NOBLE: Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN

• Sponsor: Apellis Pharmaceuticals, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04572854
• Collaborator: (none)
• Enrollment: 12
• Locations: 22
• Arms: 2
• Anticipated Duration (Months): 32.2
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a Phase 2, multicenter, open-label, randomized, controlled study designed to evaluate the safety and efficacy of pegcetacoplan in patients who have post-transplant recurrence of C3G or IC-MPGN.

Condition or Disease	Intervention/Treatment	Phase
C3G; IC-MPGN; Renal Transplant; Complement 3 Glomerulopathy; Complement 3 Glomerulopathy (C3G); Dense Deposit Disease (DDD); Membranoproliferative Glomerulonephritis; Membranoproliferative Glomerulonephritis (MPGN); Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN); C3 Glomerulopathy; C3 Glomerulonephritis; Complement 3 Glomerulonephritis	Drug: Pegcetacoplan	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC-MPGN
• Actual Study Start Date: Feb 23, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Pegcetacoplan treatment of 1080 mg (sub-cutaneous infusion) twice weekly will be given throughout the entire study.	Drug: Pegcetacoplan; Complement (C3) Inhibitor
Other: Group 2 No intervention given during the randomized controlled portion of the study (through week 12). After week 12, subjects will receive pegcetacoplan treatment.	Drug: Pegcetacoplan; Complement (C3) Inhibitor

Outcome Measures

Primary Outcome Measures

1. The primary efficacy endpoint is the proportion of subjects with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. [12 weeks after randomization]

Secondary Outcome Measures

1. The proportion of subjects with reduction in C3c staining on renal biopsy [52 weeks after randomization]

2. The proportion of subjects with stabilization or improvement in estimated glomerular filtration rate (eGFR) [52 weeks after randomization]

3. The proportion of subjects with stabilization or improvement of serum creatinine concentration [52 weeks after randomization]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years of age at screening

• Must have clinical and pathologic evidence of recurrent C3G or IC-MPGN

• Stable (not improving) or worsening disease, in the opinion of the investigator, in the 2 months preceding the first dose of pegcetacoplan

• eGFR ≥15 mL/min/1.73 m2, calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation for adults

• No more than 50% glomerulosclerosis or interstitial fibrosis on the screening renal allograft biopsy

• Stable regimen for recurrent C3G/IC-MPGN for at least 4 weeks prior to the screening renal allograft biopsy and from the time of the screening renal allograft biopsy until randomization

• Have received required vaccinations against N. meningitidis, S. pneumoniae, and H. influenzae (type B) or agree to receive vaccinations, if applicable vaccination records are not available. Vaccination is mandatory unless documented evidence exists that subjects are non-responders to vaccination.

Exclusion Criteria:

• Absolute neutrophil count <1000 cells/mm3 during screening

• Previous treatment with pegcetacoplan

• Evidence of rejection on the screening renal allograft biopsy that requires treatment

• Diagnosis or history of HIV, hepatitis B, or hepatitis C infection or positive serology at screening indicative of infection with any of these viruses

• Weight more than 100 kg at screening

• Hypersensitivity to pegcetacoplan or any of the excipients

• History of meningococcal disease

• Malignancy, except for the following:

• Cured basal or squamous cell skin cancer

• Curatively treated in situ disease

• Malignancy free and off treatment for ≥5 years

• Significant renal disease in the renal allograft secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, rejection, or a medication) that would, in the opinion of the investigator, confound interpretation of the study results

• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or 5 half-lives from the last dose of the investigational agent (whichever is longer) prior to screening

• Known or suspected hereditary fructose intolerance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck School of Medicine, University of Southern California	Los Angeles	California	United States	900033
2	Children's Hospital Colorado	Aurora	Colorado	United States	80045
3	Washington University, St.Louis	Saint Louis	Missouri	United States	63110
4	NYU Langone Health Transplant Insitute	New York	New York	United States	10016
5	CUIMC	New York	New York	United States	10032
6	Hospital de Alta Complejidad en Red El Cruce Dr. Nestor Carlos Kirchner	Florencio Varela	Provincia De Buenos Aires	Argentina	B1888AAE
7	Hospital Universitario Fundacion Favaloro	Buenos Aires		Argentina	C1093AAS
8	Monash Medical Centre	Clayton		Australia	3168
9	Medical University of Vienna	Vienna		Austria	1090
10	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS	Brazil	90020-090
11	UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP	Botucatu	Sao Paulo	Brazil	18618-686
12	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte		Brazil	CEP 30150-221
13	Clinical Research Center, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo		Brazil	05403-000
14	Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology	Lille		France	59000
15	Hopital Edouard Herriot, Hospices Civils de Lyon	Lyon		France	69437
16	Center Hospitalier Universitaire de Montpellier	Montpellier		France	34295 CEDEX 5
17	Istituto di Ricerche Farmacologiche Mario Negri IRCCS	Ranica		Italy	24020
18	Radbound University Medical Center	Nijmegen		Netherlands	6500 HB
19	Hospital Universitario 12 de Octubre, Nephrology Department	Madrid		Spain	28041
20	CHUV	Lausanne		Switzerland	1005
21	Imperial College Healthcare NHS Trust	London		United Kingdom	W12 0HS
22	Freeman Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7DN

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: NCT04572854
• Other Study ID Numbers: APL2-C3G-204
• First Posted: Oct 1, 2020
• Last Update Posted: Apr 13, 2022
• Last Verified: Apr 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; Recurrence

Study Results

No Results Posted as of Apr 13, 2022