Study of the Oral Factor D (FD) Inhibitor ALXN2050 in PNH Patients as Monotherapy

NCT04170023 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ACH228-1102019-003830-17
• Study Type: interventional
• Target: 29
• Locations: 7 countries
• Sites: 11

Brief Summary

The study will evaluate the efficacy and safety of the oral Factor D (FD) inhibitor ALXN2050 (ACH-0145228) monotherapy in patients with PNH that are treatment naïve, or patients currently treated with eculizumab who still experience anemia and reticulocytosis, or patients currently treated with ALXN2040 (danicopan) as monotherapy. After signing consent, participants will have periodic visits through Week 12, at which time the primary endpoint and key secondary assessments will be analyzed. Participants will continue on treatment past 12 weeks into a long-term extension portion of the trial.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

paroxysmal nocturnal hemoglobinuria; PNH; extravascular hemolysis; EVH; factor D inhibitor; complement; C5 inhibitor; danicopan

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hgb at Week 12

  Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. To address the impact of transfusion, Hgb values collected within 4 weeks after transfusion were not included in the primary efficacy analysis. Change from Baseline = Hgb at Week 12 - Baseline Hgb.

  Baseline, Week 12

Secondary Outcomes (13)

• Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050

  Baseline up to Week 12

• Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment

  Baseline up to Week 12

• Number of Transfusion Instances During 12 Weeks of Treatment

  Baseline up to Week 12

• Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12

  Baseline, Week 12

• Change From Baseline in Absolute Reticulocyte Count at Week 12

  Baseline, Week 12

Study Arms (1)

Open-label ALXN2050 Monotherapy

EXPERIMENTAL

Experimental: Open-label ALXN2050 Monotherapy ALXN2050 orally administered Group 1: Patients with PNH who are treatment naïve Group 2: Patient with PNH who have received complement component 5 (C5) inhibition with eculizumab for at least 6 months, who continue to experience anemia and reticulocytes above the upper limit of normal (ULN) Group 3: Patients with PNH who have received danicopan monotherapy during study ACH471-103

Drug: ALXN2050

Interventions

ALXN2050 DRUG

Oral FD inhibitor

Also known as: ACH-0145228

Open-label ALXN2050 Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PNH.
• Male or female, ≥ 18 years of age
• Eligibility Criteria:
• Eligibility Criteria Specific for Group 1:
• PNH Patients who have no history of treatment with any complement inhibitor at any dose.
• PNH Type III erythrocyte or granulocyte clone size ≥10%
• Absolute reticulocyte count ≥100×10\^9/liter \[L\].
• Anemia (Hgb \<10.5 grams/deciliter \[g/dL\]).
• LDH ≥1.5× upper limit of normal.
• Platelet count ≥30,000/microliter (µL)
• Absolute neutrophil count (ANC) ≥750/ µL.
• Eligibility Criteria Specific for Group 2:
• Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks
• Anemia (Hgb \<10 g/dL)
• Absolute reticulocyte count ≥100×10\^9/L

You may not qualify if:

• History of a major organ transplant or hematopoietic stem cell/marrow transplant .
• Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents for less than 24 weeks.
• Known underlying bleeding disorders or any other conditions leading to anemia not primarily associated with PNH.
• Estimated glomerular filtration rate \<30 milliliters/minute/1.73 meters squared and/or are on dialysis.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (11)

Research Site

Toronto, Ontario, M5G2C4, Canada

Location

Research Site

Lévis, Quebec, G6V 3Z1, Canada

Location

Research Site

Avellino, 83100, Italy

Location

Research Site

Florence, 50134, Italy

Location

Research Site

Christchurch, 8011, New Zealand

Location

Research Site

Grafton, 1010, New Zealand

Location

Research Site

Seoul, 06591, South Korea

Location

Research Site

Albacete, 02006, Spain

Location

Research Site

Istanbul, 34093, Turkey (Türkiye)

Location

Research Site

Izmir, 35100, Turkey (Türkiye)

Location

Research Site

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Kulasekararaj AG, Browett PJ, Risitano AM, Patriquin CJ, Yenerel MN, Marceau D, Sahin F, Algarra L, Ogawa M, Yu J, Cross N, Notaro R, Lee JW, Brodsky RA. Efficacy and Safety of Vemircopan as Monotherapy in Patients With Paroxysmal Nocturnal Hemoglobinuria. Blood Adv. 2025 Oct 22:bloodadvances.2025017731. doi: 10.1182/bloodadvances.2025017731. Online ahead of print.

  PMID: 41124654 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemolysis

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 20, 2019
• Study Start: December 16, 2019
• Primary Completion: April 27, 2023
• Study Completion: March 20, 2024
• Last Updated: November 20, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

TU (2); GB (1); ES (1); CA (2); KR (1); NZ (2); IT (2)