Member Info for Peelweight

PMJH, a huge welcome back! Delighted to see you posting. Agreed, a waiting game but as you say much to wait for ...

GLA

Yenom,

Yes that's true, the DMC can call futility or a definite positive effect prior to the end of the official randomisation.

Richlist, agreed, a full application for license would be sought if results mirror P2. Because that is not instantaneous, an EUA would be applied for in the interim at the same time. That can be granted immediately, pending the full decision on licensing in each jurisdiction IMHO

Sites announced

US x3
Belgium x3
France x2
India x5
Israel x2
Portugal x3
Serbia x4
UK x18

Sorry, I mean last dose RNS 90 days prior

I guess hey are not going to break the randomisation blinding until after the last patient has had 90 days after first dose. So we should get a RNS 90 days prior to 1 October??

Seems like a total delay from previous plan is 1 month. Would have been 6weeks but they have pinched 2 weeks with rewording.

If they break the blinding on 1 Oct and there is anything like similar stats to P2, they will go straight for EUA IMHO

Sorry everyone, it seems they have done two things, one good, one bad

Primary completion and study completion dates are BOTH now 1st October. That’s one month after the original Study completion. And 4 months after previous primary completion.

Good news is that study completes 90 days after FIRST dose (of last patient), was previously 90 days after last dose of last patient.

Many more sites announced!

AJ, IF that were true, I imagine they would include SNG001. It's British, has great safety data and seems to have the most positive treatment effect of all tested meds to date. That would be RNSable immediately if it lands. They may buy it conditional on a positive/safe readout at P3 but still RNSable.

Agreed Oak, RM a new man in the radio interview than the HT interview. Totally regained his presence as a leader that we had been accustomed to prior to HT

For the record Breathlessness, Cough and Sputum Score (BCSS) has been around for longer than I said. It was proposed and validated in 2003. Cited 36 times.

https://pubmed.ncbi.nlm.nih.gov/14665499/

Yes Doc ACTIV2 is our play and I agree with what MikeP hints that RM may be unable to speak about ACTIV2 at present as an RNS is imminent. He did say they are searching for research groups around the world to focus on out-patient treatment of grade 3/4 breathlessness on BCSS.

My money is on SNG001 progressing to P3, ACTIV2 and that they are knee-deep in a battle to only recruit those grades of breathlessness within it. They Americans will hopefully concur, though they state the ACTIV2 plan is to include the P2 patients in the count for P3 ACTIV2. In other words, we would start with 110 recruited in any extension to P3. Given that another circa 890 to be recruited (as per Dr Castro's estimate, to be firmed up by a power calculation after P2 read), P2 shouldn't dilute our overall signal much in the end IF we can persuade the Americans of the validity of our science on breathlessness. I think we will win that one. So excited by the interview this morning. The market seems to be picking up on positive sentiment.

Dumb, they are using the same outcomes as the other researchers - called the Ordinal Scale for Clinical Improvement (OCSI), which is the one the WHO tells everyone to use. It The BCSS is only for categorising the health of those entering the trial, which is great as it has led to us finding this subset that get helped the most both in the community and in hospital.

Yes Doc, if Synairgen aren't knocked out of ACTIV2 at the end of P2 they will hopefully find they're pushing at an open door when they ask only to do Marked or Severe Breathlessness patients for P3 of ACTIV2. The nature of science is that knowledge is gained by research and our HT, despite shaking out a whole pile of PIs, has taught us so much that is priceless going forward. It is invaluable to know that we should be treating based on breathlessness rather than our best bet prior to the HT, which was assumed to be those at "high risk" - over 65 or under 65 with "relevant" co-pathologies.

It's a bit close to call if we will have a sufficient signal in these low and high risk out-patients in ACTIV2 for us to get selected to continue to P3. If we do, I'm sure they will tailor the protocol to the breathlessness above. Now that is a study worth doing! I personally think we have a good chance as it will progress if it shows a 30% reduction in hospitalisations compared to placebo. This will hopefully be seen but numbers tiny so a bit random to be sure yet. I was mildly concerned that RM didn't mention ACTIV2 in this interview.

If we get into P3 of ACTIV2, that is certainly worth a good few 10s of millions of dollars of free research and in my opinion will greatly help the SP

Sorry misprint , its BCSS

It has been around, validated and used since at least 2013. It was pre-selected as the tool of choice at protocol writing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594703/

Hi Doc, they used the Breathlessness, Cough and Sputum Scale (BCCS)

a. Breathlessness scoring system from the Breathlessness, Cough and Sputum Scale (BCSS)
How much difficulty did you have breathing today?
0 = None – unaware of any difficulty
1 = Mild – noticeable when performing strenuous activity (e.g. running)
2 = Moderate – noticeable even when performing light activity (e.g. bedmaking or carrying groceries)
3 = Marked – noticeable when washing or dressing
4 = Severe – almost constant, present even when resting

It was the last two categories, marked and severe breathlessness, that they are now focussing on.

Yes Meelie, as you say, the page was written on 19th March. Now I am much more encouraged. The first Sprinter trial recruit anywhere was on 13th Jan. Meaning Bournemouth had managed 12 recruits in the first 2 months of recruitment. Another 2 months have now passed, albeit with much less COVID incidence, so hopefully well beyond 12 recruits now. Every little helps!

Noted Alpha, thanks. Good to use the correct terminology. Agreed, the only hospital patients in USA will be inside Synairgen's SPRINTER P3

I think all were recruited in Bournemouth.

https://www.uhd.nhs.uk/services/research-and-innovation/rbch/covid-19-research

From the Dorset NHS page saying they are working closely with colleagues in Bournemouth, "12 patients have been enrolled so far." Encouraged to hear that

Yes Alphageddon, that is what I had intended, progress to phase 3 within the ACTIV2 (sorry if that isn't called ACTIV3, I'm learning!)

Matterhorn, I nteresting paragraph about graduating from ACTIV2 to ACTIV3 in the link you sent of the protocols

"Hospitalization/Death: Although there will be very limited precision to compare an investigational agent to placebo in Phase II, graduation may also be considered based on hospitalization/death if the proportion of participants who are hospitalized or die by day 28 is lower by 33.3% (specifically, one-third) for an investigational agent versus placebo (i.e., X in the probability statement above is a relative reduction of 33.3% for this outcome)."

By this standard, our home trial data would have been waved through. 2 hospitalised on placebo, none on SNG001. Though not a secure place to be statistically, as so close to zero in each arm and small numbers so certainly not statistically significant, those data would have been enough.

Fingers crossed we progress. Especially if we can persuade the Americans to focus on marked or severe breathlessness patients for ACTIV3??