This study has been transitioned to CTIS with ID 2024-514130-20-00 check the CTIS register for the current data. The primary objective of this study is to assess the efficacy of twice-weekly SC doses of pegcetacoplan compared with that of placebo in…
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is the log-transformed ratio of urine
protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline.
Secondary outcome
The key secondary efficacy endpoints at week 26:
• 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.)
• The proportion of participants with reductions of at least 50% from baseline
in uPCR
• For participants with evaluable renal biopsies, the change from baseline in
the activity score of the C3G histological activity index score
• The proportion of participants with evaluable renal biopsies showing
decreases in C3c staining from baseline
Additional secondary efficacy endpoints (to be Evaluated at Week 26):
• Change from baseline in eGFR
• The proportion of participants achieving proteinuria <1 g/day
• For participants with serum albumin levels below the lower limit of normal
(LLN) at baseline, the proportion of participants with normalization of serum
albumin levels
• For participants with serum C3 levels below LLN at baseline, the proportion
of participants with normalization of serum C3 levels above the LLN
• The log-transformed ratio of uPCR at week 52 compared to baseline
• The change from baseline in the Kidney Disease Quality of Life (KDQOL) score
Background summary
C3G and IC-MPGN are rare, chronic diseases that are a result of uncontrolled or
improper activation of part of the immune system called the complement system.
In people with C3G or IC-MPGN, a protein called complement C3 is
over-activated, and can cause kidney damage when its breakdown products form
harmful deposits in the kidney. Over time, this stops the kidneys from
removing waste in the blood. This waste, if not removed from the blood, builds
up in the body and may lead to kidney failure. Symptoms associated with
damaged kidneys include blood and protein in urine, high blood pressure, and
water retention (swelling).
In this research study an investigational medication named pegcetacoplan
(peg-set-a-koé-plan) is being tested for the treatment of C3G or IC-MPGN.
Pegcetacoplan inhibits the C3 protein in the complement system, so this study
will help us find out if this action can slow or reduce kidney damage. Under
normal conditions, the complement system will help remove pathogens and damaged
cells without hurting the body. However, sometimes uncontrolled or improper
activation of the complement system can damage the body.
Study objective
This study has been transitioned to CTIS with ID 2024-514130-20-00 check the CTIS register for the current data.
The primary objective of this study is to assess the efficacy of twice-weekly
SC doses of pegcetacoplan compared with that of placebo in patients with
primary C3G or IC-MPGN on the basis of a reduction in proteinuria in the
setting of stable or improved eGFR.
Secondary Objectives
• To assess the effect of pegcetacoplan on estimated glomerular filtration
rate (eGFR)
• To assess the effect of pegcetacoplan on additional C3G/IC-MPGN disease-
related parameters
• To evaluate the safety of pegcetacoplan over 52 weeks of treatment
Study design
This is a Phase 3, randomized, placebo-controlled, double-blinded, multicenter
study to evaluate the safety and efficacy of twice-weekly SC infusions of
pegcetacoplan in patients diagnosed with primary C3G or IC-MPGN.
The planned duration of participation in the study for each participant is up
to approximately 70 weeks. The study will consist of 4 parts:
• Part 1: up to 10-week screening period
• Part 2: 26-week randomized controlled period (RCP)
• Part 3: 26-week open-label period
• Part 4: 8-week follow-up period (only for participants who do not roll into a
long-term extension study)
Intervention
All participants will receive SC infusions of pegcetacoplan or matching volumes
of placebo twice weekly. The planned dosing regimens for pegcetacoplan and the
matching volume of placebo. All adult participants (regardless of weight) and
adolescent participants who weigh at least 50 kg will receive 20-mL SC
infusions. Adolescent participants who weigh at least 35 kg but less than 50 kg
will receive a reduced infusion volume (12 mL for the first infusion and 15 mL
for each infusion thereafter). Adolescent participants who weigh at least 30 kg
but less than 35 kg will receive a further reduced infusion volume (10 mL for
the first 2 infusions and 12 mL twice weekly thereafter). Participant weight
will be assessed at each visit; if an adolescent subject*s weight has changed,
the dose and infusion volume should be adjusted accordingly.
Study burden and risks
Pegcetacoplan has the potential to address the underlying disease
pathophysiology of complement hyperactivity in C3G and IC-MPGN, and, therefore,
to provide benefit in these diseases with a high unmet medical need.
The safety of SC pegcetacoplan administration has been studied in multiple
Phase 2 and 3 studies for C3G, PNH, and autoimmune hemolytic anemia, with an
acceptable safety profile to date. Nonetheless, a number of safety monitoring
practices are being employed by this protocol to ensure participant safety,
including physical examination, vital signs monitoring, electrocardiograms
(ECGs), hematology (including coagulation), serum chemistry, urinalysis at
specified intervals, as well as prompt reporting of adverse events (AEs).
Infusion site/pump safety will be assessed during clinical visits, and any
significant finding from the assessment will be recorded as an AE. The volume
of blood planned for collection from each participant over the course of the
study will be minimized in order to limit the impact on the overall health of
these anemic participants.
Systemic complement inhibition might predispose individuals to infections
caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria
meningitidis, and Haemophilus influenzae. Vaccinations against these organisms
according to the most current Advisory Committee on Immunization Practices
(ACIP) recommendations for patients with complement deficiencies will be
required to minimize potential risk of infection. Vaccinations will be
initiated at least 2 weeks prior to receiving the first dose of pegcetacoplan;
therefore, prophylactic antibiotic use is not required. Body temperature and
vital signs will be monitored periodically, and relevant blood parameters
monitored regularly throughout the study to assess for signs of infection.
Participants will be counseled regarding this potential risk for infection and
given a patient safety wallet card in the event of an emergency. The
investigator should be contacted immediately in the event of a suspected
infection for guidance on appropriate action to be taken.
Apellis is not currently aware of any evidence associating pegcetacoplan use
with specific risks or complications of coronavirus disease 2019 (COVID-19).
Apellis recognizes the need to consider the public health risks of the COVID-19
pandemic within the context of conducting a clinical trial. Because these risks
may change as the pandemic evolves and may vary on the basis of geography
location, Apellis will continue to evaluate the risk/benefit around study
conduct on an ongoing and participant-by-participant basis.
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US
Listed location countries
Age
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:
a. 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.
b. 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 per high-power field and/or red blood
cell casts on routine 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:
a. 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
b. 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 12 weeks
prior to randomization.
c. 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) as per ACIP recommendations for adults
or children with complement deficiencies. Vaccination series should be
initiated at least 14 days prior to randomization. Vaccination is mandatory
unless documented evidence exists that participants are nonresponders to
vaccination.
9. Female participants of childbearing potential, defined as any women who have
experienced menarche and who are not permanently sterile or postmenopausal,
must have negative blood pregnancy tests at screening (and negative urine
pregnancy tests on Day 1) and must agree to use protocol-defined methods of
contraception from screening through at least 90 days after receiving the last
dose of pegcetacoplan.
10. Male participants must agree to use protocol-defined methods of
contraception and agree to refrain from donating semen from screening through
at least 90 days after receiving the last dose of pegcetacoplan.
11. 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.
12. Willing and able to self-administer pegcetacoplan or have an identified
caregiver who can perform the administration.
Exclusion criteria
1. Previous exposure to pegcetacoplan.
2. Evidence of improving renal disease in the 8 weeks prior to screening or
during the screening period according to available data; improving renal
disease is defined as >30% increase in eGFR or >50% decrease in proteinuria.
3. From a renal transplant subject, evidence of rejection that requires
treatment in the baseline renal biopsy collected during screening.
4. 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.
5. Current or prior diagnosis of HIV, hepatitis B, or hepatitis C infection or
positive serology during screening that is indicative of infection with any of
these viruses.
6. Weight more than 100 kg at screening.
7. Hypersensitivity to pegcetacoplan or to any of the excipients.
8. History of meningococcal disease.
9. Malignancy, except for the following:
a. Cured basal or squamous cell skin cancer
b. Curatively treated in situ disease
c. Malignancy-free and off treatment for >=5 years
10. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior
to the first dose of pegcetacoplan.
11. An absolute neutrophil count <1000 cells/mm3 at screening
12. Significant other renal disease that would, in the opinion of the
investigator, confound interpretation of study results.
13. 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 investigational agent (whichever is longer) prior to screening
period.
14. 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.
15. 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.
16. Inability to cooperate or 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.
17. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of
the investigator.
18. 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.
19. Known or suspected hereditary fructose intolerance.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-514130-20-00 |
| EudraCT | EUCTR2020-003767-25-NL |
| CCMO | NL77632.091.21 |