Plain Language Summary
What is this summary about?
This plain language summary describes the phase 3 PRINCE study. The study looked at adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder that is acquired (not inherited), usually during adulthood. PNH causes hemolysis, which is the destruction of red blood cells. The PRINCE study compared a new medicine, pegcetacoplan, with the older treatment of supportive care (includes red blood cell blood transfusions; blood thinners; steroid medicines; and supplements, like iron, folate or vitamin B12). Supportive care was the standard treatment worldwide until eculizumab, the first C5 complement inhibitor medicine, was approved by the United States Food and Drug Administration and the European Medicines Agency in 2007 for the treatment of PNH. Supportive care is still the standard treatment for PNH in countries where C5 complement inhibitor medicines are not available. The PRINCE trial aimed to show if pegcetacoplan reduced hemolysis and if side effects occurred with pegcetacoplan in patients who had not received C5 complement inhibitor medicines recently.
How was the study carried out?
Participants were adults with PNH and anemia. Anemia was defined as a hemoglobin level of less than 13.6 grams per deciliter of blood for men and less than 12.0 grams per deciliter of blood for women. Hemoglobin is a protein inside red blood cells. Participants in the trial had not recently been treated with a C5 complement inhibitor medicine (eculizumab or ravulizumab). The participants were split into 2 groups: a pegcetacoplan group and a supportive care group. 35 participants received pegcetacoplan for 26 weeks, and 18 participants received supportive care. Those who received supportive care could switch to pegcetacoplan if their anemia got worse. Researchers monitored the participants' blood markers for hemolysis, how participants felt during the trial and the participants' side effects. The study started in 2019 and ended in 2021.
What were the results?
Participants who received pegcetacoplan had fewer signs of hemolysis after 26 weeks of treatment with pegcetacoplan compared with participants who received supportive care. Although participants in both groups had side effects, most were not serious. No serious side effects were related to pegcetacoplan.
What do the results show?
These results show that pegcetacoplan reduced hemolysis in adults with PNH better than supportive care. None of the side effects related to pegcetacoplan were serious. Results from the PRINCE study were published in Blood Advances in 2023.
Clinical Trial Registration: NCT04085601 (PRINCE) (ClinicalTrials.gov)
Tweetable abstract
In the PRINCE study, adults with paroxysmal nocturnal hemoglobinuria (PNH) who had not recently taken a C5 complement inhibitor medicine received pegcetacoplan or supportive care. Pegcetacoplan reduced hemolysis better than supportive care and was well tolerated.
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Financial disclosure
RSMW has received consulting fees, honoraria, research funding and speaker's bureau fees from Alexion and F. Hoffmann-La Roche Ltd, and research funding and speaker's bureau fees from Apellis Pharmaceuticals, Inc. DGA has served in speaking and advising roles from Teva, Roche, Amgen, Bristol Myers Squibb, Takeda, Janssen, AbbVie and Astellas. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Ethical conduct of research
The study protocol was designed and monitored in accordance with the ethical principles of Good Clinical Practice and the Declaration of Helsinki. An institutional review board or independent ethics committee at each center approved the protocol. Each patient provided written informed consent before undergoing study-related procedures.
Data sharing statement
To request access to data from the PRINCE trial or the study protocol, please contact [email protected]. The study protocol will be available with no end date. All proposals requesting data access will need to specify how the data will be used and will need the approval of the trial investigator team before data release. Individual participant data will not be shared.
Acknowledgments
All authors contributed to manuscript development and reviewed and approved the content of the submitted manuscript. Acknowledgments Thank you to the study participants, their caregivers, the institution staff and the study investigators for their participation in and valuable contributions to the PRINCE study. Participants in clinical studies belong to a community of people who take part in clinical research around the world. They help researchers answer important health questions and find medical treatments for patients.
Competing interests disclosure
MAA, TA and JS were employees of Apellis Pharmaceuticals, Inc., at the time of the study. PD, CF and FG are employees and current equity holders of Apellis Pharmaceuticals, Inc. PA is a former consultant for Apellis Pharmaceuticals, Inc. JRNC, NSC, YTG, DK and TD declare no competing interests. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing disclosure Additional writing and editing assistance, including preparation of a draft plain language summary under the direction and guidance of the authors, incorporation of author feedback and submission, was provided by Kathryn Fogarty, PhD (Kay Square Scientific, Newtown Square, PA, USA) and Catherine Champagne, PhD (Kay Square Scientific, Newtown Square, PA, USA). This support was funded by Apellis Pharmaceuticals, Inc.