A study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in Patients with C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis (VALE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apellis Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

18 May 2023 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Apellis Pharmaceuticals, Inc

External identifiers

EU CT number

2023-504625-39-00

EudraCT number

2022-002833-33

WHO UTN

U1111-1290-7826

ClinicalTrials.gov

NCT05809531

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of this study is to establish the long-term safety and efficacy of pegcetacoplan in participants with C3G or IC-MPGN.

Secondary objectives 1

1. An additional exploratory objective is to characterize the long-term effects of treatment with pegcetacoplan in participants with C3G or ICMPGN, including PK, pharmacodynamics (PD), and immunogenic response.

Conditions and MedDRA coding

C3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002600-PIP03-21

Plan to share IPD

Yes

IPD plan description

Requests for access to the deidentified data will be reviewed by Apellis External Research Committee.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Completed participation in Study APL2-C3G-310 through the Week 52 visit requirements.
2. Experienced clinical benefit from pegcetacoplan while participating in the previous trial, in the opinion of the investigator.
3. Must remain on a stable regimen for C3G or IC-MPGN treatment according to the requirements of Study APL2–C3G–310.
4. Received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) according to the requirements of Study APL2-C3G-310 and agree to receive any additional vaccinations recommended according to Advisory Committee on Immunization Practices recommendations for adults or children with complement deficiencies and/or immunocompromising conditions or other similar local applicable guidelines.
5. Female participants of childbearing potential, defined as any woman who has experienced menarche and who is not permanently sterile or postmenopausal, must have a negative urine pregnancy test at visit 1 and must agree to use protocol-defined methods of contraception for the duration of the study through at least 90 days after receiving the last dose of pegcetacoplan.
6. Male participants must agree to use protocol-defined methods of contraception and agree to refrain from donating semen for the duration of the study through at least 90 days after receiving the last dose of pegcetacoplan.
7. Participants above the legal age of consent, in accordance with local regulations, must be willing and able to provide informed consent. The legally authorized representative of participants under the legal age of consent must be willing and able to provide informed consent; where appropriate, participants under the legal age of consent must also give their assent to participation in the study.
8. Willing and able to self-administer pegcetacoplan or have an identified caregiver who can perform the administration.

Exclusion criteria 4

1. Female participants who are or are planning to become 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.
2. Inability or unwillingness to cooperate with the requirements of the protocol.
3. Any condition that, in the opinion of the investigator, creates an undue risk for the participant by participating in the study or is likely to confound interpretation of the study results.
4. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The log-transformed ratio of urine protein-to-creatinine ratio (uPCR) over time compared to pretreatment baseline.

Secondary endpoints 7

1. The proportion of participants with estimated glomerular filtration rate (eGFR) values that are stable or improved from pretreatment values over time.
2. The proportion of participants achieving proteinuria <1 g/day over time.
3. Change from pretreatment in the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) Scale score.
4. Change from pretreatment in eGFR values over time.
5. For participants with pretreatment serum albumin levels below the lower limit of normal (LLN), the proportion of participants with normalization of serum albumin levels over time
6. For participants with pretreatment serum C3 levels below the LLN, the proportion of participant s with normalization of serum C3 levels over time.
7. The proportion of participants with progression to a clinical composite outcome (at least one of the following: doubling of serum creatinine, progression to chronic kidney disease stage 5 or ESRD, renal transplantation, or death) over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Apellis Pharmaceuticals Inc.

Sponsor organisation

Apellis Pharmaceuticals Inc.

Address

100 5th Avenue

City

Waltham

Postcode

02451-8703

Country

United States

Scientific contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trial

Public contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trial

Third parties 14

Locations

8 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 160 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications