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A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)

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ClinicalTrials.gov Identifier: NCT03369236
Recruitment Status : Completed
First Posted : December 11, 2017
Results First Posted : November 4, 2021
Last Update Posted : November 4, 2021
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.

Condition or disease Intervention/treatment Phase
C3 Glomerulopathy C3 Glomerulonephritis Dense Deposit Disease Drug: Danicopan Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Investigator and participant blinded; Sponsor open. Participants were randomized 1:1 to receive either danicopan or placebo for a period of 6 months, followed by an open-label extension.
Primary Purpose: Treatment
Official Title: A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G), With an Open-label Extension
Actual Study Start Date : June 12, 2018
Actual Primary Completion Date : December 11, 2019
Actual Study Completion Date : December 18, 2020


Arm Intervention/treatment
Active Comparator: Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)

Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period.

All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.

Drug: Danicopan
Danicopan was administered as an oral tablet.
Other Names:
  • ACH-4471
  • ACH4471
  • 4471
  • ACH-0144471 (formerly)
  • ALXN2040

Placebo Comparator: Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)

Placebo was administered TID during the 6-month treatment period.

All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.

Drug: Danicopan
Danicopan was administered as an oral tablet.
Other Names:
  • ACH-4471
  • ACH4471
  • 4471
  • ACH-0144471 (formerly)
  • ALXN2040

Drug: Placebo
Matching placebo was administered as an oral tablet.




Primary Outcome Measures :
  1. Change From Baseline In Composite Biopsy Score At Week 28 [ Time Frame: Baseline, Week 28 ]
    The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.

  2. Participants With Reduction In Proteinuria At Week 28 [ Time Frame: Week 28 ]
    Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).


Secondary Outcome Measures :
  1. Change From Baseline In Proteinuria At Week 28 [ Time Frame: Baseline, Week 28 ]
    Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.

  2. Percent Change From Baseline In Proteinuria At Week 28 [ Time Frame: Baseline, Week 28 ]
    Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.

  3. Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months [ Time Frame: 6 months ]
    Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the 6-month blinded treatment period, with eGFR as the dependent variable and time as the independent variable.

  4. Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment [ Time Frame: 12 months ]
    Slope of eGFR was estimated using a simple linear regression for each participant, including all data values during the open-label extension period with eGFR as the dependent variable and time as the independent variable.

  5. Change From Baseline In eGFR At Week 28 [ Time Frame: Baseline, Week 28 ]
    Change from baseline in eGFR at Week 28 is presented.

  6. Participants With Significant Improvement In eGFR Relative To Baseline At Week 28 [ Time Frame: Baseline, Week 28 ]
    Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.

  7. Participants With Significant Improvement In eGFR Relative To Baseline At Week 52 [ Time Frame: Baseline, Week 52 ]
    Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Had biopsy-confirmed primary C3G
  • Had clinical evidence of ongoing disease based on significant proteinuria, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
  • Was willing to comply with vaccination requirements.

Key Exclusion Criteria:

  • Had a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
  • Had ever received danicopan
  • Had more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
  • Had an estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared at the time of screening or at any time over the preceding 4 weeks
  • Was a renal transplant recipient or receiving renal replacement therapy
  • Had a history of a major organ transplant or hematopoietic stem cell/marrow transplant
  • Had evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary
  • Had other renal diseases that would interfere with interpretation of the study
  • Had been diagnosed with or showed evidence of hepatobiliary cholestasis
  • Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
  • Had a history of febrile illness, a body temperature >38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
  • Had evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
  • Had laboratory abnormalities at screening that, in the opinion of the PI, would make the participant inappropriate for the study

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): NCT03369236


Locations
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United States, Colorado
Clinical Study Site
Aurora, Colorado, United States, 80045
United States, Georgia
Clinical Study Site
Lawrenceville, Georgia, United States, 30046
United States, Iowa
Clinical Study Site
Iowa City, Iowa, United States, 52242
United States, Maryland
Clinical Study Site
Baltimore, Maryland, United States, 21205
United States, New York
Clinical Study Site
New York, New York, United States, 10016
Clinical Study Site
New York, New York, United States, 10032
United Kingdom
Clinical Study Site
London, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] May 15, 2020
Statistical Analysis Plan  [PDF] October 30, 2020

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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03369236    
Other Study ID Numbers: ACH471-204
2017-000663-33 ( EudraCT Number )
First Posted: December 11, 2017    Key Record Dates
Results First Posted: November 4, 2021
Last Update Posted: November 4, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Alexion Pharmaceuticals:
factor D
fD
Alternative pathway
Complement mediated disease
Membranoproliferative Glomerulonephritis
Primary MPGN
MPGN
Mesangiocapillary Glomerulonephritis
Idiopathic MPGN
DDD
C3GN
Additional relevant MeSH terms:
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Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
Immune System Diseases