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

NCT03369236 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ACH471-2042017-000663-33
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 7

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.

Conditions

C3 Glomerulopathy; C3 Glomerulonephritis; Dense Deposit Disease

Keywords

factor D; fD; Alternative pathway; Complement mediated disease; Membranoproliferative Glomerulonephritis; Primary MPGN; MPGN; Mesangiocapillary Glomerulonephritis; Idiopathic MPGN; DDD; C3GN

Outcome Measures

Primary Outcomes (2)

• Change From Baseline In Composite Biopsy Score At 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.

  Baseline, Week 28

• Participants With Reduction In Proteinuria At Week 28

  Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).

  Week 28

Secondary Outcomes (7)

• Change From Baseline In Proteinuria At Week 28

  Baseline, Week 28

• Percent Change From Baseline In Proteinuria At Week 28

  Baseline, Week 28

• Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months

  6 months

• Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment

  12 months

• Change From Baseline In eGFR At Week 28

  Baseline, Week 28

Study Arms (2)

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

ACTIVE COMPARATOR

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

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

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Danicopan DRUG

Danicopan was administered as an oral tablet.

Also known as: ACH-4471, ACH4471, 4471, ACH-0144471 (formerly), ALXN2040

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

Placebo DRUG

Matching placebo was administered as an oral tablet.

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

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (7)

Clinical Study Site

Aurora, Colorado, 80045, United States

Location

Clinical Study Site

Lawrenceville, Georgia, 30046, United States

Location

Clinical Study Site

Iowa City, Iowa, 52242, United States

Location

Clinical Study Site

Baltimore, Maryland, 21205, United States

Location

Clinical Study Site

New York, New York, 10016, United States

Location

Clinical Study Site

New York, New York, 10032, United States

Location

Clinical Study Site

London, United Kingdom

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; rhoA GTP-Binding Protein

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

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2017
• First Posted: December 11, 2017
• Study Start: June 12, 2018
• Primary Completion: December 11, 2019
• Study Completion: December 18, 2020
• Last Updated: October 14, 2022
• Results First Posted: November 4, 2021

Record last verified: 2022-10

Locations

US (6); GB (1)