Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05067127




Registration number
NCT05067127
Ethics application status
Date submitted
23/09/2021
Date registered
5/10/2021
Date last updated
26/07/2024

Titles & IDs
Public title
Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
Scientific title
A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
Secondary ID [1] 0 0
APL2-C3G-310
Universal Trial Number (UTN)
Trial acronym
VALIANT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
C3G 0 0
IC-MPGN 0 0
C3 Glomerulopathy 0 0
C3 Glomerulonephritis 0 0
Complement 3 Glomerulopathy 0 0
Complement 3 Glomerulopathy (C3G) 0 0
Complement 3 Glomerulonephritis 0 0
Dense Deposit Disease 0 0
DDD 0 0
Membranoproliferative Glomerulonephritis 0 0
Membranoproliferative Glomerulonephritis (MPGN) 0 0
Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pegcetacoplan
Other interventions - Placebo

Experimental: Group 1: Pegcetacoplan administration - Subcutaneous infusion of 20mL (1080 mg), twice weekly (for adults or adolescents \>50kg), and the three other weight-based doses either of 10mL (540mg), 12mL (648mg), or 15mL (810mg)

Placebo comparator: Group 2: Placebo administration - Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly


Treatment: Drugs: Pegcetacoplan
Complement (C3) Inhibitor

Other interventions: Placebo
Sterile solution of equal volume to active arm
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The log-transformed ratio of uPCR at week 26 compared to baseline
Timepoint [1] 0 0
Baseline to week 26
Secondary outcome [1] 0 0
The proportion of participants who meet the criteria for achieving a composite renal endpoint (a stable or improved eGFR compared to the baseline visit (=15% reduction in eGFR), and a =50% reduction in uPCR compared to the baseline visit.)
Timepoint [1] 0 0
Baseline to week 26
Secondary outcome [2] 0 0
The proportion of participants with a reduction of at least 50% from baseline in uPCR
Timepoint [2] 0 0
Baseline to week 26
Secondary outcome [3] 0 0
For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score
Timepoint [3] 0 0
Baseline to week 26
Secondary outcome [4] 0 0
The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline
Timepoint [4] 0 0
Baseline to week 26
Secondary outcome [5] 0 0
Change from baseline in eGFR
Timepoint [5] 0 0
Baseline to week 26

Eligibility
Key inclusion 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:

1. 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.
2. 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 (RBCs) per high-power field (HPF) and/or red blood cell casts on 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.
6. eGFR =30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.
7. Stable regimen for C3G/IC-MPGN treatment, as described below:

1. Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization
2. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 812 weeks prior to the baseline renal biopsy and randomization.
3. If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.
8. Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous exposure to pegcetacoplan.
2. 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.
3. Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.
4. Body weight greater than 100 kg at screening.
5. Hypersensitivity to pegcetacoplan or to any of the excipients.
6. History of meningococcal disease.
7. Malignancy, except for the following:

1. Cured basal or squamous cell skin cancer
2. Curatively treated in situ disease
3. Malignancy-free and off treatment for =5 years
8. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
9. An absolute neutrophil count <1000 cells/mm3 at screening.
10. Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.
11. Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug.
12. Presence or suspicion of severe infection during the screening period (including but not limited to recurrent or chronic infections) that, in the opinion of the investigator, may place the participant at unacceptable risk by study participation.
13. Known or suspected hereditary fructose intolerance.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD
Recruitment hospital [1] 0 0
Canberra Hospital - Renal Clinical Trials & Research Unit - Garran
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Monash University - Box Hill
Recruitment hospital [4] 0 0
St. Vincents Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
QLD 4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
VIC 3128 - Box Hill
Recruitment postcode(s) [4] 0 0
VIC 3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Massachusetts
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Michigan
Country [11] 0 0
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Missouri
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New Jersey
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New York
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Ohio
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Oregon
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Pennsylvania
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Texas
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Argentina
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Buenos Aires
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Argentina
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Córdoba
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Austria
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Innsbruck
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Edegem
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Belgium
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Leuven
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Belgium
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Liège
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Brazil
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Minas Gerais
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Brazil
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RS
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Brazil
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Botucatu
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Fortaleza
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Porto Alegre
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Brazil
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Recife
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Brazil
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Ribeirão Preto
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Brazil
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Rio De Janeiro
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Brazil
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São José Do Rio Preto
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Brazil
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São Paulo
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Prague
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France
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Bordeaux
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France
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Créteil
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Lyon
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Nantes
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Paris
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France
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Saint-Priest-en-Jarez
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France
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Strasbourg
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France
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Toulouse
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Germany
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Berlin
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Germany
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Essen
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Germany
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Hannover
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Mainz
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Germany
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Münster
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Regensburg
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Haifa
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Israel
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Petah Tikva
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Bari
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Bologna
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Messina
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Milano
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Padova
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Pavia
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Italy
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Rome
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Aichi
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Japan
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Gunma
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Japan
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Ishikawa
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Japan
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Nagasaki
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Shizuoka
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Osaka
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Tokyo
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Korea, Republic of
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Soeul
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Netherlands
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Nijmegen
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Poland
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Lódz
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Spain
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Barcelona
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Spain
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Madrid
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Santander
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Spain
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Sevilla
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Spain
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Valencia
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Switzerland
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Bern
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Switzerland
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Lausanne
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Switzerland
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Zürich
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United Kingdom
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Gloucester
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United Kingdom
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Leicester
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [90] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Apellis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05067127