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

NCT03459443 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ACH471-2052017-002674-39
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 13

Brief 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.

Conditions

C3 Glomerulonephritis; C3 Glomerulopathy; Immune Complex Membranoproliferative Glomerulonephritis; IC-MPGN; Dense Deposit Disease

Keywords

factor D; fD; alternative pathway; complement mediated disease; C3GN; DDD; idiopathic MPGN; MPGN Type I; MPGN Type II; MPGN Type III; Primary MPGN; MCGN; Mesangiocapillary Glomerulonephritis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline In Composite Biopsy Score At 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

  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 Outcomes (7)

• Change From Baseline In Proteinuria At End Of 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

  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

  End of initial 12-Month Treatment Period

• Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period

  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

  Baseline, end of initial 12-Month Treatment Period

Study Arms (1)

Danicopan

EXPERIMENTAL

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

Interventions

Danicopan DRUG

Danicopan was to be administered as an oral tablet.

Also known as: ACH-4471, ACH4471, 4471, ALXN2040

Danicopan

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (13)

Clinical Study Site

Birmingham, Alabama, 35294, United States

Location

Clinical Study Site

Stanford, California, 94305, United States

Location

Clinical Study Site

New Haven, Connecticut, 06511, United States

Location

Clinical Study Site

Cincinnati, Ohio, 45221, United States

Location

Clinical Study Site

Columbus, Ohio, 43210, United States

Location

Clinical Study Site

Philadelphia, Pennsylvania, 19104, United States

Location

Clinical Study Site

Sydney, New South Wales, Australia

Location

Clinical Study Site

Brisbane, Queensland, Australia

Location

Clinical Study Site

Melbourne, Victoria, Australia

Location

Clinical Study Site

Antwerp, Belgium

Location

Clinical Study Site

Ranica, Italy

Location

Clinical Study Site

Leiden, Netherlands

Location

Clinical Study Site

Nijmegen, Netherlands

Location

Related Publications (1)

• Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podos SD, Langman CB, Lightstone L, Parikh SV, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries AP, Wetzels JFM, Remuzzi G. Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies. Am J Nephrol. 2022;53(10):687-700. doi: 10.1159/000527167. Epub 2022 Nov 24.

  PMID: 36423588 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Interventions

danicopan

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

1.855.752.2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 9, 2018
• Study Start: June 20, 2018
• Primary Completion: March 29, 2021
• Study Completion: March 29, 2021
• Last Updated: August 21, 2023
• Results First Posted: August 11, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR

Locations

NL (2); BE (1); AU (3); US (6); IT (1)