltrials.gov/ct2/show...

PROVENT: clinicaltrials.gov/ct2/show...

Jackie

[UK-Sparky]

Thanks Jackie, I am hopefully going to a Provent Trial Centre on Thursday, will let folks know how it goesMarc

[Newdawn Administrator in reply to UK-Sparky]

Good luck with that Marc. As a matter of interest, do you know from your enquiries if the trial centres are distributed around the country or concentrated near the trial hospital in London, UCHL?

Newdawn

[UK-Sparky in reply to Newdawn]

Sadly seems to be London based, I am in Milton Keynes and trial centre is Enfield 40 miles away but think it is worth it!

[Newdawn Administrator in reply to UK-Sparky]

Thanks Marc. I suspected as much and as I’m at the opposite end of the country, travelling just now wouldn’t be possible.

Good luck with your application.

Newdawn

[Jm954 Administrator in reply to Newdawn]

I've listed them in the post Newdawn, not sure if any in your area.Jackie

[Newdawn Administrator in reply to Jm954]

Thanks Jackie, I missed that! I think I’m on Covid information overload just now and my brain is starting to scream! 😱 I suspect we are going into full lockdown once the PM has been on tonight which will make life more difficult. The idea of receiving the placebo doesn’t appeal either.

Newdawn

[bennevisplace in reply to UK-Sparky]

Hi Sparky, was telephone interview not an option then?

I did the initial screening and am waiting to hear from UH Southampton.

[UK-Sparky in reply to bennevisplace]

yes was pre screened but know BP, weight, fitness, any complications will be discussed at my appointment friday before if all goes well I get a jab in each buttock!

[bennevisplace in reply to UK-Sparky]

Thanks, hope it goes to plan.

[Ernest2]

Many thanks Jackie and a very Happy New Year. That sounds like potential real good news.

One bit I didn't understand was the bit about crossover. If the MAB arm looks beneficial assume those on the saline would want to cross over to the MAB (might be circumstance dependent), but as I read it that's what is not allowed?

Best wishes,

Ernest

[Jm954 Administrator in reply to Ernest2]

Yes, you're right.Often in trials like this, when the treatment arm shows a clear benefit, patients on the placebo arm are allowed to cross over and receive the treatment but that isn't allowed on this trial. That's not to say that they won't do a trial amendment and enable that in the future but it's something to be aware of at the moment.Jackie

[Justasheet1]

Jackie,

I just looked at both of them and unless I am mistaken, you’re excluded if you had the vaccine and also in my case if you had an infusion reaction to Gazvya or Rituxin.

Jeff

[Newdawn Administrator in reply to Justasheet1]

True Jeff. You have to leave the trial if you have the vaccine and it’s also not open to those on IVIG.

Newdawn

[Jm954 Administrator in reply to Justasheet1]

yes Jeff, I'm afraid so.

[wroxham-gb in reply to Justasheet1]

Hi JeffWhereabouts did you read that about reaction to Retuxinmab making you a no-no for the trial.

Sue

[Justasheet1 in reply to wroxham-gb]

Sue,

I clicked on both provided links to Clinictrials.gov and it was there under exclusions for both. Adverse reaction to mab’s

Jeff

[wroxham-gb in reply to Justasheet1]

Thanks Jeff, I missed that point somehow.Sue

Ps love to Theo.

[Justasheet1 in reply to wroxham-gb]

Sue,

#4

“Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.”

Jeff

[wroxham-gb in reply to Justasheet1]

Admit disappointed too Jeff. I've always had to be hospitalized for my Rixtuximab infusions( all 14). Due to reactions.Sue

😢

[Justasheet1 in reply to wroxham-gb]

Sue,

My first rituxin reaction was interesting and my first obinutuzamab was even worse but always well managed by the medical staff and only for the first infusion.

Theo says hi!

Jeff

[wroxham-gb in reply to Justasheet1]

I second that the medical staff are brilliant.Stay safe.

Sue

[Justasheet1]

☹️

[ChrisLovesLife]

Fascinating news Jackie, thank you, as always for fantastic information. I was just reading Chaya Venkat's article on CLLtopics.org regarding the use of Regeneron's IVIg monoclonal antibody preventative treatment in CLL patients. The technology is moving at lightning speed, offering much hope to us patients!

[fapumpkin]

Hello Jackie, I wonder if one of these is the trial I posted about a little while ago? If it is, then I think there maybe a Doctors surgery in Torpoint that was recruiting. I did ask the trial nurse at my local hospital about the trial but I was told that sadly, as I am already on a trial (Flair, rituximab/ibrutinib arm) that I can not join another trial. I think there are 9 sites for the trial in the uk?

cornwalllive.com/news/cornw...

“AstraZeneca has started a Phase III trial evaluating whether an experimental long-acting monoclonal antibody combination is effective at preventing COVID-19 in at-risk groups, such as the immunocompromised, for up to 12 months.”

[Jm954 Administrator in reply to fapumpkin]

Yes, Torpoint is one of the locations. 😊. Disappointing that you couldn’t take part.

[UK-Sparky in reply to fapumpkin]

That is interesting I said I am on Flair trial and check with Flair and AZ team, did not stop me being put forward.

[Etoile7]

Not sure they would really admit CLL patients...as those / we have been excluded in all the previous Covid trials?

[Jm954 Administrator in reply to Etoile7]

Hi there, hope you're well. This is from the UCL website: "PROVENT, is looking at use of AZD7442 in people who may not respond to vaccination (for instance where someone has a compromised immune system) or are at increased risk of Covid-19 infection due to factors such as age and existing conditions. UCLH infectious diseases consultant Dr Nicky Longley is leading the UCLH portion of PROVENT.


Dr Longley said: “We will be recruiting people who are older or in long-term care, and who have conditions such as cancer and HIV which may affect the ability of their immune system to respond to a vaccine. We want to reassure anyone for whom a vaccine may not work that we can offer an alternative which is just as protective.”

We have a few members who are looking to sign up.

Jackie

[Smakwater]

More great stuff from Jackie,

Covid might seem to some an endless hopeless antagonist, however, so was the flu, aids, the plague. Sharing this knowledge gives people hope against the endless antagonist.

I heard someone say once, "You are either part of the problem, or You are part of the solution". The more people become aware of the probability for a solution, the greater the solution dynamic.

Thank You,

JM

[Jm954 Administrator in reply to Smakwater]

So true