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

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04170023
• Other study ID #: ACH228-110
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 16, 2019
• Est. completion date: October 30, 2026

Study information

• Verified date: May 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Experimental: Open-label ALXN2050 Monotherapy orally Group 1: Patients with PNH who are treatment naïve Group 2: Patients 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) who will switch to ALXN2050 monotherapy Group 3: Patients with PNH receiving danicopan monotherapy in study ACH471-103 will switch to ALXN2050 monotherapy After signing the informed consent form, participants will enter the screening period. During the Screening Period, eligibility and screening assessments will be performed. Screening assessments may be spread over more than one visit if necessary. At the baseline visit, screened participants who continue to meet eligibility criteria will enter the Treatment Period. The treatment phase will be followed by a long-term extension phase, where ALXN2050 will continue to be administered. Blood will be collected to assess the efficacy endpoints, such as, change in hemoglobin (Hgb), lactate dehydrogenase (LDH), and other measures of hemolysis. Safety and transfusion requirements will also be assessed. Participants will continue on treatment past 12 weeks in a long-term extension portion of the trial.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: October 30, 2026
• Est. primary completion date: April 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Diagnosis of PNH.

2. Male or female, = 18 years of age Eligibility Criteria:

Eligibility Criteria Specific for Group 1:

1. PNH Patients who have no history of treatment with any complement inhibitor at any dose.

2. PNH Type III erythrocyte or granulocyte clone size =10%

3. Absolute reticulocyte count =100×10^9/liter [L].

4. Anemia (Hgb <10.5 grams/deciliter [g/dL]).

5. LDH =1.5× upper limit of normal.

6. Platelet count =30,000/microliter (µL)

7. Absolute neutrophil count (ANC) =750/ µL.

Eligibility Criteria Specific for Group 2:

1. Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks

2. Anemia (Hgb <10 g/dL)

3. Absolute reticulocyte count =100×10^9/L

4. Platelet count =30,000/µL

5. Absolute neurophil count (ANC) =750/ µL

Eligibility Criteria Specific for Group 3:

1. Patient received danicopan during Study ACH471-103

Key Exclusion Criteria:

1. History of a major organ transplant or hematopoietic stem cell/marrow transplant .

2. Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents for less than 24 weeks.

3. Known underlying bleeding disorders or any other conditions leading to anemia not primarily associated with PNH.

4. Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared and/or are on dialysis.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

Drug:
• ALXN2050
Oral FD inhibitor

Locations

Country	Name	City	State
Canada	Clinical Study Site	Sainte-Marie	Quebec
Canada	Clinical Study Site	Toronto	Ontario
Italy	Clinical Study Site	Avellino
Italy	Clinical Study Site	Florence
Korea, Republic of	Clinical Study Site	Seoul
New Zealand	Clinical Study Site	Auckland
New Zealand	Clinical Study Site	Christchurch
Spain	Clinical Study Site	Albacete
Turkey	Clinical Study Site	Bornova	Izmir
Turkey	Clinical Study Site	Fatih	Istanbul
United Kingdom	Clinical Study Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

Countries where clinical trial is conducted

Canada,  Italy,  Korea, Republic of,  New Zealand,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change In HgB Relative To Baseline		Week 12
Secondary	Number Of Patients Who Have Transfusion Avoidance		Up to Week 12
Secondary	Number Of RBC Units Transfused and Transfusion Instances		Up to Week 12
Secondary	Change In LDH Relative To Baseline		Week 12
Secondary	Change From Baseline In Absolute Reticulocyte Count		Week 12
Secondary	Change From Baseline In Direct Bilirubin		Week 12
Secondary	Change From Baseline In Total Bilirubin		Week 12
Secondary	Change From Baseline In PNH RBC Clone Size		Week 12
Secondary	Change From Baseline In C3 Complement Protein Fragment Deposition On PNH RBCs		Week 12
Secondary	Incidence of TEAEs, SAEs, and Events Leading To Discontinuation Of Study Medication		Through Study Completion
Secondary	Change in HgB Relative To Baseline		Long-term Extension Period
Secondary	Change in LDH Relative To Baseline		Long-term Extension Period
Secondary	Change in FACIT Fatigue Scale (Version 4) Scores Relative To Baseline		Week 12, Week 160