Study of the Oral Factor D (FD) Inhibitor ALXN2050 in PNH Patients as
Research type
Research Study
Full title
A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of the Oral Factor D (FD) Inhibitor ALXN2050 (ACH-0145228) in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy
IRAS ID
285888
Contact name
Austin Kulasekararaj
Contact email
Sponsor organisation
Alexion Pharmaceuticals Inc.
Eudract number
2019-003830-17
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
U1111-1241-2441, WHO UTN
Duration of Study in the UK
3 years, 5 months, 9 days
Research summary
PNH is a disease caused by genetic mutations (changes to the genes in your body) that lead to the destruction of red blood cells (RBCs), can cause anemia (too few RBCs) and may also cause unwanted clotting (thickening) of the blood.
Many diseases are associated with either not enough control of complement or too much activity of the complement system. Factor D (FD) is one of the proteins within the complement system, and the sponsor believes that blocking FD will help treat certain diseases, such as PNH. This study will determine if ACH-0145228, is safe and effective in increasing red blood cells (RBCs).
The only curative treatment for PNH is hematopoietic stem cell transplantation (HSCT) using allogeneic donors. Given the high transplant-related mortality, HSCT is generally not offered as initial therapy for most patients with classic PNH. Other supportive therapies include recombinant erythropoietin, corticosteroids, and androgens to stimulate erythropoiesis, anticoagulants to treat thrombotic complications, and immunosuppressive agents to stimulate hematopoiesis in the aplastic phase.
The only currently approved drugs to treat PNH are eculizumab or ravulizumab (in some countries). These are closely related monoclonal antibodies directed against complement C5, which prevents IVH by inhibiting formation of the terminal complement complex.
The study proposed with this application, is a Phase 2, open-label proof of concept study to assess the efficacy, safety, and pharmacokinetics of ACH-0145228 in PNH patients as monotherapy and with an approved C5 Inhibitor as background therapy for 12 Weeks. At the end of treatment (Week 12), a patient will have the option to participate in the long-term extension period.
Patients currently receiving ACH-0144471 (danicopan) in study ACH471-101, which evaluated danicopan on a background therapy of eculizumab will be eligible to participate in this study (ACH228-110). In addition, newly identified patients with PNH currently untreated with an approved C5 inhibitor, and patients with PNH on an approved C5 inhibitor, who meet the inclusion and exclusion criteria will be eligible to participate in this study.
About 26 participants will participate in this study at approximately 7-9 clinical sites worldwide. This study will last about 108 weeks and include up to 33 visits (17 to the study centre, 16 have the potential to be completed at home).
Lay summary of study results: The lay summary of the study results is available online at the following:https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.trialsummaries.com%252FStudy%252FStudyDetails%253Fid%253D14683%2526tenant%253DMT_MED_9011%2FNBTI%2F_Ea8AQ%2FAQ%2F5a116231-17ae-4648-8d8a-5b8e65372584%2F2%2FAB2pmfAvk-&data=05%7C02%7Cleicestercentral.rec%40hra.nhs.uk%7C2f01af7f3e7f483ed17008dd6d3816d6%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638786809855824802%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=1WaHxTnTPagp4sv1Pla9bf4H65xPCG%2FB9tvJSosicP4%3D&reserved=0
REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
20/EM/0190
Date of REC Opinion
16 Sep 2020
REC opinion
Further Information Favourable Opinion