Phase 3 Luspatercept Trial

Hi everyone! I didn't see any threads about the new Luspatercept trial so I figured let me pass some info. along and get a discussion going since I am so excited. Recently Acceleron and Celgene announced they are ready to progress their Luspatercept program into Phase 3 Clinical trials. This means once this trial is over and the results are good they can submit to the FDA for drug approval.

Recap: Luspatercept is a subcutaneous injection given once every 3 weeks to help reduce the blood transfusion burden in thalassemia patients. Phase 2 results have been excellent with minimal side effects and all evaluable patients showing greater than 40% reduction in blood transfusion requirement (transfusion dependant patients).

The phase 3 trial is titled the "BELIEVE" trial and is scheduled to start by the end of this year, 2015. Patients who are regularly transfused (8-20 units per 24 weeks) will be eligible to participate. 200 patients will receive luspatercept 1 mg/kg SubQ while 100 patients will receive placebo (non-active injection). Neither patient nor investigator will know who is receiving drug or placebo. The trial is therefore random and double-blinded.

No details yet on where the trial will be offered but I have been told it is a global trial. Stay alert for more updates. If any one has any further to add please do so

I can't see why a double blind trial is being used. It's not like a placebo effect is going to raise the Hb level.

I can't see why a double blind trial is being used. It's not like a placebo effect is going to raise the Hb level.

I absolutely agree with you. I think it complicates things and adds undue harm to the placebo recipient since they will wait for hgb to drop to a specific level before transfusing most likely 1 unit at a time. There will be at least weekly cbc to monitor hgb. For 48 weeks for a patient to get placebo and undergo all this is tortourous (being a patient myself).

The only logic I can see in a placebo trial is to compare side effects. If placebe thalassemia patients complain of headache and bone pain more so than the general population it may help to discredit these side effects being attributed to the drug itself. I can't imagine why a patient would stick it out for 48 weeks when one would realize by week 5-6 that obviously the drug isn't being administered since blood requirement would remain the same and quality of life worse than before.

All good points. And something expressed to me is that not knowing if they're getting the drug is keeping patients from joining trials.

I have been waiting to enrol lil A in this trial for a long time.  I understand why it may be helpful to make this trial double blind, but for my son - who has an antibody which is active some times and not others - his participation in the study may skew the results of the study is conducted double blind.  His results can only be compared to himself - how he did in a given year with and without luspatercept. 

I have been waiting to enrol lil A in this trial for a long time.  I understand why it may be helpful to make this trial double blind, but for my son - who has an antibody which is active some times and not others - his participation in the study may skew the results of the study is conducted double blind.  His results can only be compared to himself - how he did in a given year with and without luspatercept. 

Hi Sharmin, how old is your son? I hope the trial is flexible and gets under way quickly.

Hello CrazyPharm,

I agree, this medication, if it turns out to be what it seems will improve the quality of life of thals. 

My son is 17. I think participants are required to be 18+ years of age.

Where are these trials conducted.

Sharmin,

Little A is now 17, amazing, how fast they grow. I remember talking about him on the forum when he was six (I believe). You certainly have done an excellent job.

The trials will be conducted at multiple centres Canadian Family.  Oakland may be involved in the study.  I will keep you posted.  By next year all of our kids may have the option to be on this medication which may eliminate or greatly reduce their transfusion requirement. 

Time has passed by so quickly.  Lil A is preparing for university.  I hope lil miss A is doing well also.

Hoping for the best,

Sharmin

Thanks for the information. Good Luck to young man, wishing him best of luck in everything.

Little Miss A is 12 now and in grade 7. She is a happy kid and interested in arts.

Glad to hear that Canadian Family!

Celgene and Acceleron Announce New Results from an Investigational Study with Luspatercept in Beta-Thalassemia Presented at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition

SUMMIT, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG) and Acceleron Pharma Inc. (NASDAQ:XLRN) today announced preliminary results from two Phase 2 clinical trials of luspatercept in patients with beta-thalassemia were presented at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition. Results highlighted in an oral presentation showed that luspatercept increased hemoglobin levels, reduced transfusion burden, improved health-related quality of life measures and had beneficial effects on liver iron concentration in patients with beta-thalassemia. Celgene and Acceleron are jointly developing luspatercept.

"These luspatercept results are very exciting as they show positive effects across a range of clinically challenging complications of beta-thalassemia," said Professor Antonio Piga, M.D., Ph.D., Director of Pediatrics at San Luigi Gonzaga University Hospital in Torino, Italy and coordinating principal investigator of the study. "A therapy that could potentially treat the anemia, complications of beta-thalassemia, such as iron overload, and improve measures of health-related quality of life would be a huge advance to help address the substantial unmet need of patients with beta-thalassemia."

Luspatercept Data Presented at ASH

Luspatercept was evaluated in a Phase 2, multicenter, open-label study in adults with non-transfusion-dependent (NTD) and transfusion-dependent (TD) beta-thalassemia patients. The primary objectives were to assess the proportion of NTD patients that achieved a hemoglobin increase ≥ 1.5 g/dL from baseline and the proportion of TD patients that achieved at least a 20% reduction in transfusion burden. A total of 64 patients, of which 59 were efficacy evaluable (31 NTD and 28 TD), were enrolled in the dose escalation and expansion stages of the Phase 2 clinical trial. In this study, patients received up to 5 doses via subcutaneous injection once every 3 weeks. 51 of the 64 patients from this 3-month study enrolled in the long-term Phase 2 extension trial in which these patients may receive up to two years of treatment with luspatercept. Data was presented from both the 3-month study and the long-term extension study.

Improvement of anemia and transfusion burden:

Of the 17 NTD patients that received at least 5 cycles of luspatercept at dose levels of 0.8 mg/kg or higher
65% (11/17) increased hemoglobin levels ≥ 1.0 g/dL over a 12-week period
47% (8/17) increased hemoglobin levels ≥ 1.5 g/dL over a 12-week period
Data presented showed sustained increases in hemoglobin with the longest-treated patients having received nearly six months of luspatercept
Of the 28 TD patients
79% (22/28) patients had ≥ 20% reduction of transfusion burden
75% (21/28) patients had ≥ 33% reduction of transfusion burden
57% (16/28) patients had ≥ 50% reduction of transfusion burden
Changes in iron overload:

Liver iron concentration (LIC), a measure of iron overload, was maintained or reduced in both non-transfusion dependent and transfusion-dependent patients
50% (4/8) TD patients with baseline LIC ≥ 5 mg/g dry weight (dw) had decrease in LIC ≥ 2 mg/g dw
100% (14/14) TD patients with baseline LIC &#60 5 mg/g dw maintained LIC &#60 5 mg/g dw
36% (5/14) NTD patients with baseline LIC ≥ 5 mg/g dw had decrease in LIC ≥ 2 mg/g dw
100% (14/14) NTD patients with baseline LIC &#60 5 mg/g dw maintained LIC &#60 5 mg/g dw
Improvement in health-related quality of life (QoL) measures in NTD patients:

Improved health-related QoL (FACT-An anemia subscore) correlated with increases in hemoglobin in NTD Patients
Safety:

The most common related adverse events were bone pain, myalgia, headache, arthralgia, musculoskeletal pain, asthenia, injection site pain, back pain and pain in jaw
Related grade 3 adverse events included headache, bone pain, asthenia, and myalgia
There were no drug-related serious adverse events
Celgene and Acceleron are in the process of initiating a global Phase 3 study in regularly transfused beta-thalassemia patients.

Luspatercept is an investigational product that is not approved for any use in any country.

thanks Parin for the update!!

these are very good results...hope this becomes available to patients soon...

Dec 30th and still not started... tsk tsk

wat is the procedure and requirement to be a part of this trial ??