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

A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of the Oral Factor D (FD) Inhibitor ACH-0145228 in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy and with an Approved C5 Inhibitor as Background Therapy

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003830-17-IT

Enrollment

Registered

2020-06-23

Start date

2021-10-13

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Interventions

Product Name: ALXN2050 Product Code: ACH-0145228 Pharmaceutical Form: Capsule INN or Proposed INN: N/A CAS Number: 2086178-00-7 Current Sponsor code: ALXN2050 Other descriptive name: ACH-0145228 Conc

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 1

Exclusion criteria

Exclusion criteria: - 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.

Design outcomes

Primary

Measure	Time frame
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 • To evaluate the efficacy of ACH-0145228 on lactate dehydrogenase (LDH) relative to baseline at Week 12 of treatment • To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH) • 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	—

Measure

Time frame

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 • To evaluate the efficacy of ACH-0145228 on lactate dehydrogenase (LDH) relative to baseline at Week 12 of treatment • To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH) • 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

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Secondary

Measure	Time frame
Secondary end point(s): 1.Transfusion requirements: Change in transfusion requirements during the treatment compared to 12 weeks of historical transfusion requirements 2. Lactate dehydrogenase (LDH): Change in LDH relative to baseline at Week 12 3. Reticulocyte count: Change from baseline in absolute reticulocyte count 4. Direct Bilirubin: Change from baseline in direct bilirubin 5. Total Bilirubin: Change from baseline total bilirubin 6. PNH red blood cell (RBC) clone size: Change from baseline in PNH red blood cell (RBC) clone size 7. C3 complement protein (C3) fragment deposition on PNH RBCs: Change from baseline in C3 complement protein (C3) fragment deposition on PNH RBCs at week 12 8. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Number of TEAEs recorded 9. Incidence of Serious Adverse events [Safety and Tolerability]: Number of SAEs recorded 10. Incidence of adverse events leading to discontinuation [Safety and Tolerability]: Number of events leading to discontinuation of study medication recorded ;Timepoint(s) of evaluation of this end point: at Week 12	—

Measure

Time frame

Secondary end point(s): 1.Transfusion requirements: Change in transfusion requirements during the treatment compared to 12 weeks of historical transfusion requirements 2. Lactate dehydrogenase (LDH): Change in LDH relative to baseline at Week 12 3. Reticulocyte count: Change from baseline in absolute reticulocyte count 4. Direct Bilirubin: Change from baseline in direct bilirubin 5. Total Bilirubin: Change from baseline total bilirubin 6. PNH red blood cell (RBC) clone size: Change from baseline in PNH red blood cell (RBC) clone size 7. C3 complement protein (C3) fragment deposition on PNH RBCs: Change from baseline in C3 complement protein (C3) fragment deposition on PNH RBCs at week 12 8. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Number of TEAEs recorded 9. Incidence of Serious Adverse events [Safety and Tolerability]: Number of SAEs recorded 10. Incidence of adverse events leading to discontinuation [Safety and Tolerability]: Number of events leading to discontinuation of study medication recorded ;Timepoint(s) of evaluation of this end point: at Week 12

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Countries

Italy, Korea, Republic of, New Zealand, Spain, United Kingdom, United States

Contacts

Public ContactEuropean Clinical Trial Information

Alexion Europe SAS

clinicaltrials.eu@alexion.com+33147100615

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026