Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
 
ClinicalTrials.gov Identifier: NCT03053102
Recruitment Status : Completed
First Posted : February 14, 2017
Results First Posted : June 2, 2021
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
Achillion, a wholly owned subsidiary of Alexion
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE February 1, 2017
First Posted Date  ICMJE February 14, 2017
Results First Submitted Date  ICMJE May 7, 2021
Results First Posted Date  ICMJE June 2, 2021
Last Update Posted Date June 2, 2021
Actual Study Start Date  ICMJE March 31, 2017
Actual Primary Completion Date November 14, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
Change-from-baseline in serum lactate dehydrogenase (LDH) levels [ Time Frame: Day 28 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
  • 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.
  • 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.
  • 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.
  • 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.
  • PK: Maximum Plasma Concentration (Cmax) [ Time Frame: Days 6 and 20 ]
    Serial blood samples were collected predose and up to 12 hours postdose.
  • PK: Time To Maximum Concentration (Tmax) [ Time Frame: Days 6 and 20 ]
    Serial blood samples were collected predose and up to 12 hours postdose.
  • Complement Alternative Pathway (AP) Functional Activity [ Time Frame: Baseline and Day 28 ]
    Serum AP functional activity was measured by the Wieslab functional immunoassay method.
  • Complement Bb [ Time Frame: Baseline and Day 28 ]
    Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • Change-from-baseline in hemoglobin (Hgb) [ Time Frame: Day 28 ]
  • Serious Adverse Events (SAEs), Grade 3 and Grade 4 Adverse Events (AEs), and AEs leading to discontinuation [ Time Frame: Up to Day 28 ]
  • Grade 3 and Grade 4 laboratory abnormalities [ Time Frame: Up to Day 28 ]
  • Profile of Pharmacokinetics: Area under the curve (AUC) [ Time Frame: Up to Day 28 ]
  • Profile of Pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Up to Day 28 ]
  • Profile of Pharmacokinetics: Time to maximum concentration (Tmax) [ Time Frame: Up to Day 28 ]
  • Profile of Pharmacodynamics: Complement pathway biomarkers (AP-Wieslab, factor D, and Bb) [ Time Frame: Up to Day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official Title  ICMJE 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
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention  ICMJE 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
Study Arms  ICMJE 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).
Intervention: Drug: Danicopan
Publications * 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. 2020 Oct 29;Online ahead of print. doi: 10.3324/haematol.2020.261826.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2018)
10
Original Estimated Enrollment  ICMJE
 (submitted: February 10, 2017)
4
Actual Study Completion Date  ICMJE November 14, 2018
Actual Primary Completion Date November 14, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Korea, Republic of,   New Zealand,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03053102
Other Study ID Numbers  ICMJE ACH471-100
2016-002652-25 ( EudraCT Number )
U1111-1190-3490 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Achillion, a wholly owned subsidiary of Alexion
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP