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

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALXN2050
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH) focused on measuring paroxysmal nocturnal hemoglobinuria, PNH, extravascular hemolysis, EVH, factor D inhibitor, complement, C5 inhibitor, danicopan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-label ALXN2050 Monotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Change In HgB Relative To Baseline

Secondary Outcome Measures

Number Of Patients Who Have Transfusion Avoidance
Number Of RBC Units Transfused and Transfusion Instances
Change In LDH Relative To Baseline
Change From Baseline In Absolute Reticulocyte Count
Change From Baseline In Direct Bilirubin
Change From Baseline In Total Bilirubin
Change From Baseline In PNH RBC Clone Size
Change From Baseline In C3 Complement Protein Fragment Deposition On PNH RBCs
Incidence of TEAEs, SAEs, and Events Leading To Discontinuation Of Study Medication
Change in HgB Relative To Baseline
Change in LDH Relative To Baseline
Change in FACIT Fatigue Scale (Version 4) Scores Relative To Baseline

Full Information

First Posted
November 6, 2019
Last Updated
May 16, 2023
Sponsor
Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT04170023
Brief Title
Study of the Oral Factor D (FD) Inhibitor ALXN2050 in PNH Patients as Monotherapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 16, 2019 (Actual)
Primary Completion Date
April 27, 2023 (Actual)
Study Completion Date
October 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
paroxysmal nocturnal hemoglobinuria, PNH, extravascular hemolysis, EVH, factor D inhibitor, complement, C5 inhibitor, danicopan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label ALXN2050 Monotherapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
ALXN2050
Other Intervention Name(s)
ACH-0145228
Intervention Description
Oral FD inhibitor
Primary Outcome Measure Information:
Title
Change In HgB Relative To Baseline
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Number Of Patients Who Have Transfusion Avoidance
Time Frame
Up to Week 12
Title
Number Of RBC Units Transfused and Transfusion Instances
Time Frame
Up to Week 12
Title
Change In LDH Relative To Baseline
Time Frame
Week 12
Title
Change From Baseline In Absolute Reticulocyte Count
Time Frame
Week 12
Title
Change From Baseline In Direct Bilirubin
Time Frame
Week 12
Title
Change From Baseline In Total Bilirubin
Time Frame
Week 12
Title
Change From Baseline In PNH RBC Clone Size
Time Frame
Week 12
Title
Change From Baseline In C3 Complement Protein Fragment Deposition On PNH RBCs
Time Frame
Week 12
Title
Incidence of TEAEs, SAEs, and Events Leading To Discontinuation Of Study Medication
Time Frame
Through Study Completion
Title
Change in HgB Relative To Baseline
Time Frame
Long-term Extension Period
Title
Change in LDH Relative To Baseline
Time Frame
Long-term Extension Period
Title
Change in FACIT Fatigue Scale (Version 4) Scores Relative To Baseline
Time Frame
Week 12, Week 160

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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 Platelet count ≥30,000/µL Absolute neurophil count (ANC) ≥750/ µL Eligibility Criteria Specific for Group 3: 1. Patient received danicopan during Study ACH471-103 Key Exclusion Criteria: 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.
Facility Information:
Facility Name
Clinical Study Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Clinical Study Site
City
Sainte-Marie
State/Province
Quebec
Country
Canada
Facility Name
Clinical Study Site
City
Avellino
Country
Italy
Facility Name
Clinical Study Site
City
Florence
Country
Italy
Facility Name
Clinical Study Site
City
Seoul
Country
Korea, Republic of
Facility Name
Clinical Study Site
City
Auckland
Country
New Zealand
Facility Name
Clinical Study Site
City
Christchurch
Country
New Zealand
Facility Name
Clinical Study Site
City
Albacete
Country
Spain
Facility Name
Clinical Study Site
City
Fatih
State/Province
Istanbul
Country
Turkey
Facility Name
Clinical Study Site
City
Bornova
State/Province
Izmir
Country
Turkey
Facility Name
Clinical Study Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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