A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy
- Conditions
- C3 Glomerulopathy10038430
- Registration Number
- NL-OMON48649
- Lead Sponsor
- Chemocentryx
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
1. Biopsy-proven C3G, either DDD or C3GN, with or without a renal transplant,
and with the following observations upon renal biopsy taken within 12 weeks
prior to screening or during screening:
a. >=2-levels of magnitude greater staining of C3 than any combination of IgG,
IgM, IgA, kappa and lambda light chains, and C1q by immunohistochemistry, and
b. evidence of proliferative glomerulonephritis (mesangial hypercellularity of
greater than 3 mesangial cells per mesangial area and/or endocapillary
hypercellularity defined as an increased number of cells within glomerular
capillary lumina, causing luminal narrowing) based on light microscopy, and
c. confirmation of the presence of electron dense deposits in the glomeruli on
electron microscopy corresponding with the C3 immunofluorescence positivity;
2. Male or female patients, aged at least 18 years; where approved, adolescents
(12-17 year old) may be enrolled; female patients of childbearing potential
(i.e., those who have experienced menarche and who is not permanently sterile
or postmenopausal, defined as at least 12 consecutive months with no menses
without an alternative medical cause) may participate if adequate contraception
is used during, and for at least the three months after study completion; Male
patients with partners of childbearing potential may be excluded if they plan
to father a child during the study; Adequate contraception is defined as
resulting in a failure rate of less than 1% per year (combined estrogen and
progestogen [oral, intravaginal, or transdermal], or progestogen-only hormonal
contraception (oral, injectable, or implantable), intra-uterine device,
intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized
partner, or true sexual abstinence, i.e., in line with the preferred and usual
lifestyle of the patient. In addition, a barrier method (i.e., cervical cap,
diaphragm or condom) must be used during intercourse between a male patient and
a female of child-bearing potential;
3. Willing and able to give written Informed Consent and to comply with the
requirements of the study protocol; written Assent and Informed Consent must be
obtained from the legal guardian in accordance with regional laws or
regulations for patients 12 to 17 years of age; and
4. Judged to be otherwise fit for the study by the Investigator, based on
medical history, physical examination, and clinical laboratory assessments.
Patients with clinical laboratory values that are outside of normal limits
(other than those specified in the Exclusion Criteria) and/or with other
abnormal clinical findings that are judged by the Investigator not to be of
clinical significance, may be entered into the study. At sites in which
adolescents are allowed to be enrolled, the Investigator assures that the
adolescent patient is willing and able to ingest the size 0 study drug.
1. Pregnant or nursing;
2. Tubulointerstitial fibrosis appears to be more than 50% based on standard
assessment using trichrome staining of the renal biopsy;
3. Use of eculizumab or another anti-C5 antibody within 26 weeks prior to
dosing;
4. Secondary C3 disease, e.g., infection-associated disease, or associated with
another systemic or autoimmune disease; presence of a monoclonal spike on serum
or urine protein electrophoresis or immunofixation assay;
5. Currently on dialysis or likely will require dialysis within 7 days after
screening;
6. History or presence of any form of cancer within the 5 years prior to
screening, with the exception of excised basal cell or squamous cell carcinoma
of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ
that has been excised or resected completely and is without evidence of local
recurrence or metastasis;
7. Positive HBV, HCV, or HIV viral screening test indicative of acute or
chronic infection;
8. Evidence of tuberculosis based on interferon γ release assay (IGRA),
tuberculin purified protein derivative (PPD) skin test, or chest radiography
done at screening or within 6 weeks prior to screening; a CT scan or chest
X-ray are not mandatory if evidence of tuberculosis was excluded by any of the
other methods specified above;
9. Active uncontrolled infection;
10. WBC count less than 3500/mL, or neutrophil count less than 1500/mL, or
lymphocyte count less than 500/mL before start of dosing;
11. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin
>3 x the upper limit of normal before start of dosing;
12. Currently using a strong inducer of the cytochrome P450 3A4 (CYP3A4)
enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St.
John*s wort;
13. Known hypersensitivity to avacopan or inactive ingredients of the avacopan
capsules (including gelatin, polyethylene glycol, or Cremophor) or inability to
swallow the capsules;
14. Participated in any clinical study of an investigational product within 30
days prior to screening or within 5 half-lives after taking the last dose; and
15. History or presence of any medical condition (for example: contraindication
to local anesthesia required for renal biopsy, or recurring serious infections)
or disease which, in the opinion of the Investigator, may place the patient at
unacceptable risk for study participation.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the percent change from baseline to Week 26 in<br /><br>the C3G Histologic Index for disease activity. </p><br>
- Secondary Outcome Measures
Name Time Method