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

November 20, 2023 updated by: Alexion Pharmaceuticals, Inc.

A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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. In the extension phase, participants received 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.

Study Type

Interventional

Enrollment (Actual)

12

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

  • Italy
      • Florence, Italy
        • Clinical Study Site
      • Naples, Italy
        • Clinical Study Site
  • United Kingdom
      • London, United Kingdom
        • Clinical Study Site
  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Clinical Study Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Clinical Study Site

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1: 100 mg Danicopan TID + Eculizumab
Starting dose of 100 mg danicopan TID in combination with eculizumab.
Drug: Danicopan
Participants received a daily oral dose of danicopan TID during the treatment period.
Drug: Eculizumab
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Other Names:
  • Soliris
Experimental: Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab
Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
Drug: Danicopan
Participants received a daily oral dose of danicopan TID during the treatment period.
Drug: Eculizumab
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Other Names:
  • Soliris
Experimental: Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab
Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.
Drug: Danicopan
Participants received a daily oral dose of danicopan TID during the treatment period.
Drug: Eculizumab
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Other Names:
  • Soliris
Experimental: Group 4: Optimal Dose of Danicopan TID + 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.
Drug: Danicopan
Participants received a daily oral dose of danicopan TID during the treatment period.
Drug: Eculizumab
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Other Names:
  • Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline In Hemoglobin At Week 24
Time Frame: Baseline, Week 24
Baseline, Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline In Lactate Dehydrogenase At Week 24
Time Frame: Baseline, Week 24
Baseline, Week 24
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
Time Frame: Within 24 weeks prior to first dose and during 24-week treatment period
Within 24 weeks prior to first dose and during 24-week treatment period
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment
Time Frame: Within 24 weeks prior to first dose and during 24-week treatment period
Within 24 weeks prior to first dose and during 24-week treatment period
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
Time Frame: Day 1 (after dosing) through end of study (maximum exposure: 1631 days)
An AE was defined 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.
Day 1 (after dosing) through end of study (maximum exposure: 1631 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals, Inc.

Collaborators

Achillion, a wholly owned subsidiary of Alexion

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.

General Publications

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)

May 8, 2018

Primary Completion (Actual)

September 20, 2019

Study Completion (Actual)

January 5, 2023

Study Registration Dates

First Submitted

March 15, 2018

First Submitted That Met QC Criteria

March 15, 2018

First Posted (Actual)

March 21, 2018

Study Record Updates

Last Update Posted (Estimated)

December 12, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACH471-101
  • 2016-003526-16 (EudraCT Number)
  • U1111-1209-4655 (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

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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