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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03053102
Recruitment Status : Completed
First Posted : February 14, 2017
Results First Posted : June 2, 2021
Last Update Posted : June 2, 2021
Achillion, a wholly owned subsidiary of Alexion
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH) Drug: Danicopan Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 31, 2017
Actual Primary Completion Date : November 14, 2018
Actual Study Completion Date : November 14, 2018

Arm Intervention/treatment
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).
Drug: Danicopan
Danicopan was administered as multiple oral doses over a period of at least 28 days.
Other Names:
  • ACH-0144471
  • ACH-4471
  • ACH4471
  • 4471
  • ALXN2040

Primary Outcome Measures :
  1. Change From Baseline In Serum LDH Levels At Day 28 [ Time Frame: Baseline, Day 28 ]
    Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.

Secondary Outcome Measures :
  1. Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84 [ Time Frame: Baseline, Days 28 and 84 ]
    Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels.

  2. 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) ]
    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.

  3. 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). ]
    Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE.

  4. 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 ]
    Serial blood samples were collected predose and up to 8 hours postdose.

  5. PK: Maximum Plasma Concentration (Cmax) [ Time Frame: Days 6 and 20 ]
    Serial blood samples were collected predose and up to 12 hours postdose.

  6. PK: Time To Maximum Concentration (Tmax) [ Time Frame: Days 6 and 20 ]
    Serial blood samples were collected predose and up to 12 hours postdose.

  7. Complement Alternative Pathway (AP) Functional Activity [ Time Frame: Baseline and Day 28 ]
    Serum AP functional activity was measured by the Wieslab functional immunoassay method.

  8. Complement Bb [ Time Frame: Baseline and Day 28 ]
    Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03053102

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Clinical Trial Site
Florence, Italy
Clinical Trial Site
Naples, Italy
Korea, Republic of
Clinical Trial Site
Seoul, Korea, Republic of
New Zealand
Clinical Trial Site
Auckland, New Zealand
United Kingdom
Clinical Trial Site
London, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
Achillion, a wholly owned subsidiary of Alexion
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] March 13, 2018
Statistical Analysis Plan  [PDF] December 6, 2018

Publications of Results:
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Responsible Party: Alexion Pharmaceuticals Identifier: NCT03053102    
Other Study ID Numbers: ACH471-100
2016-002652-25 ( EudraCT Number )
U1111-1190-3490 ( Other Identifier: UTN )
First Posted: February 14, 2017    Key Record Dates
Results First Posted: June 2, 2021
Last Update Posted: June 2, 2021
Last Verified: May 2021

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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
Keywords provided by Alexion Pharmaceuticals:
Additional relevant MeSH terms:
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Hemoglobinuria, Paroxysmal
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases