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CompletedNCT04469465Updated May 4, 2025Results posted

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

A Phase 3 interventional study of Danicopan and Placebo in Paroxysmal Nocturnal Hemoglobinuria, sponsored by Alexion Pharmaceuticals, Inc.. Completed at 62 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-04.

Sponsored by Alexion Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
86
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Paroxysmal Nocturnal Hemoglobinuria

Keywords

  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
  • Extravascular Hemolysis (EVH)
  • Factor D inhibitor
  • Complement
  • Danicopan
  • C5 inhibitor
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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 of \<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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
86 participants (actual)

Study arms

  • 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 · Drug: C5 Inhibitor

  • 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 · Drug: C5 Inhibitor

Interventions

  • DrugDanicopan

    Oral tablet

    Also known as: ALXN2040

  • DrugPlacebo

    Oral tablet

  • DrugC5 Inhibitor

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

05

What researchers measure

Primary outcomes

  1. Change From Baseline in Hgb at Week 12

    Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.

    Time frame: Baseline, Week 12

Secondary outcomes

  1. Percentage of Participants With Hgb Increase of ≥2 Grams/Deciliter (g/dL) (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12

    The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.

    Time frame: Week 12

  2. Percentage of Participants With Transfusion Avoidance Through Week 12

    Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.

    Time frame: Week 12

  3. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12

    The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue and better health-related quality of life. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  4. Change From Baseline in Absolute Reticulocyte Count at Week 12

    LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  5. Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment

    Time frame: 24 weeks prior to initiation of treatment to 24 weeks post initiation of treatment

  6. Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment

    Time frame: 24 weeks prior to initiation of treatment to 24 weeks post initiation of treatment

  7. Percentage of Participants With Transfusion Avoidance Through Week 24

    Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 24. Participants who discontinued study treatment early before Week 24 were considered as not achieving transfusion avoidance.

    Time frame: 24 weeks

  8. Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment

    LS mean and SE were produced using analysis of covariance (ANCOVA).

    Time frame: 12 weeks prior to initiation of treatment to 12 weeks post initiation of treatment

  9. Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment

    LS mean and SE were produced using ANCOVA.

    Time frame: 12 weeks prior to initiation of treatment to post 12 weeks of treatment (24 weeks)

  10. Change From Baseline FACIT Fatigue Scores at Week 24

    The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue and better health-related quality of life. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 24

  11. Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan

    The criterion was defined as Hgb stabilization avoidance of a \>1 g/dL (\>10 g/L) decrease in Hgb level at Week 24 from Week 12. Participants with transfusions within 4 weeks prior to Week 24 were considered as not meeting Hgb stabilization regardless of the actual value observed at Week 24.

    Time frame: Week 12 to Week 24

  12. Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24

    The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 24 and remaining transfusion free during the 12-Week TP2. Participants who withdrew from the study early during the 12-Week TP2 or had missing Hgb value at Week 24 were considered as not achieving the criterion.

    Time frame: Week 24

  13. Change From Baseline in Total and Direct Bilirubin at Week 12

    Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  14. Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12

    The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  15. Change From Baseline in Complement Component 3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12

    Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  16. Change From Baseline in Lactate Dehydrogenase at Week 12

    Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.

    Time frame: Baseline, Week 12

  17. Percentage of Participants With Hgb Normalization at Week 12

    Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 g/L, for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.

    Time frame: Week 12

  18. Percentage of Participants With Hgb Normalization at Week 24

    Hgb normalization was defined as Hgb value above LLN reference range. For male, the LLN was 125 g/L, for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 24 were considered as not meeting Hgb normalization regardless of actual value observed at Week 24.

    Time frame: Week 24

06

Results

Posted Jul 24, 2023

Participant flow

Treatment Period 1 (TP1)
Participant flow — Treatment Period 1 (TP1)
MilestoneDanicopan-DanicopanPlacebo-Danicopan
Started5729
Received at least 1 dose of study drug5729
Interim efficacy analysis set4221
Completed5527
Not completed22
Withdrew: Adverse event21
Withdrew: Withdrawal by subject01
Treatment Period 2 (TP2)
Participant flow — Treatment Period 2 (TP2)
MilestoneDanicopan-DanicopanPlacebo-Danicopan
Started5527
Received at least 1 dose of study drug5527
Completed5426
Not completed11
Withdrew: Adverse event11
Long-Term Extension (LTE)
Participant flow — Long-Term Extension (LTE)
MilestoneDanicopan-DanicopanPlacebo-Danicopan
Started5426
Received at least 1 dose of study drug5426
Completed4624
Not completed82
Withdrew: Withdrawal by subject30
Withdrew: Physician decision30
Withdrew: Noncompliance with study intervention10
Withdrew: Death01
Withdrew: Adverse event11

Outcome measures

PrimaryChange From Baseline in Hgb at Week 12

Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · g/L
Change From Baseline in Hgb at Week 12
g/LDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis29.40 ± 2.1074.96 ± 3.128
Full Analysis28.08 ± 1.9574.62 ± 3.018
Statistical analysis
  • Danicopan (TP1) vs Placebo (TP1) · Re-randomization Test · p = 0.0007
  • Danicopan (TP1) vs Placebo (TP1) · Re-randomization Test · p = 0.0007
  • Danicopan (TP1) vs Placebo (TP1) · Mixed Models Analysis · p = <0.0001 · Ls mean difference: 24.44 · 95% CI 16.90 to 31.99
  • Danicopan (TP1) vs Placebo (TP1) · Mixed Models Analysis · p = <0.0001 · Difference: 23.46 · 95% CI 16.31 to 30.61
SecondaryPercentage of Participants With Hgb Increase of ≥2 Grams/Deciliter (g/dL) (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12

The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Hgb Increase of ≥2 Grams/Deciliter (g/dL) (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12
percentage of participantsDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis59.5 (43.28 to 74.37)0 (0.00 to 16.11)
Full Analysis54.4 (40.66 to 67.64)0 (0.00 to 11.94)
SecondaryPercentage of Participants With Transfusion Avoidance Through Week 12

Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Transfusion Avoidance Through Week 12
percentage of participantsDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis83.3 (68.64 to 93.03)38.1 (18.11 to 61.56)
Full Analysis78.9 (66.11 to 88.62)27.6 (12.73 to 47.24)
SecondaryChange From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12

The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue and better health-related quality of life. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · units on a scale
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12
units on a scaleDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis7.97 ± 1.1281.85 ± 1.581
Full Analysis8.13 ± 0.9192.35 ± 1.289
SecondaryChange From Baseline in Absolute Reticulocyte Count at Week 12

LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · 10^12 cells/L
Change From Baseline in Absolute Reticulocyte Count at Week 12
10^12 cells/LDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis-0.0838 ± 0.008930.0035 ± 0.01268
Full Analysis-0.0925 ± 0.00816-0.0008 ± 0.01184
SecondaryChange in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
Time frame:
24 weeks prior to initiation of treatment to 24 weeks post initiation of treatment
Reported as:
Mean · RBC units
Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
RBC unitsDanicopan-Danicopan (TP2)
Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment-2.7 ± 4.86
SecondaryChange in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
Time frame:
24 weeks prior to initiation of treatment to 24 weeks post initiation of treatment
Reported as:
Mean · transfusion instances
Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
transfusion instancesDanicopan-Danicopan (TP2)
Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment-1.5 ± 2.41
SecondaryPercentage of Participants With Transfusion Avoidance Through Week 24

Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 24. Participants who discontinued study treatment early before Week 24 were considered as not achieving transfusion avoidance.

Time frame:
24 weeks
Reported as:
Number · percentage of participants
Percentage of Participants With Transfusion Avoidance Through Week 24
percentage of participantsDanicopan-Danicopan (TP2)
Percentage of Participants With Transfusion Avoidance Through Week 2469.1 (55.19 to 80.86)
SecondaryChange in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment

LS mean and SE were produced using analysis of covariance (ANCOVA).

Time frame:
12 weeks prior to initiation of treatment to 12 weeks post initiation of treatment
Reported as:
Least squares mean · RBC units
Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment
RBC unitsDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis-1.48 ± 0.271-0.18 ± 0.383
Full Analysis-1.44 ± 0.212-0.14 ± 0.297
SecondaryChange in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment

LS mean and SE were produced using ANCOVA.

Time frame:
12 weeks prior to initiation of treatment to post 12 weeks of treatment (24 weeks)
Reported as:
Least squares mean · transfusion instances
Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment
transfusion instancesDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis-0.92 ± 0.174-0.21 ± 0.246
Full Analysis-0.91 ± 0.138-0.11 ± 0.193
SecondaryChange From Baseline FACIT Fatigue Scores at Week 24

The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue and better health-related quality of life. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 24
Reported as:
Least squares mean · units on a scale
Change From Baseline FACIT Fatigue Scores at Week 24
units on a scaleDanicopan-DanicopanPlacebo-Danicopan
Change From Baseline FACIT Fatigue Scores at Week 246.21 ± 1.0465.64 ± 1.921
SecondaryPercentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan

The criterion was defined as Hgb stabilization avoidance of a \>1 g/dL (\>10 g/L) decrease in Hgb level at Week 24 from Week 12. Participants with transfusions within 4 weeks prior to Week 24 were considered as not meeting Hgb stabilization regardless of the actual value observed at Week 24.

Time frame:
Week 12 to Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan
percentage of participantsDanicopan-Danicopan
Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan58.2 (44.11 to 71.35)
SecondaryPercentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24

The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 24 and remaining transfusion free during the 12-Week TP2. Participants who withdrew from the study early during the 12-Week TP2 or had missing Hgb value at Week 24 were considered as not achieving the criterion.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24
percentage of participantsDanicopan-Danicopan
Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 2441.8 (28.65 to 55.89)
SecondaryChange From Baseline in Total and Direct Bilirubin at Week 12

Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · micromoles/L
Change From Baseline in Total and Direct Bilirubin at Week 12
micromoles/LDanicopan (TP1)Placebo (TP1)
Total Bilirubin (Interim Efficacy Analysis)-9.77 ± 1.692-2.15 ± 2.377
Direct Bilirubin (Interim Efficacy Analysis)-2.88 ± 0.3570.30 ± 0.503
Total Bilirubin (Full Analysis)-11.55 ± 1.541-1.42 ± 2.172
Direct Bilirubin (Full Analysis)-2.85 ± 0.3170.17 ± 0.447
SecondaryChange From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12

The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · percentage of the total cell population
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12
percentage of the total cell populationDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis24.60 ± 4.180-3.04 ± 5.864
Full Analysis26.35 ± 2.369-0.18 ± 2.960
SecondaryChange From Baseline in Complement Component 3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12

Baseline was defined as the last non-missing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · percentage of the total cell population
Change From Baseline in Complement Component 3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12
percentage of the total cell populationDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis-15.06 ± 2.8240.89 ± 4.394
Full Analysis-19.00 ± 1.8140.68 ± 2.690
SecondaryChange From Baseline in Lactate Dehydrogenase at Week 12

Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · units/L
Change From Baseline in Lactate Dehydrogenase at Week 12
units/LDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis-23.49 ± 8.287-2.92 ± 11.914
Full Analysis-25.60 ± 7.932-16.92 ± 11.380
SecondaryPercentage of Participants With Hgb Normalization at Week 12

Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 g/L, for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Hgb Normalization at Week 12
percentage of participantsDanicopan (TP1)Placebo (TP1)
Interim Efficacy Analysis28.6 (15.72 to 44.58)0 (0.00 to 16.11)
Full Analysis26.3 (15.54 to 39.66)0 (0.00 to 11.94)
SecondaryPercentage of Participants With Hgb Normalization at Week 24

Hgb normalization was defined as Hgb value above LLN reference range. For male, the LLN was 125 g/L, for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 24 were considered as not meeting Hgb normalization regardless of actual value observed at Week 24.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Hgb Normalization at Week 24
percentage of participantsDanicopan-Danicopan
Percentage of Participants With Hgb Normalization at Week 2420.0 (10.43 to 32.97)

Adverse events

Collected over Baseline (Day 1) up to 30 days after last dose of study drug (approximately 2 years). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Danicopan (TP1)0/57 (0%)3/57 (5.3%)43/57 (75.4%)
Placebo (TP1)0/29 (0%)2/29 (6.9%)18/29 (62.1%)
Danicopan-Danicopan (TP2)0/55 (0%)3/55 (5.5%)40/55 (72.7%)
Placebo-Danicopan (TP2)0/27 (0%)6/27 (22.2%)18/27 (66.7%)
Danicopan-Danicopan (LTE)0/54 (0%)7/54 (13%)48/54 (88.9%)
Placebo-Danicopan (LTE)1/26 (3.8%)6/26 (23.1%)24/26 (92.3%)
Most frequent serious events
Showing 10 of 34
Most frequent serious events
EventDanicopan (TP1)Placebo (TP1)Danicopan-Danicopan (TP2)Placebo-Danicopan (TP2)Danicopan-Danicopan (LTE)Placebo-Danicopan (LTE)
COVID-19Infections and infestations1/570/290/550/271/542/26
HaemolysisBlood and lymphatic system disorders0/570/290/552/270/540/26
Haemorrhagic diathesisBlood and lymphatic system disorders0/570/290/550/270/541/26
Pericardial effusionCardiac disorders0/570/290/550/270/541/26
Abdominal pain upperGastrointestinal disorders0/570/290/550/270/541/26
DiarrhoeaGastrointestinal disorders0/570/290/550/270/541/26
CystitisInfections and infestations0/570/290/550/270/541/26
Neutropenic sepsisInfections and infestations0/570/290/550/270/541/26
PneumoniaInfections and infestations0/570/290/550/270/541/26
Body temperature increasedInvestigations0/570/290/550/270/541/26
Most frequent other events
Showing 10 of 38
Most frequent other events
EventDanicopan (TP1)Placebo (TP1)Danicopan-Danicopan (TP2)Placebo-Danicopan (TP2)Danicopan-Danicopan (LTE)Placebo-Danicopan (LTE)
COVID-19Infections and infestations1/570/291/552/2711/547/26
PyrexiaGeneral disorders3/570/297/550/2713/543/26
ConstipationGastrointestinal disorders2/571/291/551/270/544/26
AstheniaGeneral disorders0/574/292/552/274/544/26
HeadacheNervous system disorders6/572/296/551/278/541/26
NasopharyngitisInfections and infestations1/570/291/550/277/541/26
ThrombocytopeniaBlood and lymphatic system disorders0/571/291/551/272/543/26
InsomniaPsychiatric disorders1/573/291/550/271/543/26
NauseaGastrointestinal disorders5/573/291/553/273/541/26
DiarrhoeaGastrointestinal disorders4/573/296/552/271/542/26

Baseline characteristics

Full Analysis Set: all enrolled participants who were randomized to either the danicopan or placebo treatment group.

Age, Continuous
Age, Continuous(years)Danicopan-DanicopanPlacebo-DanicopanTotal
Mean52.8 ± 17.0052.9 ± 14.3452.8 ± 16.07
Sex: Female, Male
Sex: Female, Male(Participants)Danicopan-DanicopanPlacebo-DanicopanTotal
Female342054
Male23932
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Danicopan-DanicopanPlacebo-DanicopanTotal
Hispanic or Latino617
Not Hispanic or Latino462470
Unknown or Not Reported549
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Danicopan-DanicopanPlacebo-DanicopanTotal
American Indian or Alaska Native101
Asian221032
Native Hawaiian or Other Pacific Islander000
Black or African American202
White281442
More than one race000
Unknown or Not Reported459
Hemoglobin (Hgb)
Hemoglobin (Hgb)(g/L)Danicopan-DanicopanPlacebo-DanicopanTotal
Mean76.7 ± 9.4778.9 ± 10.1177.5 ± 9.69
07

Study locations

62 sites
  • Research Site
    Los Angeles, California 90089, United States
  • Research Site
    Weston, Florida 33331, United States
  • Research Site
    Chicago, Illinois 60612, United States
  • Research Site
    Kalamazoo, Michigan 49007, United States
  • Research Site
    New York, New York 10065, United States
  • Research Site
    Dallas, Texas 75390, United States
  • Research Site
    Milwaukee, Wisconsin 53212, United States
  • Research Site
    Belem, 66053-000, Brazil
  • Research Site
    Curitiba, 80810-050, Brazil
  • Research Site
    Goiania, 74605-020, Brazil
  • Research Site
    Porto Alegre, 90110-270, Brazil
  • Research Site
    Rio De De Janeiro, 20211030, Brazil
  • Research Site
    Toronto, Ontario M5G 2C4, Canada
  • Research Site
    Brno, 625 00, Czechia
  • Research Site
    Lille, 59037, France
  • Research Site
    Paris, 75010, France
  • Research Site
    Pessac, 33604, France
  • Research Site
    Pierre-Benite, 69495, France
  • Research Site
    Ulm, 89081, Germany
  • Research Site
    Athens, 11527, Greece
  • Research Site
    Thessaloniki, 57010, Greece
  • Research Site
    Haifa, 31048, Israel
  • Research Site
    Jerusalem, 91120, Israel
  • Research Site
    Avellino, 83100, Italy
  • Research Site
    Bassano del Grappa, 36061, Italy
  • Research Site
    Firenze, 50134, Italy
  • Research Site
    Milano, 20122, Italy
  • Research Site
    Reggio Calabria, 89131, Italy
  • Research Site
    Roma, 00161, Italy
  • Research Site
    Bunkyo-Ku, 113 8603, Japan
  • Research Site
    Fukuoka, 812-8582, Japan
  • Research Site
    Kashiwa-shi, 277-8567, Japan
  • Research Site
    Kyoto-shi, 605-0981, Japan
  • Research Site
    Nagakute-shi, 480-1195, Japan
  • Research Site
    Ogaki-shi, 503-8502, Japan
  • Research Site
    Osaka-shi, 530-8480, Japan
  • Research Site
    Osakasayama, 589-8511, Japan
  • Research Site
    Shibuya-ku, 150-8935, Japan
  • Research Site
    Tanabe-shi, 646-8588, Japan
  • Research Site
    Toyoake-shi, 470-1192, Japan
  • Research Site
    Tsukuba-shi, 305-8576, Japan
  • Research Site
    Daejeon, 35015, Korea, Republic of
  • Research Site
    Seoul, 03722, Korea, Republic of
  • Research Site
    Seoul, 06351, Korea, Republic of
  • Research Site
    Seoul, 06591, Korea, Republic of
  • Research Site
    Suwon, 16247, Korea, Republic of
  • Research Site
    Kota Kinabalu, 88586, Malaysia
  • Research Site
    Kuching, 93586, Malaysia
  • Research Site
    Miri, 98000, Malaysia
  • Research Site
    Maastricht, 6229 HX, Netherlands
  • Research Site
    Gdansk, 80-214, Poland
  • Research Site
    Barcelona, 08036, Spain
  • Research Site
    Barcelona, 08916, Spain
  • Research Site
    Las Palmas de Gran Canaria, 35020, Spain
  • Research Site
    Madrid, 28040, Spain
  • Research Site
    Majadahonda, 28222, Spain
  • Research Site
    Sevilla, 41013, Spain
  • Research Site
    Taipei, 100, Taiwan
  • Research Site
    Bangkok, 10330, Thailand
  • Research Site
    Airdrie, ML6 0JS, United Kingdom
  • Research Site
    Leeds, BD7 1DP, United Kingdom
  • Research Site
    London, SE5 9NU, United Kingdom
08

References and documents

Publications

  • Lee JW, Griffin M, Kim JS, Lee Lee LW, Piatek C, Nishimura JI, Carrillo Infante C, Jain D, Liu P, Filippov G, Sicre de Fontbrune F, Risitano A, Kulasekararaj AG; ALXN2040-PNH-301 Investigators. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. Lancet Haematol. 2023 Dec;10(12):e955-e965. doi: 10.1016/S2352-3026(23)00315-0. PubMed 38030318 ↗

Study documents

  • Study protocol · Aug 8, 2022
  • Statistical analysis plan · Aug 10, 2022

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04469465
Lead sponsor
Alexion Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Jul 14, 2020
Start date
Dec 16, 2020
Primary completion
Jun 29, 2022
Completion
Jan 16, 2024
Results posted
Jul 24, 2023
Last update
May 4, 2025

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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