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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 : April 6, 2022
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 Long-Term Extension (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy. The Long-Term Extension period will consist of a first year of LTE(Year1) and a second year of optional LTE(Year2).All patients will complete 72 weeks of LTE(Year 1) assessments. After Week 72 (at the end of the first year of LTE), patients have the choice to complete participation in this study or continue to the optional second year (Year2) of LTE.

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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 31, 2022
Estimated Study Completion Date : December 31, 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: 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 patients with Hgb increase of ≥ 2 g/dL in the absence of transfusion [ Time Frame: Baseline, Week 12 ]
  2. Percentage Of Participants With Transfusion Avoidance [ Time Frame: Baseline through Week 12 ]
  3. Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores At Week 12 [ Time Frame: Baseline, Week 12 ]
    Scoring 0-52

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


Information from the National Library of Medicine

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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
  • Receiving an approved C5 inhibitor for at least 6 months prior to Day 1
  • Platelet count ≥30,000/microliters (µL)
  • Absolute neutrophil counts ≥500/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 (>3 x ULN in case of patients with documented liver iron overload defined by serum ferratin values

      • 500 ng/ML)
    • 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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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: April 6, 2022
Last Verified: March 2022

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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