biopsy-confirmed C3 Glomerulopathy (C3G) or idiopathic Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) and eGFR >30 mL/min/1.73 m^2 MedDRA version: 20.0 Level: PT Classification code 10077827 Term: C3 glomerulopathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Code: ACH-0144471
Pharmaceutical Form: Tablet
INN or Proposed INN: Not available
CAS Number: 1903768-17-1
Current Sponsor code: ACH-0144471
Other descriptive name: ACH-0144471
Concentration un
Sponsors
Achillion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have completed the C3G Proof of Mechanism (POM) study (ACH471-201) (participation in the long-term follow-up portion of XML File Identifier: W7IWDxWydTWyK8OigMJAEawtqww= Page 18/34 ACH471-201 is not required) or must meet the following criteria: a. Must have biopsy-confirmed primary C3G or IC-MPGN b. Must have 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 PI, and present prior to study entry and confirmed during Screening. c. 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 d. Must be 12 years or age or older and capable of swallowing tablets 2. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (e.g., ACE inhibitors or angiotensin receptor blockers [ARBs]), or mycophenolate mofetil (MMF), must be on a stable dose for at least 2 weeks prior to screening 3. Female participants of childbearing potential must agree to use an acceptable method of contraception (as defined in Section 5.5.5) from the date of signing the informed consent to the first day of dosing (Day 1), and must agree to use a highly effective form of contraception (as defined in Section 5.5.5) from the first day of dosing to 30 days after their last dose of study drug. Female participants of childbearing potential must also have a negative serum pregnancy test during Screening and negative urine pregnancy test on Day 1. Female participants of non-childbearing potential need not employ a method of contraception. 4. Non-sterile male participants must agree to use a highly effective form of contraception (as defined in Section 5.5.5) with their partner(s) of childbearing potential from the first day of dosing to 90 days after their last dose of study drug. Male participants who are surgically sterile need not employ additional contraception. Male participants must agree not to donate sperm while enrolled in this study and for up to 90 days after their last dose of study drug. 5. Adult participants must be capable of providing written informed consent, and adolescent participants must be capable of providing written assent. All participants must be willing and able to comply with the requirements and restrictions listed in the consent form and with all procedures in the protocol, including, the visit schedule, the treatment plan, the schedule for laboratory testing, and other study procedures 6. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines 7. Must have access to emergency medical care Are the trial subjects under 18? yes Number of subjects for this age range: 3 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Have a history of a major organ transplant (e.g., heart, lung, kidney, 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 which 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 estimated GFR 38°C, or other evidence of a clinically significant active infection, within 14 days prior to ACH-0144471 administration 10. Have evidence of human immunodeficiency virus (HIV), 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 ECG with a QTcF >450 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 QTc 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 (ALT) > upper limit of normal (ULN) • Aspartate aminotransferase (AST) > ULN • Absolute neutrophil counts (ANC) 1.5× ULN • Indirect bilirubin > ULN • Any laboratory abnormality that, in the opinion of the PI, would make the particpant inappropriate for the study 19. Are unwilling or unable to comply with the study protocol for any reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 12 months of oral ACH-0144471 in patients with C3G or IC-MPGN based on: • Histologic scoring and proteinuria;Secondary Objective: •To evaluate the clinical effect of 12 months of oral ACH-0144471 in participants with C3G or IC-MPGN based on significant improvement in slope of estimated glomerular filtration rate (eGFR) relative to baseline over time • To evaluate for improvement in eGFR following treatment with ACH- 0144471 • Where available evaluate the change in measured (m) eGFR relative to baseline at the end of 12 months of treatment with ACH-0144471 • To evaluate the safety and tolerability of ACH-0144471 in partiecipants with C3G or IC-MPGN by assessing serious adverse events (SAEs);Primary end point(s): Primary efficacy endpoints: • Change from baseline in biopsy, based on a score incorporating changes in both the activity index and C3 staining at the end of 12 months of treatment. • Number and percent of participants with reduction in proteinuria relative to baseline at the end of 12 months of treatment;Timepoint(s) of evaluation of this end point: Please be referred to section 3.2.1.2 of the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: • Number and proportion of participants with significant (=25%) increase in eGFR relative to baseline at the end of 12 months of treatment • Change and percent change from baseline in proteinuria and eGFR over 12 months of treatment period for all participantson 3.2.1.2 of the protocol • Change and percent change from baseline in eGFR over 12 months of treatment for participants meeting eGFR inclusion criterion at study entry • Descriptive analysis of slope of GFR over the treatment period of - 4471 therapy;Timepoint(s) of evaluation of this end point: Please be referred to section 3.2.1.2 of the protocol | — |
Countries
Australia, Belgium, Italy, Netherlands, United States
Contacts
Public ContactClinical Operations
Achillion Pharmaceuticals, Inc.
Outcome results
None listed