VALIANT: Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

• Sponsor: Apellis Pharmaceuticals, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05067127
• Collaborator: (none)
• Enrollment: 90
• Locations: 28
• Arms: 2
• Anticipated Duration (Months): 32.6
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.

Condition or Disease	Intervention/Treatment	Phase
C3G; IC-MPGN; C3 Glomerulopathy; C3 Glomerulonephritis; Complement 3 Glomerulopathy; Complement 3 Glomerulopathy (C3G); Complement 3 Glomerulonephritis; Dense Deposit Disease; DDD; Membranoproliferative Glomerulonephritis; Membranoproliferative Glomerulonephritis (MPGN); Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)	Drug: Pegcetacoplan; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Nov 12, 2021
• Anticipated Primary Completion Date: Mar 1, 2024
• Anticipated Study Completion Date: Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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)	Drug: Pegcetacoplan; Complement (C3) Inhibitor
Placebo Comparator: Group 2: Placebo administration Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly	Other: Placebo; Sterile solution of equal volume to active arm

Outcome Measures

Primary Outcome Measures

1. The proportion of subjects with a reduction from baseline in urine protein-to-creatinine ratio (uPCR) of at least 50% at Week 26 [Baseline to week 26]

Secondary Outcome Measures

1. The proportion of subjects with eGFR values that are stable or improved [Baseline to week 26]

2. For subjects with evaluable renal biopsies, the change in the C3G histologic index activity score (adults only) [Baseline to week 26]

3. The proportion of subjects with evaluable renal biopsies showing decreases in C3c staining on renal biopsy (adults only) [Baseline to week 26]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.

• A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).

• Evidence of active renal disease, based on one or more of the following:

1. In adults or adolescents with a baseline renal biopsy, at least 2+ staining for C3c on the baseline renal biopsy collected during screening, per the central pathology laboratory.

2. In adolescents not providing a baseline renal biopsy, at least one of the following:

• Serum C5b-9 level above the upper limit of normal (ULN) 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 lab results or medical history.

• No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy, for adult subjects or adolescent subjects providing a baseline biopsy.

• At least 1 g/day of proteinuria on a screening 24-hour urine collection, and a uPCR of at least 1000 mg/g on at least 2 first-morning urine samples collected during screening.

• 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.

• Stable regimen for C3G/IC-MPGN treatment, as described below:

1. Stable and optimized angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) therapy for at least 12 weeks prior to randomization, in the opinion of the investigator.

2. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil (MMF) and/or other allowed immunosuppressants that the patient is receiving for treatment of C3G) for at least 8 weeks prior to the baseline renal biopsy, and at least 12 weeks prior to randomization.

• 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.

Exclusion Criteria:

• Previous exposure to pegcetacoplan.

• 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.

• 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.

• Weight more than 100 kg at screening.

• Hypersensitivity to pegcetacoplan or to any of the excipients.

• History of meningococcal disease.

• 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

• An absolute neutrophil count <1000 cells/mm3 at screening.

• 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.

• Female subjects 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.

• Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the investigator, may place the subject at unacceptable risk by study participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Academic Medical Research Institute	Los Angeles	California	United States	90022
3	UCI Center for Clinical Research	Orange	California	United States	92868
4	Emory University School of Medicine	Atlanta	Georgia	United States	30322
5	The University of Iowa	Iowa City	Iowa	United States	52242
6	Renal and Transplant Associates of New England, PC	Springfield	Massachusetts	United States	01107
7	Cohen Children Hospital	New Hyde Park	New York	United States	11040
8	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania	United States	18017
9	MedResearch Inc	El Paso	Texas	United States	79902
10	Monash University	Box Hill		Australia	VIC 3128
11	St. Vincents Melbourne	Fitzroy		Australia	VIC 3065
12	CHU Sart-Tilman	Liège		Belgium	B-4000
13	Hospital Edouard Herriot, Hospices Civils de Lyon	Lyon		France	69437
14	CHU Montpellier, Hopital Lapeyronie	Montpellier		France	34295
15	CHU de Saint Etienne, Hospital Nord	Saint-Priest-en-Jarez		France	42055
16	Rangueil Hospital-University Hospital Center (CHU) of Toulouse	Toulouse		France	31059
17	Istituto di Ricerche Farmacologiche Mario Negri IRCCS	Milano		Italy	20156
18	Radboud University Medical Center	Nijmegen		Netherlands	6500 HB
19	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi	Łódź		Poland	90-153
20	SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Łódź		Poland	92-213
21	Fundació Puigvert	Barcelona		Spain	08025
22	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
23	Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica	Barcelona		Spain	08035
24	Hospital Materno Infantil Sant Joan de Deu	Barcelona		Spain	08950
25	Hospital Universitario 12 de Octubre, Nephrology Department	Madrid		Spain	28041
26	University Hospital of Virgen del Rocio	Sevilla		Spain	41013
27	Hospital Universitario Dr Peset	Valencia		Spain	46017
28	CHUV Lausanne	Lausanne		Switzerland	CH-1011

Sponsors and Collaborators

• Apellis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Study Website

Publications

None provided.

• Responsible Party: Apellis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05067127
• Other Study ID Numbers: APL2-C3G-310
• First Posted: Oct 5, 2021
• Last Update Posted: Aug 8, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative

Study Results

No Results Posted as of Aug 8, 2022