This study has been transitioned to CTIS with ID 2024-511544-36-00 check the CTIS register for the current data. Primary:To evaluate the efficacy of pegcetacoplan in improving the underlying pathophysiology of complement 3 glomerulopathy (C3G)/…
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint:
The primary efficacy endpoint is the proportion of subjects with reduction in
C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan.
Secondary outcome
Secondary Efficacy endpoints:
• The proportion of subjects with reduction in C3c staining on renal biopsy
after 52 weeks of treatment
• The proportion of subjects with stabilization or improvement in estimated
glomerular filtration rate (eGFR), over time
• The proportion of subjects with stabilization or improvement in serum
creatinine concentration, over time
• Changes from baseline biopsy in C3c staining over time
• Changes and percentage changes from baseline in eGFR and serum creatinine
concentration over time
Background summary
There are no therapies approved to prevent or reverse disease progression in
C3G or IC-MPGN.
Similar to other glomerular diseases, disease management includes nonspecific
measures to
manage proteinuria, hypertension, hyperlipidemia, edema, and other facets of
glomerular and chronic kidney disease. Despite these various measures, the
prognosis of C3G and IC-MPGN is poor as patients can progress to ESRD.
Renal transplantation is an option for patients who reach ESRD, but the
incidence of disease
recurrence is high, with up to 50% of patients losing their renal allografts
due to disease
recurrence. Therefore, a therapy that can protect the kidneys, native or
transplanted, from ongoing
damage due to complement hyperactivity would be highly desirable. An ongoing
study, APL2-201, is studying pegcetacoplan in patients with C3G who have not
undergone a renal transplant. Preliminary data from the APL2-201 study indicate
that pegcetacoplan is able to target the complement hyperactivity of C3G. The
sponsor now aims to study the safety and efficacy of pegcetacoplan in patients
with recurrence of C3G or IC-MPGN in a renal allograft.
This study will explore the safety and biologic activity of pegcetacoplan in
patients with C3G or
IC-MPGN recurrence post-transplantation. Renal biopsies will be obtained at
multiple time
points to assess the ability of pegcetacoplan to reduce the amount of C3c
glomerular deposition,
one of the histologic hallmarks of these diseases. This finding, along with
increases in intact
serum C3, would provide strong evidence that pegcetacoplan is addressing the
underlying
pathophysiology of the disease by preventing excessive production of C3
breakdown products,
and their subsequent deposition into the kidney.
Study objective
This study has been transitioned to CTIS with ID 2024-511544-36-00 check the CTIS register for the current data.
Primary:
To evaluate the efficacy of pegcetacoplan in improving the underlying
pathophysiology of complement 3 glomerulopathy (C3G)/immune complex
membranoproliferative glomerulonephritis (IC-MPGN) after 12 weeks of treatment.
Secondary:
• To evaluate the effect of pegcetacoplan on key clinical manifestations of the
disease after 52 weeks of treatment.
• To evaluate the safety of pegcetacoplan for up to 52 weeks in patients with
recurrent C3G/IC-MPGN in a renal allograft.
Study design
This Phase 2, multicenter, open-label, randomized, controlled study is designed
to evaluate the safety and efficacy of pegcetacoplan in patients who have post-
transplant recurrence of C3G or IC-MPGN. There will be up to 12 patients
enrolled in this study. There are 3 periods of this study:
Part A, Core Study:
• Screening period: up to an 8-week week screening period, during which a
screening renal allograft biopsy will occur
• Main period: a 52-week study period that contains 2 portions (Controlled and
Noncontrolled) during which patients will be randomized to either Group 1 or
Group 2 at the Week 1 study visit:
- Controlled portion: Weeks 1-12 of the study
- Group 1: Up to 9 patients will be randomized to this treatment group and
will receive pegcetacoplan treatment throughout the entire study; biopsies will
occur at Week 12.
- Group 2: Up to 3 patients will be randomized to this treatment group and
they will not receive pegcetacoplan treatment during the Controlled Portion;
biopsies will occur at Week 12.- Noncontrolled portion: Weeks 13-52 of the
study
- Group 1: Patients will continue to receive pegcetacoplan treatment; biopsies
will occur at Week 52.
- Group 2: Patients will receive pegcetacoplan treatment following their Week
12 renal allograft biopsy; biopsies will occur at Week 52.
• Follow-up period: a 8-week follow-up period
Part B, Long-Term Extension:
Any patient who, in the opinion of the investigator, is experiencing clinical
benefit from pegcetacoplan administration may participate in Part B, a
long-term extension, in order to continue to receive treatment with
pegcetacoplan until it is commercially available for the disease under study.
If invited to participate, the patient can enter Part B as soon as their
52-week treatment period has ended and does not need to participate in the
8-week follow-up period.
Intervention
• Investigational product, pegcetacoplan, will be administered as a 20-mL SC
infusion. Subjects will be trained on how to properly store, prepare, and
administer pegcetacoplan by the study team during your first 2 infusions. There
would be agreement on a dosing schedule with the study doctor, administering
pegcetacoplan on the same days, twice a week (for example, every Tuesday and
Friday) for the duration of the study. Additional instructions will be
available, and the study team will continue to assist subjects as needed.
The study center will supply pegcetacoplan which will need to be kept
refrigerated. Additionally, the study center will provide with all other
supplies.
Participants will be required to be vaccinated as follows on the basis of
Advisory Committee on
Immunization Practices (ACIP) recommendations for adults with complement
deficiencies
and/or immunocompromising conditions .
• N. meningitidis types A, C, W, and Y: First dose at least 2 weeks prior to
start of
pegcetacoplan with second dose 2 months later, and then boosters every 5 years.
• N. meningitidis type B (Bexsero): First dose at least 2 weeks prior to start
of
pegcetacoplan with a second dose after at least 1 month. First booster dose 1
year
later, and then additional booster doses every 2 to 3 years.
• S. pneumoniae: PCV13 and/or PPSV23 as per ACIP guidelines for adults with
immunocompromising conditions.
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 subcutaneous pegcetacoplan administration has been studied in
multiple Phase 2
and 3 studies for C3G and PNH, with an acceptable safety profile to date.
Nonetheless, a number
of safety monitoring practices are being employed by this protocol to ensure
patient safety,
including physical examination, vital signs monitoring, electrocardiograms
(ECGs), hematology
(including coagulation), serum chemistry, and 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 reported as an AE. The volume of blood planned for
collection from each patient over the course of the study will be minimized in
order to limit the
impact on the overall health of these anemic patients.
Systemic complement inhibition might predispose individuals to infections
caused by
encapsulated organisms, including Streptococcus pneumoniae, Neisseria
meningitidis, and
Haemophilus influenzae. Vaccinations against these organisms will be taken to
minimize
potential risk of infection. Use of prophylactic antibiotics is allowed, at the
discretion of the
investigator, and should take into consideration the level of
immunosuppression, complement
levels, and timing of vaccination relative to pegcetacoplan start, as well as
local practices. Body
temperature and vital signs will be monitored periodically, and relevant blood
parameters
monitored regularly throughout the study to assess for signs of infection. The
patient 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 based on
geographic location, Apellis will continue to evaluate the risks and benefits
around study conduct
on an ongoing and patient-by-patient basis.
100 5th Avenue, 3rd Floor N/A
Waltham MA 02451
US
100 5th Avenue, 3rd Floor N/A
Waltham MA 02451
US
Listed location countries
Age
Inclusion criteria
Individuals must meet all of the following criteria at screening visits to be
included in the study:
1. At least 18 years of age at screening
2. Must have clinical and pathologic evidence of recurrent C3G or IC-MPGN, as
evidenced by all of the following:
a. A diagnosis of C3G or IC-MPGN, with at least 2+ staining for C3c in the
renal allograft, confirmed by a central pathologist, based on the screening
renal allograft biopsy
b. C3G or IC-MPGN must be primary and not secondary to another condition (eg,
infection, malignancy, monoclonal gammopathy, autoimmunity, chronic
antibody-mediated rejection, chronic thrombotic microangiopathy, or a
medication)
3. Stable (not improving) or worsening disease, in the opinion of the
investigator, in the 2 months preceding the first dose of pegcetacoplan
4. eGFR >=15 mL/min/1.73 m2, calculated by the Chronic Kidney Disease-
Epidemiology Collaboration (CKD-EPI) creatinine equation for adults
5. No more than 50% glomerulosclerosis or interstitial fibrosis on the
screening renal biopsy
6. 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
7. Have required vaccinations against N. meningitides, 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 nonresponders to vaccination.
8. Women of childbearing potential, defined as any women who have experienced
menarche and who are not permanently sterile or postmenopausal, must have a
negative blood pregnancy test at screening (and negative urine pregnancy at
Visit 4) and must agree to use protocol defined methods of contraception from
screening through 12 weeks after receiving last dose of pegcetacoplan
9. Men must agree to use protocol-defined methods of contraception and agree to
refrain from donating semen from screening through 12 weeks after receiving
last dose of pegcetacoplan
10. Willing and able to provide written informed consent
11. Able to understand and willing to comply with all scheduled procedures and
other requirements of the study in the opinion of the investigator
12. Willing and able to self-administer pegcetacoplan or have an identified
caregiver who can perform the administration
Exclusion criteria
Individuals meeting any of the following criteria at screening or baseline are
ineligible to participate in this study:
1. Absolute neutrophil count <1000 cells/mm3 during screening (not including
Day 1)
2. Previous treatment with pegcetacoplan
3. Evidence of rejection on the screening renal allograft biopsy that requires
treatment
4. Diagnosis or history of HIV, hepatitis B, or hepatitis C infection or
positive serology at screening indicative of infection with any of these
viruses.
5. Weight more than 100 kg at screening
6. Hypersensitivity to pegcetacoplan or any of the excipients
7. History of menigococcal disease
8. 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
9. 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
10. 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 period
11. Women who are pregnant, or who are currently breastfeeding
12. Inability to cooperate or any condition that, in the opinion of the
investigator, could increase the subject's risk by participating in the study
or confound the outcome of the study
13. Evidence of drug or alcohol abuse or dependence, in the opinion of the
investigator
14. 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 | CTIS2024-511544-36-00 |
| EudraCT | EUCTR2020-002637-15-NL |
| CCMO | NL75809.091.20 |