New trial with Kalydeco and splicing/residual function mutations

G

GenH

New member
Big news- new phase 2 study looking at Kalydeco and CFTR Mutations associated with residual CFTR function or defective mRNA splicing:

R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G, 621+1G->T

http://clinicaltrials.gov/ct2/show/NCT01685801?term=vx-770&rank=19

I believe with gating, plus residual function and splicing, this could be 20% of the CF population.

It also mentions open label at the end which is excellent for a phase 2 trial.
 
C

cftrsplicing

New member
Double post (http://forum.cysticfibrosis.com/threads/35614).
Anyway great news.
I think this will open the doors to test it on more and more mutations.
I believe stop mutations too (class I) can have some benefit by Ivacaftor. Especially if the stop codon happens after R Domain. And I hope investigators will expand research even on those.

A target easily reachable is Atypical CF or CF Related. Tg12 and 5T polymorphisms decrease splicing efficiency of wild type. They should investigate on these too.

Anyway at the moment, great great news.
 
G

GenH

New member
Yes I did just see your post, but often its hard to find a post within a separate topic if its not mentioned in the heading! I agree that there are other mutations that may show an improvement as well. It would also be interesting to look at Ataluren and Kalydeco together with nonsense mutations.
 
J

JENNYC

New member
Does anyone know what is going on with Ataluren? I haven't seen anything in a while. Abby has a class 1 stop codon and it is helping her, not to the extent it is helping G551D but I will take it, and I am thinking that the Ataluren will further help her, but I haven't heard one word about it. And seeing how her Dr didn't want her on Kaly I can't see him offering any info he knows on Ataluren. So I think it's up to me to find out, which is scary :)
 
T

triples15

Super Moderator
Gen H, Thanks SOO much for posting this! I really appreciate you taking the time to post all the great info that you do!

I have S945L and have been hoping and hoping that would open this study up to these additional mutations. The research coordinator at my clinic told me it was a possibility but I figured it was unlikely. She told me Vertex had contacted them in regards to their patients with these mutations. She told me she would let me know if this happened but I have not heard from her yet. It looks like they are only recruiting 18 people, so even if my clinic is participating it seems unlikely that I will get in. It certainly won't hurt to try! I'm gonna email the research coordinator tonight!

Thanks again,

Autumn
 
W

welshwitch

Guest
That's me too! I'm totally confused as to how to get involved--email your doctor? Ask them?
 
D

dramamama

New member
Hey Guys!
I would really encourage any of you with any of these mutations to try and get in the trial. It is a quick trial and then you get the drug....

From the researcher doing the trial:
People can call Connie St. Clair directly at 303-270-2517.
It really is open to people from around the country, if they have a fair
amount of flexibility in their schedules- Vertex pays for travel.

They are the only center doing the trial. GET ON IT!
 
C

cfsucks

Guest
sweet!

why is it planned to take a year though? and will they have to do 3 phases? or just prove it's effective?

also im in canada- any chance i can get in on the study?
 
J

Julie7

New member
Cftrsplicing
Are you talking about 5T 12TG polymorphisms alone OR paired with another CF causing mutation?
 
T

triples15

Super Moderator
I called Connie first thing this morning and left a voice mail. Haven't heard anything back yet and wondering if the study is full.......

Claire- did you try calling or have any luck?
 
T

triples15

Super Moderator
Mandy,

Have you heard of anyone having success in getting into this trial? I have called and left a message with Connie St. Clair, emailed Vertex, and talked to the research coordinator at my clinic and have gotten nowhere. Connie has not returned my call, the coordinator at my clinic says she is looking into who to contact but I have yet to hear back from her as well, and no response from Vertex. So pretty much at a standstill. I was thinking time was of the essence and every day that goes by I lose more hope that I'll get into the study. If they are only recruiting 18 people I would assume that would happen pretty quickly.

Also, there is one criteria for the study that I'm not 100% sure how to read......

Clinical evidence of residual CFTR function based on any 1 of the following: 1)Clinically documented residual exocrine pancreatic function, 2)Sweat chloride value ≤80 mmol/L at screening, or 3) Age of diagnosis ≥12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing

What do you take "age of diagnosis" to mean? That you were diagnosed over 12 years ago? Or do they mean age AT diagnosis? I was only 3 months old at diagnosis so if that's what they are asking I do not meet the criteria and don't need to continue stressing about how to get into the study.

Thanks in advance if anyone has any insight!

Autumn
 
G

GenH

New member
Clinical evidence of residual CFTR function based on any 1 of the following: 1)Clinically documented residual exocrine pancreatic function, 2)Sweat chloride value ≤80 mmol/L at screening, or 3) Age of diagnosis ≥12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing

I interpret this to mean that you have to have 1 CFTR mutation assoicated with residual CFTR function or defective mRNA splicing as well as 1 of the three clinical criteria- either residual exocrine pancreatic function, sweat chloride equal or less than 80 and diagnosis over or at the age of 12.
 
A

Aboveallislove

Super Moderator
GenH: I actually interpretted it as any one of the three--you don't have to necessarily have 1 cftr mutation associated with residual function/defective splicing, if you meet the other criteria.
 
C

cftrsplicing

New member
Yes it means Any of those 3 criteria.
StClair answered me back via mail and said that recruitment will go on for 6 months. Study is not full.
What do you think about next? Will there be a phase III study involving all residuals? or will this be enough to expand labels?
Will a 20mmol decrease in sweat chloride or a 10-15% relative improvement in FEV1 Enough?
 
G

GenH

New member
aboveallislove- I would be surprised if that was the case given that it says and (and also lists a lot of mutations), but I may be wrong! Given that they only need 18 it would make sense to get people with genetic evidence (less risky for their trial results), but I have not spoken to the researchers so I'm not sure.

cftrsplicing- Do you have to have 1 of the three criteria plus evidence of a gene associated with residual function/splicing or do you just have to have one of the three criteria (and genes dont matter)?

It will be interesting to see if the phase 2 is sufficient for FDA listing, my guess is that a phase 2 would not be sufficient for markets such as Australia (unsure about the listing process on other health systems).

A small increase might be enough to get through if the cost is cheap enough!!
 
T

triples15

Super Moderator
Thanks everyone!

It's looking like perhaps I don't meet the criteria for the study. Serves me right for not taking to time to read and comprehend everything! I got so carried away with excitement when I saw my mutation was included that I guess I didn't process everything! I do have one residual function mutation (S945L), but I was diagnosed at 3 months, my sweat tests were 82 and 105 (if memory serves correct), and I am technically PI (although require few to no enzymes). So.....I don't think I meet the criteria. Blah.

Thanks cfstrsplicing! I'm glad St. Clair answered your email. I'm surprised the recruitment phase will go on for 6 months. I guess when I heard they were only recruiting 18 people I figured it would be quick. I should have known that these things always take time! Are you looking to participate in the trial?

Thanks again everyone!
 
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