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

NCT03053102 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACH471-1002016-002652-25U1111-1190-3490
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 5

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

PNH; Paroxysmal; Hemoglobinuria

Outcome Measures

Primary Outcomes (1)

• Change From Baseline In Serum LDH Levels At Day 28

  Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.

  Baseline, Day 28

Secondary Outcomes (10)

• Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84

  Baseline, Days 28 and 84

• Change From Baseline In Serum LDH Levels At Day 84

  Baseline, Day 84

• Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size

  Baseline, Day 28, and Day 84

• Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation

  After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)

• Grade 3 And Grade 4 Laboratory Abnormalities

  After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).

Study Arms (1)

Danicopan

EXPERIMENTAL

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

Interventions

Danicopan DRUG

Danicopan was administered as multiple oral doses over a period of at least 28 days.

Also known as: ACH-0144471, ACH-4471, ACH4471, 4471, ALXN2040

Danicopan

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (5)

Clinical Trial Site

Florence, Italy

Location

Clinical Trial Site

Naples, Italy

Location

Clinical Trial Site

Auckland, New Zealand

Location

Clinical Trial Site

Seoul, South Korea

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (1)

• 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. 2021 Dec 1;106(12):3188-3197. doi: 10.3324/haematol.2020.261826.

  PMID: 33121236 RESULT

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemoglobinuria

Interventions

danicopan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 14, 2017
• Study Start: March 31, 2017
• Primary Completion: November 14, 2018
• Study Completion: November 14, 2018
• Last Updated: June 23, 2022
• Results First Posted: June 2, 2021

Record last verified: 2022-05

Locations

IT (2); GB (1); NZ (1); KR (1)