Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Treatments: Drug: Danicopan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03053102

2016-002652-25 (EudraCT Number)

U1111-1190-3490 (Other Identifier)

ACH471-100

Details and patient eligibility

About

The purpose of this study was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated participants with PNH.

Full description

After 12 weeks of treatment, participants deriving clinical benefit were offered enrollment in a separate long-term extension study (ACH471-103, NCT03181633).

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Currently untreated PNH participants with PNH Type III erythrocyte and/or granulocyte clone size ≥10% and anemia (hemoglobin <12 grams/deciliter) with adequate reticulocytosis (as determined by the Investigator).
• LDH ≥1.5 x the upper limit of normal.
• Platelets ≥50,000/microliter without the need for platelet transfusions.
• Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae, or willingness to receive vaccinations during the screening period.
• Negative pregnancy test for females prior to dosing and throughout the study.

Exclusion criteria

• History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
• Participants who had received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater.
• Participants who had received eculizumab at any dose or interval within the past 75 days before study entry.
• Participants with known or suspected complement deficiency.
• Participants with active bacterial infection or clinically significant active viral infection, a body temperature >38°Celsius, or other evidence of infection on Day 1, or with a history of febrile illness within 14 days prior to first study drug administration.
• History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection.
• Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Danicopan

Experimental group

Description:

Starting doses of danicopan ranged from 100 to 150 milligrams (mg) three times daily (TID), with subsequent dose escalation up to 200 mg TID based on response (clinical and biochemical) for 28 days (Part 1). Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2).

Treatment:

Drug: Danicopan