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Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab (PNH)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Danicopan
Eculizumab
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH) focused on measuring PNH, Paroxysmal Nocturnal Hemoglobinuria, ACH-0144471, Danicopan, Eculizumab, ALXN2040

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Diagnosed with PNH
  • Have received at least one red blood cell transfusion within last 12 weeks
  • Anemia with adequate reticulocytosis
  • Must be on a stable regimen of eculizumab
  • Platelet count ≥ 40,000/microliter without the need for platelet transfusions
  • Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae or willingness to receive vaccinations based on local guidelines
  • Willingness to receive antibiotic prophylaxis
  • Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug
  • Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug

Key Exclusion Criteria:

  • Current evidence of bone marrow failure or aplastic anemia requiring treatment
  • History of a major organ transplant or hematopoietic stem cell/marrow transplant
  • Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
  • Documented C5 complement protein mutations
  • Known or suspected complement deficiency
  • Contraindication to any of the required vaccinations
  • Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection
  • History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
  • History of hypersensitivity reactions to commonly used antibacterial agents

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Sites / Locations

  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site
  • Clinical Study Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1: 100 mg Danicopan TID + Eculizumab

Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab

Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab

Group 4: Optimal Dose of Danicopan TID + Eculizumab

Arm Description

Starting dose of 100 mg danicopan TID in combination with eculizumab.

Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.

Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.

Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.

Outcomes

Primary Outcome Measures

Change From Baseline In Hemoglobin At Week 24

Secondary Outcome Measures

Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
Number Of Participants Without RBC Transfusions
Change From Baseline In Lactate Dehydrogenase At Week 24
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
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. Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Full Information

First Posted
March 15, 2018
Last Updated
February 1, 2023
Sponsor
Alexion
Collaborators
Achillion, a wholly owned subsidiary of Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT03472885
Brief Title
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab
Acronym
PNH
Official Title
A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
May 8, 2018 (Actual)
Primary Completion Date
September 20, 2019 (Actual)
Study Completion Date
January 5, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
Collaborators
Achillion, a wholly owned subsidiary of Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.
Detailed Description
The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH. The 24-week treatment period was followed by a long-term extension phase (ongoing). In the extension phase, participants receive the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase. Results are reported for the 24-week treatment period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, ACH-0144471, Danicopan, Eculizumab, ALXN2040

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Four groups will be studied and enrolled sequentially.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: 100 mg Danicopan TID + Eculizumab
Arm Type
Experimental
Arm Description
Starting dose of 100 mg danicopan TID in combination with eculizumab.
Arm Title
Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab
Arm Type
Experimental
Arm Description
Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
Arm Title
Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab
Arm Type
Experimental
Arm Description
Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.
Arm Title
Group 4: Optimal Dose of Danicopan TID + Eculizumab
Arm Type
Experimental
Arm Description
Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.
Intervention Type
Drug
Intervention Name(s)
Danicopan
Intervention Description
Participants received a daily oral dose of danicopan TID during the treatment period.
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention Description
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Primary Outcome Measure Information:
Title
Change From Baseline In Hemoglobin At Week 24
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
Time Frame
From 24 weeks prior to first dose through 24 weeks of treatment
Title
Number Of Participants Without RBC Transfusions
Time Frame
From 24 weeks prior to first dose through 24 weeks of treatment
Title
Change From Baseline In Lactate Dehydrogenase At Week 24
Time Frame
Baseline, Week 24
Title
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
Description
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. Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame
Day 1 (after dosing) through 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Diagnosed with PNH Have received at least one red blood cell transfusion within last 12 weeks Anemia with adequate reticulocytosis Must be on a stable regimen of eculizumab Platelet count ≥ 40,000/microliter without the need for platelet transfusions Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae or willingness to receive vaccinations based on local guidelines Willingness to receive antibiotic prophylaxis Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug Key Exclusion Criteria: Current evidence of bone marrow failure or aplastic anemia requiring treatment History of a major organ transplant or hematopoietic stem cell/marrow transplant Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater Documented C5 complement protein mutations Known or suspected complement deficiency Contraindication to any of the required vaccinations Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection History of hypersensitivity reactions to commonly used antibacterial agents Note: Additional inclusion/exclusion criteria may apply, per protocol.
Facility Information:
Facility Name
Clinical Study Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Clinical Study Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Clinical Study Site
City
Florence
Country
Italy
Facility Name
Clinical Study Site
City
Naples
Country
Italy
Facility Name
Clinical Study Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34314483
Citation
Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, Huang M, Geffner M, Brodsky RA. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021 Nov 18;138(20):1928-1938. doi: 10.1182/blood.2021011388.
Results Reference
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Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab

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