IgA NephropathyPhase 2NCT03453619

Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies

A Phase 2 study testing APL-2 in people with IgA Nephropathy and Lupus Nephritis, run by Apellis Pharmaceuticals, Inc. at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a Phase II trial assessing the safety and preliminary efficacy of daily APL-2 subcutaneous infusion administered for 16 weeks with a 6 month safety follow up, in patients with glomerulopathies Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy
What is being tested?: APL-2
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 17 sitesUnited States
Study dates: 26 Feb 2018to 26 Aug 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide written informed consent, and able to understand and comply with all scheduled procedures and other requirements of the study by the opinion of Principal Investigator (PI)
Patients must have a diagnosis of IgAN, LN, Primary MN, or C3G confirmed by renal biopsy and required measurements performed prior to study participation
IgAN: Prior biopsy results for C3 and C4d staining should be made available
LN: Diagnostic biopsy showing proliferative focal, diffuse, or membranous lesions (Class III, IV or V, respectively) by renal biopsy. Subject should have either a biopsy in the last 6 months, or evidence of disease activity (nephritic changes on urinalysis or nephrotic changes)
Primary MN: PLA2R positive titer plus nephrotic range proteinuria (defined as uPCR >2350 mg/g)
C3G plus one of the following: Low serum C3 level or historical renal biopsy within the last 3 years

Show all 10Show fewer

Have proteinuria >750 mg/g (calculated by uPCR on 24 hour urine collection) collected during the first screening visit (Visit 3a).
eGFR≥30mL/min/1.73 m2 calculated by CKD-EPI creatinine equation at screening visit 3a and currently not on dialysis
Must have stable or worsening renal disease, on stable and optimized treatment, in the opinion of the PI, for at least 2 months prior to the first dose of APL-2 (Visit 4); treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives and/or anti-proteinurics.
Willing to receive vaccinations against Neisseria meningitidis at least 2 weeks prior to dosing on Day 1 with a booster on Day 56 (for both vaccinations) and Pneumococcal and Hib vaccines at least 2 weeks prior to dosing on Day 1.

Who cannot join

Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b
ALT or AST >3.0 x the upper limit of normal at screening Visits 3a and 3b
Previous treatment with APL-2
History of solid organ transplant
Diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or positive serology at screening Visits 3a and 3b (previous HBV or HCV diagnosis cleared by treatment is allowed)
Renal disease secondary to another condition (e.g. infection, malignancy, monoclonal gammopathy, or a medication)

Show all 9Show fewer

Presence or suspicion of active bacterial or viral infection or severe recurrent bacterial infections
Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
Unwillingness to receive or intolerant of SC infusions of study medication or known allergy to ingredients in APL-2.

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

Washington Nephrology Associates
Alexandria, Virginia, 22304
Emory University
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Davita Clinical Research
Chesapeake, Virginia, 23320
Horizon Research Group
Coral Gables, Florida, 33134
HealthONE Physician Care, Rocky Mountain Hospital for Children
Denver, Colorado, 80205
American Research LLC
Jeffersonville, Indiana, 47130
Clinical Research Consultants
Kansas City, Missouri, 64111
University Clinical Health
Memphis, Tennessee, 38103
Northwest Louisiana Nephrology LLC
Shreveport, Louisiana, 71101
Stanford University
Stanford, California, 94305
Washington Nephrology Associates
Takoma Park, Maryland, 20912
Davita Clinical Research
The Bronx, New York, 10461
Westchester Medical Center
Valhalla, New York, 10595
Washington Nephrology Associates
Washington D.C., District of Columbia, 20037
Milwaukee Nephrologists
Wauwatosa, Wisconsin, 53226
Southeastern Nephrology Associates
Wilmington, North Carolina, 28401

Other trials in United States

About this study

Official title: A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease)

Conditions: IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, C3 Glomerulonephritis, Dense Deposit Disease
Being tested: APL-2
Medical subject headings: Glomerulonephritis, IGA, Lupus Nephritis, Glomerulonephritis, Membranous, Glomerulonephritis, Membranoproliferative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

APL-2Drug
APL-2 administered as a daily subcutaneous infusion for 48 weeks

Study groups in NCT03453619
Study group	Role	What they receive
APL-2	Experimental	Open Label, Study Drug, APL-2 Receives: Drug: APL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Change From Baseline in Proteinuria at Week 48
Change from baseline in proteinuria was assessed based on urinary protein-to-creatinine ratio (uPCR). Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Measured: Baseline (Day 1) and Week 48
Part B: Change From Baseline in Proteinuria at Week 168
Change from baseline in proteinuria was assessed based on uPCR. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Baseline (Part A, Week 48) and Week 168

Secondary outcomes (6)

Parts A and B: Change From Baseline in Serum Complement 3 (C3) Levels at Week 48 of Part A and Week 168 of Part B
Blood samples were collected to measure serum C3 levels. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in Alternative Pathway Hemolytic Assay (AH50) Activity at Week 48 of Part A and Week 168 of Part B
Blood samples were collected to measure AH50 activity. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in C3a Concentrations at Week 48 of Part A and Week 168 of Part B
Blood samples were collected to measure C3a concentrations. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in Serum Albumin Levels at Week 48 of Part A and Week 168 of Part B
Blood samples were collected to measure serum albumin levels. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Number of Subjects With Complete Clinical Remission at Week 48 of Part A and Week 168 of Part B
The complete clinical remission was defined as normalization of proteinuria as defined by <200 mg/g uPCR.
Measured: Part A: Week 48; Part B: Week 168
Parts A and B: Number of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 48 of Part A and Week 168 of Part B
The eGFR stabilization or improvement was defined as an eGFR value that was no more than a 25% decrease relative to baseline. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Measured: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 201826 Aug 2023

First posted5 Mar 2018
Study start26 Feb 2018
Primary completion16 Apr 2020
Study completion26 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for IgA NephropathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03453619
Sponsor's protocol ID: APL2-201
Status last verified: Jul 2024
First submitted: 27 Feb 2018
Last updated: 13 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Budge KL, Verlato A, Bin S, Salem FE, Perin L, La Manna G, Zaza G, Fiaccadori E, Cantarelli C, Cravedi P. Decay-Accelerating Factor Restrains Complement Activation and Delays Progression of Murine cBSA-Induced Membranous Nephropathy. Kidney360. 2023 Jun 1;4(6):e769-e776. doi: 10.34067/KID.0000000000000122. Epub 2023 Apr 8.
PubMed 37036696

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
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MYTP01 for Immune-Mediated Diseases
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A Study to Evaluate the Effect of ARGX-121 on the Change in Proteinuria in Adult Participants With IgAN
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All IgA Nephropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease)
ClinicalTrials.gov ID: NCT03453619
Acronym / sponsor ID: APL2-201
Conditions: IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, C3 Glomerulonephritis, Dense Deposit Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Apellis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 26 Feb 2018 (actual)
Primary completion: 16 Apr 2020 (actual)
Study completion: 26 Aug 2023 (actual)
First posted: 5 Mar 2018 (actual)
Results: Posted 13 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
APL-2	Experimental	Drug: APL-2Open Label, Study Drug, APL-2

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide written informed consent, and able to understand and comply with all scheduled procedures and other requirements of the study by the opinion of Principal Investigator (PI)
Patients must have a diagnosis of IgAN, LN, Primary MN, or C3G confirmed by renal biopsy and required measurements performed prior to study participation
Have proteinuria >750 mg/g (calculated by uPCR on 24 hour urine collection) collected during the first screening visit (Visit 3a).
eGFR≥30mL/min/1.73 m2 calculated by CKD-EPI creatinine equation at screening visit 3a and currently not on dialysis
Must have stable or worsening renal disease, on stable and optimized treatment, in the opinion of the PI, for at least 2 months prior to the first dose of APL-2 (Visit 4); treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives and/or anti-proteinurics.

Key exclusion criteria (9 listed)

Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b
ALT or AST >3.0 x the upper limit of normal at screening Visits 3a and 3b
Previous treatment with APL-2
History of solid organ transplant
Diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or positive serology at screening Visits 3a and 3b (previous HBV or HCV diagnosis cleared by treatment is allowed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
APL-2APL-2 administered as a daily subcutaneous infusion for 48 weeks	Drug	APL-2

Primary outcome

Part A: Change From Baseline in Proteinuria at Week 48
Time frame: Baseline (Day 1) and Week 48
Change from baseline in proteinuria was assessed based on urinary protein-to-creatinine ratio (uPCR). Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Part B: Change From Baseline in Proteinuria at Week 168
Time frame: Baseline (Part A, Week 48) and Week 168
Change from baseline in proteinuria was assessed based on uPCR. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.

6 secondary outcomes

Parts A and B: Change From Baseline in Serum Complement 3 (C3) Levels at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in Alternative Pathway Hemolytic Assay (AH50) Activity at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in C3a Concentrations at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Change From Baseline in Serum Albumin Levels at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Parts A and B: Number of Subjects With Complete Clinical Remission at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Week 48; Part B: Week 168
Parts A and B: Number of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 48 of Part A and Week 168 of Part B
Time frame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168

Results and safety

Results posted to the registry on 13 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IgAN Subjects	6	4
LN Subjects	2	1
PMN Subjects	5	1
C3G Subjects	8	7

Primary outcome: Part A: Change From Baseline in Proteinuria at Week 48

Time frame: Baseline (Day 1) and Week 48. Mean (95% Confidence Interval). Unit: ratio

Measure	Part A: IgAN Subjects n = 5	Part A: LN Subjects n = 1	Part A: PMN Subjects n = 1	Part A: C3G Subjects n = 7
Value	-0.1364 (-1.0641 to 0.7913)	0.3560 (NA to NA)	0.3430 (NA to NA)	-2.0347 (-3.9033 to -0.1662)

Population analysed: The intent-to-treat (ITT) population included all subjects who received at least 1 dose of pegcetacoplan. Only subjects analyzed at baseline and Week 48 are reported.

Primary outcome: Part B: Change From Baseline in Proteinuria at Week 168

Time frame: Baseline (Part A, Week 48) and Week 168. Mean (95% Confidence Interval). Unit: ratio

Measure	Part B: IgAN Subjects n = 2	Part B: LN Subjects n = 0	Part B: C3G Subjects n = 4
Value	-0.3385 (-3.8264 to 3.1494)	–	0.9718 (-4.7933 to 6.7368)

Population analysed: The ITT population included all subjects who received at least 1 dose of pegcetacoplan. Only subjects analyzed at baseline and Week 168 are reported.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAE data is reported from first dose of study drug (Day 1) up to 56 days after the last dose of study drug, up to approximately 1745 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: IgAN Subjects	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part A: LN Subjects	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part A: PMN Subjects	4 of 5 (80%)	5 of 5 (100%)	0 of 5
Part A: C3G Subjects	0 of 8 (0%)	8 of 8 (100%)	0 of 8
Part B: IgAN Subjects	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Part B: LN Subjects	1 of 1 (100%)	1 of 1 (100%)	0 of 1
Part B: PMN Subjects	0 of 0	0 of 0	0
Part B: C3G Subjects	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37036696Budge KL, Verlato A, Bin S, Salem FE, Perin L, La Manna G, Zaza G, Fiaccadori E, Cantarelli C, Cravedi P. Decay-Accelerating Factor Restrains Complement Activation and Delays Progression of Murine cBSA-Induced Membranous Nephropathy. Kidney360. 2023 Jun 1;4(6):e769-e776. doi: 10.34067/KID.0000000000000122. Epub 2023 Apr 8.

Related trials for IgA Nephropathy

RecruitingPhase 2
A Study of JADE101 in Participants With Immunoglobulin A Nephropathy
IgA Nephropathy
Not yet recruitingPhase 3
A Phase 3 Blinded Study of JADE101 in Participants With Immunoglobulin A Nephropathy
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Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
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Not yet recruiting
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RecruitingPhase 2
A Study to Evaluate the Effect of ARGX-121 on the Change in Proteinuria in Adult Participants With IgAN
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing APL-2 in people with IgA Nephropathy and Lupus Nephritis, run by Apellis Pharmaceuticals, Inc. at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Change From Baseline in Proteinuria at Week 48 (time frame: Baseline (Day 1) and Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03453619, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.