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

August 17, 2023 updated by: Alexion

An Open-Label Phase 2 Proof-of-Concept Study in Patients With C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) Treated With ACH-0144471

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was an open-label study to evaluate the efficacy of treatment with danicopan in participants 12 years of age or older with biopsy-confirmed C3G or IC-MPGN who had not undergone renal transplantation. All participants were to receive active treatment with danicopan for approximately 40 months. The starting dosage was to be 100 mg TID, and after 2 weeks, the dosage was to be increased to 200 mg TID for participants with body weight ≥ 60 kg or 150 mg TID for participants with body weight < 60 kg. Planned enrollment was approximately 20 participants.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia
        • Clinical Study Site
    • Queensland
      • Brisbane, Queensland, Australia
        • Clinical Study Site
    • Victoria
      • Melbourne, Victoria, Australia
        • Clinical Study Site
  • Belgium
      • Antwerpen, Belgium
        • Clinical Study Site
  • Italy
      • Ranica, Italy
        • Clinical Study Site
  • Netherlands
      • Leiden, Netherlands
        • Clinical Study Site
      • Nijmegen, Netherlands
        • Clinical Study Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Clinical Study Site
    • California
      • Stanford, California, United States, 94305
        • Clinical Study Site
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Clinical Study Site
    • Ohio
      • Cincinnati, Ohio, United States, 45221
        • Clinical Study Site
      • Columbus, Ohio, United States, 43210
        • Clinical Study Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Clinical Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. At least 12 years of age
  2. Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary C3G or IC-MPGN
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines
  9. Must have access to emergency medical care

Key Exclusion Criteria

  1. Have a history of a major organ transplant (for example, heart, lung, kidney, or liver) or hematopoietic stem cell/marrow transplant
  2. 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
  3. Have an eGFR <30 milliliter/minute/1.73 m^2 at the time of screening or at any time over the preceding 4 weeks
  4. Is a renal transplant recipient or receiving renal replacement therapy
  5. Have other renal diseases that would interfere with the interpretation of the study
  6. Have evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is secondary
  7. Have been diagnosed with or show evidence of hepatobiliary cholestasis
  8. 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
  9. 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
  10. Have evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
  11. Have a history of meningococcal infection within the prior year
  12. 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.
  13. 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
  14. Have received eculizumab at any dose or interval within the past 50 days prior to the first dose of ACH-0144471
  15. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of ACH-0144471
  16. 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
  17. 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

  18. 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
  19. Unwilling or unable to comply with the study protocol for any reason

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Danicopan
Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Drug: Danicopan
Danicopan was to be administered as an oral tablet.
Other Names:
  • ALXN2040
  • ACH-4471
  • ACH4471
  • 4471

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline In Composite Biopsy Score At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
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 the initial 12 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Baseline, end of initial 12-Month Treatment Period
Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
Proteinuria reduction was defined as ≥30% decrease from baseline based on 24-hour urine protein (mg/day).
Baseline, end of initial 12-Month Treatment Period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
Proteinuria was assessed based on 24-hour urine collections at baseline and end of the initial 12-month Treatment Period.
Baseline, end of initial 12-Month Treatment Period
Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
Proteinuria was assessed based on 24-hour urine collections at baseline and end of initial 12-month Treatment Period.
Baseline, end of initial 12-Month Treatment Period
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period
Time Frame: End of initial 12-Month Treatment Period
Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the Initial 12-Month Treatment Period, with eGFR as the dependent variable and time as the independent variable.
End of initial 12-Month Treatment Period
Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
Baseline, end of initial 12-Month Treatment Period
Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period
Time Frame: Baseline, end of initial 12-Month Treatment Period
Significant improvement relative to baseline was defined as a ≥ 25% increase from baseline in eGFR.
Baseline, end of initial 12-Month Treatment Period
Change From Baseline in eGFR Over 12 Months of Treatment For Participants Meeting eGFR Inclusion Criteria
Time Frame: End of initial 12-Month Treatment Period
Participants were eligible for enrollment if inclusion criteria were met including having an eGFR >=30 milliliters (mL)/minute (min)/1.73 square meter (m^2) at the time of screening or at any time over the preceding 4 weeks. This Outcome Measure was registered in case there were participants who were enrolled and ended up not meeting the Eligibility Criteria and was intended to report data for change from baseline in eGFR for only the participants who met the eligibility criteria (that is, participants who did not meet the eligibility criteria would have been excluded from analysis for this Outcome Measure). Since all enrolled participants met the Eligibility Criteria, none of the participants were excluded from this analysis. Therefore, this data is the same data that is presented in Outcome Measure #6 "Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period". Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
End of initial 12-Month Treatment Period
Change From Baseline In Measured GFR At The End Of The Initial 12-Month Treatment Period
Time Frame: End of initial 12-Month Treatment Period
Data for this Outcome Measure was to be collected where available. None of the sites collected data for this Outcome Measure.
End of initial 12-Month Treatment Period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alexion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 20, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 29, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 26, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACH471-205
  • 2017-002674-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

IPD Sharing Supporting Information Type

  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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