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Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)

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ClinicalTrials.gov Identifier: NCT04469465
Recruitment Status : Recruiting
First Posted : July 14, 2020
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: Danicopan Drug: Placebo Drug: C5 Inhibitor Phase 3

Detailed Description:

This is a multiple-region, randomized, double-blind, placebo controlled, multiple-dose, study in participants with PNH who have clinically evident EVH on a C5 inhibitor (eculizumab or ravulizumab).

Participants will be randomized to receive danicopan or placebo, in a 2:1 ratio for 12 weeks (Treatment Period 1) in addition to their C5 inhibitor (eculizumab or ravulizumab) therapy. At Week 12, participants randomized to receive placebo will be switched to danicopan in addition to their C5 inhibitor for an additional 12 weeks (Treatment Period 2) and participants randomized to danicopan will continue on danicopan for an additional 12 weeks, while remaining on their ongoing C5 inhibitor therapy.

At the end of the 2 treatment periods (Week 24), participants may enter a 1-year Long-Term Extension (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)
Actual Study Start Date : December 16, 2020
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Danicopan + C5 Inhibitor
Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2).
Drug: Danicopan
Oral tablet
Other Name: ALXN2040

Drug: C5 Inhibitor
Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.

Placebo Comparator: Placebo + C5 Inhibitor
Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2).
Drug: Danicopan
Oral tablet
Other Name: ALXN2040

Drug: Placebo
Oral tablet

Drug: C5 Inhibitor
Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.




Primary Outcome Measures :
  1. Change From Baseline In Hemoglobin (Hgb) At Week 12 [ Time Frame: Baseline, Week 12 ]

Secondary Outcome Measures :
  1. Percentage Of Participants With Transfusion Avoidance [ Time Frame: Baseline through Week 12 ]
  2. Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores At Week 12 [ Time Frame: Baseline, Week 12 ]
    Scoring 0-52

  3. Change From Baseline In Absolute Reticulocyte Count At Week 12 [ Time Frame: Baseline, Week 12 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of PNH
  • Clinically Evident EVH defined by:

    • Anemia (Hgb ≤9.5 gram/deciliter) with absolute reticulocyte count ≥120 x 10^9/liter
    • At least 1 packed red blood cell or whole blood transfusion within 6 months prior to the start of the study
  • Receiving a C5 inhibitor for at least 6 months prior to Day 1
  • Platelet count ≥30,000/microliters (µL)
  • Absolute neutrophil counts ≥750/μL
  • Documentation of/or willingness to receive vaccinations for N. meningiditis and prophylactic antibiotics as required

Exclusion Criteria:

  • History of a major organ transplant or hematopoietic stem cell transplantation (HSCT)
  • Participants with known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants
  • Known or suspected complement deficiency
  • Laboratory abnormalities at screening, including:

    • Alanine aminotransferase >2 x ULN
    • Direct bilirubin >2 x ULN (unless due to EVH or documented Gilbert's Syndrome)
  • Current evidence of biliary cholestasis
  • Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter squared and/or are on dialysis
  • Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04469465


Contacts
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Contact: Alexion Pharmaceuticals Inc. 855-752-2356 clinicaltrials@alexion.com

Locations
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United States, California
Clinical Trial Site Recruiting
Los Angeles, California, United States, 90033
United States, Illinois
Clinical Trial Site Recruiting
Chicago, Illinois, United States, 60612
United States, Texas
Clinical Trial Site Recruiting
Dallas, Texas, United States, 75231
Brazil
Clinical Trial Site Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90110-270
France
Clinical Trial Site Recruiting
Saint-Quentin cedex, Aisne, France, 02321
Clinical Trial Site Recruiting
Nice, Alpes Maritimes, France, 06200
Clinical Trial Site Recruiting
Marseille Cedex 9, Bouches-du-Rhone, France, 13273
Clinical Trial Site Recruiting
Lille cedex, Nord, France, 59037
Clinical Trial Site Recruiting
Paris cedex 10, Paris, France, 75475
Clinical Trial Site Recruiting
Pierre-Bénite, Rhone, France, 69495
Clinical Trial Site Recruiting
Pessac, France, 33604
Italy
Clinical Trial Site Recruiting
Reggio Calabria, Calabria, Italy, 89214
Clinical Trial Site Recruiting
Avellino, Campagnia, Italy, 83100
Clinical Trial Site Recruiting
Milano, Lombardia, Italy, 20122
Clinical Trial Site Recruiting
Firenze, Toscana, Italy, 50134
Clinical Trial Site Recruiting
Bassano Del Grappa, Vicenza, Italy, 36061
Japan
Clinical Trial Site Recruiting
Fukushima-shi, Fukushima-ken, Japan, 960-1295
Clinical Trial Site Recruiting
Ogaki-shi, Gifu, Japan, 503-8502
Clinical Trial Site Recruiting
Tsukuba-shi, Ibaraki, Japan, 305-8576
Clinical Trial Site Recruiting
Suita-shi, Osaka, Japan, 565-0871
Clinical Trial Site Recruiting
Shinjuku-Ku, Tokyo, Japan, 160-0023
Clinical Trial Site Recruiting
Tanabe-shi, Wakayama, Japan, 646-8588
Korea, Republic of
Clinical Trial Site Recruiting
Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
Clinical Trial Site Recruiting
Daegu, Korea, Republic of, 42472
Clinical Trial Site Recruiting
Daejeon, Korea, Republic of, 35015
Clinical Trial Site Recruiting
Seoul, Korea, Republic of, 03080
Clinical Trial Site Recruiting
Seoul, Korea, Republic of, 03722
Clinical Trial Site Recruiting
Seoul, Korea, Republic of, 05505
Clinical Trial Site Recruiting
Seoul, Korea, Republic of, 06591
Spain
Clinical Trial Site Recruiting
Majadahonda, Madrid, Spain, 28222
Clinical Trial Site Recruiting
Málaga, Malaga, Spain, 29010
Clinical Trial Site Recruiting
Barcelona, Spain, 08035
Clinical Trial Site Recruiting
Barcelona, Spain, 08036
Clinical Trial Site Recruiting
Madrid, Spain, 28040
Clinical Trial Site Recruiting
Sevilla, Spain, 41013
Thailand
Clinical Trial Site Recruiting
Pathum Wan, Bangkok, Thailand, 10330
United Kingdom
Clinical Trial Site Recruiting
London, Greater London, United Kingdom, SE5 9NU
Clinical Trial Site Recruiting
Airdrie, North Lanarkshire, United Kingdom, ML6 0JS
Clinical Trial Site Recruiting
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Sponsors and Collaborators
Alexion Pharmaceuticals
Additional Information:
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04469465    
Other Study ID Numbers: ALXN2040-PNH-301
2019-003829-18 ( EudraCT Number )
First Posted: July 14, 2020    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexion Pharmaceuticals:
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Extravascular Hemolysis (EVH)
Factor D inhibitor
Complement
Danicopan
C5 inhibitor
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Hemolysis
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases
Pathologic Processes