Proof of Concept Study of ACH-0145228 in Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Achillion Pharmaceuticals; Alexion Pharmaceuticals

Criteria

Key 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:

Eligibility Criteria Specific for Group 1:

This patient group must meet the following additional eligibility requirements:

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:

Patients in Group 3 need to fulfill the following criterion:

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 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.