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

NCT03472885 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACH471-1012016-003526-16U1111-1209-4655
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 5

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

PNH; Paroxysmal Nocturnal Hemoglobinuria; ACH-0144471; Danicopan; Eculizumab; ALXN2040

Outcome Measures

Primary Outcomes (1)

• Change From Baseline In Hemoglobin At Week 24

  Baseline, Week 24

Secondary Outcomes (4)

• Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment

  Within 24 weeks prior to first dose and during 24-week treatment period

• Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment

  Within 24 weeks prior to first dose and during 24-week treatment period

• Change From Baseline In Lactate Dehydrogenase At Week 24

  Baseline, 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

  Day 1 (after dosing) through end of study (maximum exposure: 1631 days)

Study Arms (4)

Group 1: 100 mg Danicopan TID + Eculizumab

EXPERIMENTAL

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

Drug: Danicopan; Drug: Eculizumab

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

EXPERIMENTAL

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

Drug: Danicopan; Drug: Eculizumab

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

EXPERIMENTAL

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

Drug: Danicopan; Drug: Eculizumab

Group 4: Optimal Dose of Danicopan TID + Eculizumab

EXPERIMENTAL

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; Drug: Eculizumab

Interventions

Danicopan DRUG

Participants received a daily oral dose of danicopan TID during the treatment period.

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

Eculizumab DRUG

Participants received intravenous eculizumab administered at the participant's usual dose and schedule.

Also known as: Soliris

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Achillion, a wholly owned subsidiary of Alexion: collaborator

Study Sites (5)

Clinical Study Site

Baltimore, Maryland, 21287, United States

Location

Clinical Study Site

Cleveland, Ohio, 44195, United States

Location

Clinical Study Site

Florence, Italy

Location

Clinical Study Site

Naples, Italy

Location

Clinical Study Site

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34314483 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

danicopan; eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Four groups will be studied and enrolled sequentially.

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 21, 2018
• Study Start: May 8, 2018
• Primary Completion: September 20, 2019
• Study Completion: January 5, 2023
• Last Updated: December 12, 2023
• Results First Posted: June 25, 2021

Record last verified: 2023-11

Locations

IT (2); US (2); GB (1)