- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03053102
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
May 31, 2022 updated by: Alexion Pharmaceuticals
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
After 12 weeks of treatment, participants deriving clinical benefit were offered enrollment in a separate long-term extension study (ACH471-103, NCT03181633).
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florence, Italy
- Clinical Trial Site
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Naples, Italy
- Clinical Trial Site
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Seoul, Korea, Republic of
- Clinical Trial Site
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Auckland, New Zealand
- Clinical Trial Site
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London, United Kingdom
- Clinical Trial Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Danicopan
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).
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Danicopan was administered as multiple oral doses over a period of at least 28 days.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline In Serum LDH Levels At Day 28
Time Frame: Baseline, Day 28
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Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
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Baseline, Day 28
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Time Frame: Baseline, Days 28 and 84
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Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels.
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Baseline, Days 28 and 84
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Change From Baseline In Serum LDH Levels At Day 84
Time Frame: Baseline, Day 84
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Change from Baseline = Serum LDH levels on Day 84 - Baseline Serum LDH levels.
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Baseline, Day 84
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Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Time Frame: Baseline, Day 28, and Day 84
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PNH RBC, summed type III, clone size levels were assessed from Baseline to Day 28 and Day 84.
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population.
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Baseline, Day 28, and Day 84
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Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
Time Frame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
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An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction.
The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table.
A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
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After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
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Grade 3 And Grade 4 Laboratory Abnormalities
Time Frame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
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Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE.
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After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
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Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Time Frame: Days 6 and 20
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Serial blood samples were collected predose and up to 8 hours postdose.
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Days 6 and 20
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PK: Maximum Plasma Concentration (Cmax)
Time Frame: Days 6 and 20
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Serial blood samples were collected predose and up to 12 hours postdose.
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Days 6 and 20
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PK: Time To Maximum Concentration (Tmax)
Time Frame: Days 6 and 20
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Serial blood samples were collected predose and up to 12 hours postdose.
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Days 6 and 20
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Complement Alternative Pathway (AP) Functional Activity
Time Frame: Baseline and Day 28
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Serum AP functional activity was measured by the Wieslab functional immunoassay method.
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Baseline and Day 28
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Complement Bb
Time Frame: Baseline and Day 28
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Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
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Baseline and Day 28
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 31, 2017
Primary Completion (Actual)
November 14, 2018
Study Completion (Actual)
November 14, 2018
Study Registration Dates
First Submitted
February 1, 2017
First Submitted That Met QC Criteria
February 10, 2017
First Posted (Actual)
February 14, 2017
Study Record Updates
Last Update Posted (Actual)
June 23, 2022
Last Update Submitted That Met QC Criteria
May 31, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ACH471-100
- 2016-002652-25 (EudraCT Number)
- U1111-1190-3490 (Other Identifier: UTN)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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AlexionCompletedParoxysmal Nocturnal Hemoglobinuria (PNH)Belgium, France, Italy, Japan, Spain, Taiwan, United Kingdom, United States, Canada, Czechia, Germany, Sweden, Singapore, Korea, Republic of, Russian Federation, Austria, Poland, Argentina, Australia, Brazil, Estonia, Malaysia, Mexico, Thaila... and more
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Ra PharmaceuticalsCompletedParoxysmal Nocturnal Hemoglobinuria (PNH)United Kingdom, Australia, Canada, Denmark, Finland, Germany, Hungary, New Zealand
Clinical Trials on Danicopan
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Alexion PharmaceuticalsCompleted
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Alexion PharmaceuticalsCompleted
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Alexion Pharmaceuticals, Inc.CompletedParoxysmal Nocturnal HemoglobinuriaFrance, Italy, Spain, United States, Taiwan, Thailand, Korea, Republic of, Japan, Malaysia, Brazil, Germany, Israel, Czechia, Netherlands, Greece, United Kingdom, Canada, Poland
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Alexion PharmaceuticalsAchillion, a wholly owned subsidiary of AlexionCompleted