A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471

Study Identifier:
ACH471-205
ClinicalTrials.gov Identifier:
NCT03459443
EudraCT Identifier:
2017-002674-39
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals, Inc.
Study Contact Information:
N/A
Other

Available Documents

ProtocolStatistical Analysis Plan

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Drug: Danicopan
Date
Jun 2018 - Mar 2021
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 12+ years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • At least 12 years of age
  • Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary C3G or IC-MPGN
  • If a pre-treatment biopsy is obtained, or if a historical biopsy is available for review, it must have no more than 50% global fibrosis and no more than 50% of glomeruli with cellular crescents
  • Clinical evidence of ongoing disease based on significant proteinuria (defined as ≥500 mg/day of protein in a 24-hour urine) attributable to C3G disease or IC-MPGN in the opinion of the principal investigator (PI), and present prior to study entry and confirmed during Screening
  • If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (for example, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers), or mycophenolate mofetil, must be on a stable dose for at least 2 weeks prior to screening
  • Female participants must use an acceptable method birth control to prevent pregnancy during the clinical study and for 30 days after the last dose of study medication
  • Male participants must use highly effective birth control with a female partner to prevent pregnancy during the clinical study and for 90 days after the last dose of study medication
  • Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines
  • Must have access to emergency medical care
  • Key Exclusion Criteria
  • Have a history of a major organ transplant (for example, heart, lung, kidney, or liver) or hematopoietic stem cell/marrow transplant
  • Have a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study (for example, a comorbidity that is likely to result in deterioration of the participant's condition, affect the participant's safety during the study, or confound the results of the study), in the opinion of the PI
  • Have an eGFR \<30 milliliter/minute/1.73 m\^2 at the time of screening or at any time over the preceding 4 weeks
  • Is a renal transplant recipient or receiving renal replacement therapy
  • Have other renal diseases that would interfere with the interpretation of the study
  • Have evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is secondary
  • Have been diagnosed with or show evidence of hepatobiliary cholestasis
  • Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration or participants with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration
  • Have a history of febrile illness, a body temperature \>38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to danicopan administration
  • Have evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
  • Have a history of meningococcal infection within the prior year
  • Have a history of hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, and carbapenems, which, in the opinion of the investigator and/or an appropriately qualified immunology or infectious disease expert, would make it difficult to properly provide either empiric antibiotic therapy or treat an active infection.
  • Have participated in a clinical study in which an investigational drug was given within 30 days, or within 5 half-lives of the investigational drug, whichever is longer, prior to the first dose of ACH-0144471
  • Have received eculizumab at any dose or interval within the past 50 days prior to the first dose of ACH-0144471
  • Have received tacrolimus or cyclosporine within 2 weeks of the first dose of ACH-0144471
  • Have a 12-lead electrocardiogram (ECG) with a QT interval Fridericia correction formula \>450 millisecond (msec) for males or \>470 msec for females, or have ECG findings which, in the opinion of the PI, could put the participant at undue risk
  • Have received any drug known to prolong the corrected QT interval within 2 weeks of the first dose of ACH-0144471 and which, in the opinion of the PI, could put the participant at undue risk
  • Have any of the following laboratory abnormalities at screening:
  • Alanine transaminase \> upper limit of normal (ULN)
  • Aspartate aminotransferase \> ULN
  • Absolute neutrophil counts \<1,000/microliter
  • Total bilirubin \>1.5\* ULN
  • Indirect bilirubin \> ULN
  • Any laboratory abnormality that, in the opinion of the PI, would make the participant inappropriate for the study
  • Unwilling or unable to comply with the study protocol for any reason
Sex
Female & Male
Age
12+ years

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Drug: Danicopan
Date
Jun 2018 - Mar 2021
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 12+ years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • At least 12 years of age
  • Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary C3G or IC-MPGN
  • If a pre-treatment biopsy is obtained, or if a historical biopsy is available for review, it must have no more than 50% global fibrosis and no more than 50% of glomeruli with cellular crescents
  • Clinical evidence of ongoing disease based on significant proteinuria (defined as ≥500 mg/day of protein in a 24-hour urine) attributable to C3G disease or IC-MPGN in the opinion of the principal investigator (PI), and present prior to study entry and confirmed during Screening
  • If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (for example, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers), or mycophenolate mofetil, must be on a stable dose for at least 2 weeks prior to screening
  • Female participants must use an acceptable method birth control to prevent pregnancy during the clinical study and for 30 days after the last dose of study medication
  • Male participants must use highly effective birth control with a female partner to prevent pregnancy during the clinical study and for 90 days after the last dose of study medication
  • Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines
  • Must have access to emergency medical care
  • Key Exclusion Criteria
  • Have a history of a major organ transplant (for example, heart, lung, kidney, or liver) or hematopoietic stem cell/marrow transplant
  • Have a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study (for example, a comorbidity that is likely to result in deterioration of the participant's condition, affect the participant's safety during the study, or confound the results of the study), in the opinion of the PI
  • Have an eGFR \<30 milliliter/minute/1.73 m\^2 at the time of screening or at any time over the preceding 4 weeks
  • Is a renal transplant recipient or receiving renal replacement therapy
  • Have other renal diseases that would interfere with the interpretation of the study
  • Have evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is secondary
  • Have been diagnosed with or show evidence of hepatobiliary cholestasis
  • Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration or participants with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration
  • Have a history of febrile illness, a body temperature \>38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to danicopan administration
  • Have evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
  • Have a history of meningococcal infection within the prior year
  • Have a history of hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, and carbapenems, which, in the opinion of the investigator and/or an appropriately qualified immunology or infectious disease expert, would make it difficult to properly provide either empiric antibiotic therapy or treat an active infection.
  • Have participated in a clinical study in which an investigational drug was given within 30 days, or within 5 half-lives of the investigational drug, whichever is longer, prior to the first dose of ACH-0144471
  • Have received eculizumab at any dose or interval within the past 50 days prior to the first dose of ACH-0144471
  • Have received tacrolimus or cyclosporine within 2 weeks of the first dose of ACH-0144471
  • Have a 12-lead electrocardiogram (ECG) with a QT interval Fridericia correction formula \>450 millisecond (msec) for males or \>470 msec for females, or have ECG findings which, in the opinion of the PI, could put the participant at undue risk
  • Have received any drug known to prolong the corrected QT interval within 2 weeks of the first dose of ACH-0144471 and which, in the opinion of the PI, could put the participant at undue risk
  • Have any of the following laboratory abnormalities at screening:
  • Alanine transaminase \> upper limit of normal (ULN)
  • Aspartate aminotransferase \> ULN
  • Absolute neutrophil counts \<1,000/microliter
  • Total bilirubin \>1.5\* ULN
  • Indirect bilirubin \> ULN
  • Any laboratory abnormality that, in the opinion of the PI, would make the participant inappropriate for the study
  • Unwilling or unable to comply with the study protocol for any reason

Protocol Summary

The primary purpose of this study was to evaluate the efficacy of 12 months of oral ACH-0144471 (also known as danicopan and ALXN2040) in participants with C3G or IC-MPGN based on histologic scoring and proteinuria.

Trial Locations

Location
Status
Location
Clinical Study Site
Birmingham, Alabama, United States, 35294
Status
N/A
Location
Clinical Study Site
Stanford, California, United States, 94305
Status
N/A
Location
Clinical Study Site
New Haven, Connecticut, United States, 06511
Status
N/A
Location
Clinical Study Site
Cincinnati, Ohio, United States, 45221
Status
N/A
Location
Clinical Study Site
Columbus, Ohio, United States, 43210
Status
N/A
Location
Clinical Study Site
Philadelphia, Pennsylvania, United States, 19104
Status
N/A
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