Study of the Oral Factor D (fD) Inhibitor ACH-0145228 in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy and with background use of an Approved C5 Inhibitor
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria (PNH)MedDRA version: 21.1Level: PTClassification code 10034042Term: Paroxysmal nocturnal haemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-003830-17-GB
- Lead Sponsor
- Achillion Pharmaceuticals, Inc., a wholly owned subsidiary of Alexion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 26
Male or female greater than or equal to 18 years of age, female subjects of child-bearing potential
For newly identified PNH patients must meet one of the following conditions:
1. PNH patients not currently receiving an approved C5 inhibitor must have:
- PNH Type III erythrocyte and/or granulocyte clone size =10% with adequate reticulocytosis (absolute reticulocyte count =100×10?/L).
- Anemia (Hgb <10.5 g/dL).
- LDH =1.5× upper limit of normal (ULN).
- Platelet count =30,000/µL without the need for platelet transfusions.
- Absolute neutrophil count (ANC) =750/ µL.
2. PNH patients with a sub-optimal response to background therapy with an approved C5 inhibitor must have:
- Stable background regimen of an approved C5 inhibitor (at least 24 weeks for eculizumab, or at least 2 doses for ravulizumab), without change in dose or interval for at least the past 8 weeks.
- Anemia (Hgb <10 g/dL).
- Adequate reticulocytosis (absolute reticulocyte count =100×109/L).
Platelet count =30,000/µL without the need for platelet transfusions.
- Absolute neutrophil count (ANC) =750/ µL.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 and/or are on dialysis.
- History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant ([HSCT] unless HSCT engraftment has failed).
- History of dosing with an investigational agent other than danicopan within 30 days or 5 half-lives of the investigational agent prior to ACH 0145228 administration, whichever is greater.
- New patients in the monotherapy group with a history of dosing with eculizumab at any dose or interval within the past 75 days before study medication administration or 300 days for ravulizumab.
- Known or suspected complement deficiency.
- Contraindication to one or more of the required vaccinations that may be used in the study.
- History of seizure disorder unless seizure free without the use of antiepileptic medications for the past 5 years prior to screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of ACH-0145228 based on improvement hemoglobin (Hgb) relative to baseline at Week 12 of treatment;Secondary Objective: • To evaluate the efficacy of ACH-0145228 based on reduction in transfusion requirements<br>• To evaluate the efficacy of ACH-0145228 on lactate dehydrogenase (LDH) relative to baseline at Week 12 of treatment<br>• To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH)<br>• To evaluate the safety and tolerability of 12 weeks of treatment with ACH-0145228 with or without the use of background therapy with an approved C5 inhibitor, based on treatment-emergent adverse events, (TEAEs), serious adverse events (SAEs), and events leading to discontinuation of study medication;Primary end point(s): Change in Hgb relative to baseline at Week 12;Timepoint(s) of evaluation of this end point: at Week 12
- Secondary Outcome Measures
Name Time Method