APL2-C3G-310

JRCT ID: jRCT2041230022

Registered date:22/05/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: C3 GLOMERULOPATHY OR IMMUNE-COMPLEX MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
• Date of first enrollment: 18/08/2023
• Target sample size: 5
• Countries of recruitment: US,Japan,Canada,Japan,UK,Japan,France,Japan,Germany,Japan,Italy,Japan,Spain,Japan,Netherland,Japan,Belgium,Japan,Austria,Japan,Czech Republic,Japan,Poland,Japan,Switzeland,Japan,Israel,Japan,Austrarlia,Japan,Korea,Japan,Argentina,Japan,Brazil,Japan
• Study type: Interventional
• Intervention(s): All participants will receive SC infusions of pegcetacoplan or matching volumes of placebo twice weekly. All adult participants (regardless of weight), and adolescent participants who weigh at least 50 kg, will receive 20 mL SC infusions. Adolescent participants who weigh at least 35 kg but less than 50 kg will receive a reduced infusion volume (12 mL for the first infusion and 15 mL for each infusion thereafter). Adolescent participants who weigh at least 30 kg but less than 35 kg will receive a further reduced infusion volume (10 mL for the first 2 infusions and 12 mL twice weekly thereafter). Participant weight will be assessed at each visit; if an adolescent participants weight has changed, the dose and infusion volume should be adjusted accordingly.

Outcome(s)

• Primary Outcome: The log-transformed ratio of uPCR at week 26 compared to baseline

Secondary Outcome

The proportion of participants who meet the criteria for achieving a composite renal endpoint (a stable or improved eGFR compared to the baseline visit (less than 15% reduction in eGFR), and a more than 50% reduction in uPCR compared to the baseline visit.)
The proportion of participants with a reduction of at least 50% from baseline in uPCR
Change from baseline in eGFR
For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score
The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
2.A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).
3.Evidence of active renal disease, based on one or more of the following:
a.In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2 C3c staining on the baseline renal biopsy.
b.In adolescents not providing a baseline renal biopsy, at least one of the following:
Plasma sC5b-9 level above the upper limit of normal during screening
Serum C3 below the LLN during screening
Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells per high-power field and/or red blood cell casts on routine local or central microscopic analysis of urine
Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history
4.No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
5.At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.

Exclude criteria

1.Previous exposure to pegcetacoplan.
2.Evidence of improving renal disease in the 8 weeks prior to screening or during the screening period according to available data; improving renal disease is defined as more than 30% increase in eGFR or more than 50% decrease in proteinuria.
3.From a renal transplant participant, evidence of rejection that requires treatment in the baseline renal biopsy collected during screening.
4.C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.
5.Current or prior diagnosis of HIV, hepatitis B, or hepatitis C infection or positive serology during screening that is indicative of infection with any of these viruses.
6.Body weight greater than 100 kg at screening.
7.Hypersensitivity to pegcetacoplan or to any of the excipients.
8.History of meningococcal disease.
9.Malignancy, except for the following:
a.Cured basal or squamous cell skin cancer
b.Curatively treated in situ disease
c.Malignancy-free and off treatment for more than 5 years
10.Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
11.An absolute neutrophil count less than 1000 cells/mm3 at screening.

Related Information

• Primary Sponsor: Mizuno Masashi