302-Phase 3 study of ALXN1210 VS ECULIZUMAB in adult patients with PNH
Research type
Research Study
Full title
A PHASE 3, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED STUDY OF ALXN1210 VERSUS ECULIZUMAB IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA (PNH)CURRENTLY TREATED WITH ECULIZUMAB
IRAS ID
213114
Contact name
Austin Kulasekararaj
Contact email
Sponsor organisation
Alexion Pharmaceuticals
Eudract number
2016-002026-36
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
128367, IND number
Duration of Study in the UK
2 years, 11 months, 26 days
Research summary
Research Summary
The purpose of this study is to evaluate how safe and effective study drug ALXN1210 is compared to the active labelled drug eculizumab, when administered by intravenous (IV) infusion to adult patients with PNH. These patients must be clinically stable having been treated with the labelled dose of eculizumab for at least 6 months prior to receiving study drug. PNH is a condition caused by an abnormality that causes destruction of red blood cells. Eculizumab, is approved for the treatment of PNH in 46 countries under the brand name Soliris® and is the current standard of care treatment for those with PNH.
ALXN1210 is being developed for the treatment of disorders involving the complement system. The complement system is a part of the complex immune system (system that fights against infections). ALXN1210 works by suppressing the activity of a specific portion of the complement system; it is therefore classified as an immunosuppressant drug. PNH is an example of a complement disease that could be eventually treated with ALXN1210.
There will be 3 periods in this study. A 4 week Screening Period, 26 week Randomised treatment Period in which patients will be randomly assigned to one of 2 treatment groups to receive either ALXN1210 or eculizumab and finally a 2 year Extension Period in which all patients will receive ALXN1210. The duration of participation in the study is approximately 2.5 years. The study drug will be administered intravenously into a vein and blood samples will be collected throughout the study for various analysis either prior to, or after, study drug administration.
It is expected that approximately 125 centres will be opened globally in order to enrol 192 participants for evaluation.
Summary of Results
This clinical study report (CSR) presents data through the end of the 26-week Randomized Treatment Period, referred to as the Primary Evaluation Period, as well as all available long-term data for patients who received ravulizumab treatment during the Extension Period through the end of the study.
In total, 197 eculizumab-experienced patients with PNH were randomized in the study and
195 patients treated with ravulizumab (N = 97) or eculizumab (N = 98); 191 patients completed the Primary Evaluation Period. One patient in the ravulizumab group did not complete the Primary Evaluation Period due to patient decision to withdraw from the study, and 3 patients in the eculizumab group did not complete due to patient decision to withdraw, lack of efficacy, and pregnancy (1 patient each). All patients in both treatment groups received all planned infusions during the Primary Evaluation Period.
Eleven patients withdrew from the study during the Extension Period; 6 patients due to physician decision, 3 patients died, 1 patient was lost to follow-up, and 1 patient due to patient decision.
The favorable benefit/risk profile of ravulizumab in this study demonstrates that patients with PNH may be safely and effectively switched from eculizumab to ravulizumab.
Primary Evaluation Period
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For the primary endpoint and all 4 key secondary efficacy endpoints, ravulizumab achieved statistically significant noninferiority compared to eculizumab, with treatment differences consistently favoring ravulizumab.
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Compared to eculizumab, ravulizumab provided better disease control as evidenced by complete and sustained inhibition of terminal complement throughout the entire 26-week treatment period with no events of BTH.
Ravulizumab Treatment
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Disease control achieved during the initial 26 weeks of ravulizumab treatment was maintained up to 4 years of ravulizumab treatment.
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Ravulizumab treatment resulted in complete terminal complement inhibition as evidenced by free
C5 levels below 0.5 µg/mL in all patients at all times.
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The frequency of BTH events over time during ravulizumab treatment in the Extension period was consistent with the known profile of ravulizumab.
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Ravulizumab continued to be well tolerated and demonstrated the same benefit risk profile through the Extension Period as observed during the Primary Evaluation Period.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
17/EE/0124
Date of REC Opinion
30 May 2017
REC opinion
Further Information Favourable Opinion