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Study of the Oral Factor D (FD) Inhibitor ALXN2050 (ACH-0145228) in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy

Phase 1
Conditions
Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 21.1Level: PTClassification code 10034042Term: Paroxysmal nocturnal haemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Registration Number
EUCTR2019-003830-17-ES
Lead Sponsor
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
Inclusion Criteria

All patients must meet all of the following conditions:
1. Diagnosis of PNH.
2. Male or female, = 18 years of age (or minimum adult age in accordance with local legal requirements).

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) without the need for platelet transfusions.
7. Absolute neutrophil count (ANC) =750/ µL.

Eligibility Criteria Specific for Group 2:
Patients on stable eculizumab switching to ALXN2050 (Group 2) must meet the following criteria:
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 without the need for platelet transfusions
5. Absolute neurophil count (ANC) =750/ µL

Eligibility Criteria Specific for Group 3:
1. Patient received danicopan during Study ACH-471-103.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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

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 such as (but not limited to) cyclosporine, tacrolimus, mycophenolate, or others for less than 24 weeks prior to enrollment.
3. Known underlying bleeding disorders (eg, coagulation factor deficiencies, idiopathic thrombocytopenic purpura, Von Willebrand disease) 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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the efficacy of ALXN2050 based on improvement in hemoglobin (Hgb);Secondary Objective: • To evaluate the efficacy of ALXN2050 based on reduction in transfusion requirements<br>• To evaluate the efficacy of ALXN2050 based on lactate dehydrogenase (LDH)<br>• To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH);Primary end point(s): 1. Change in Hgb relative to baseline;Timepoint(s) of evaluation of this end point: 1. Week 12
Secondary Outcome Measures
NameTimeMethod
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