Clinical trial NCT03053102: Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of ACH-0144471 in Untreated Patients With Paroxysmal Nocturnal Hemoglobinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: PNH
Paroxysmal
Hemoglobinuria
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Achillion, a wholly owned subsidiary of Alexion
First posted: 2017-02-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline In Serum LDH Levels At Day 28
timeFrame: Baseline, Day 28
Secondary outcomes:
measure: Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
timeFrame: Baseline, Days 28 and 84
measure: Change From Baseline In Serum LDH Levels At Day 84
timeFrame: Baseline, Day 84
measure: Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
timeFrame: Baseline, Day 28, and Day 84
measure: Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
timeFrame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
measure: Grade 3 And Grade 4 Laboratory Abnormalities
timeFrame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
measure: Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
timeFrame: Days 6 and 20
measure: PK: Maximum Plasma Concentration (Cmax)
timeFrame: Days 6 and 20
measure: PK: Time To Maximum Concentration (Tmax)
timeFrame: Days 6 and 20
measure: Complement Alternative Pathway (AP) Functional Activity
timeFrame: Baseline and Day 28
measure: Complement Bb
timeFrame: Baseline and Day 28
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Clinical Trial Site
city: Naples
country: Italy
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Auckland
country: New Zealand
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References:
citation: Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P. Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Dec 1;106(12):3188-3197. doi: 10.3324/haematol.2020.261826.