Clinical trial NCT01791686: Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
Official title: A Pilot, Open-label, Multicenter Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Dense Deposit Disease
Membranoproliferative Glomerulonephritis Type II
C3 Glomerulonephritis
Keywords: Dense Deposit Disease
DDD
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-02-15
Enrollment: 1
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is evaluating the study drug (CDX-1135) in patients with dense deposit disease (DDD). The objective is to evaluate the safety and activity of repeated doses of CDX-1135 in pediatric and adult patients with DDD. After screening, eligible patients will be entered into the Induction Period. The Induction Period is up to 4 weeks. Following normalization of complement activity, patients will enter into the Maintenance Period.The total treatment duration is up to 26 weeks.


Eligibility criteria: Inclusion Criteria:

Among other criteria, patients must be

1. Patient and/or parent/legal guardian (as appropriate) must give written informed consent
2. Four (4) years of age or older
3. Must have DDD, confirmed by renal biopsy within 6 months of study enrollment (Confirmation by University of Iowa investigators is required). If the patient is post transplant, the repeat renal transplant biopsy must show C3 dominant glomerulonephritis, and the patient must have a history of known DDD in the native kidney
4. Signs of abnormal complement pathway activity
5. Serum creatinine level must be abnormal
6. Screening lab values criteria:

   1. Hgb ≥ 9.0 g/dL
   2. Platelets ≥ 100,000/mm\^3
   3. ALT and AST ≤ 3.0 x upper limit of normal
   4. C3 serum \<50% of the lower limit of normal
   5. 24 hour urine protein \>1000 mg/day, or urine protein:creatinine ratio \>1.0
7. Both male and female patients of childbearing potential enrolled must use adequate birth control during the trial and for 1 month after stopping study drug
8. Willing and able to comply with study procedures, including pre-study vaccinations (meningitis, haemophilus and pneumococci) and agree to a renal biopsy at Week 13 and at the end of the study
9. Any anti-proteinuric medications (eg, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers) must be at a stable dose for 4 weeks prior to first dose of CDX-1135

Exclusion Criteria:

Among other criteria, patients must not be

1. Dialysis or a low estimated glomerular filtration rate \<30 ml/min/1.73m\^2 over a 4-week period prior to Screening
2. Active or untreated systemic bacterial infection
3. Pregnant or lactating
4. Rituximab therapy (unless discontinued with B cell levels and immunoglobulin levels normalized by study entry)
5. Immunosuppressive therapies (except for low dose steroids \[≤10 mg per day\] given for non-DDD related conditions such as asthma). Exceptions will be made for renal transplant patients, who may receive any appropriate therapies as needed to maintain the transplant (i.e., to prevent rejection)
6. Treatment with any complement inhibitor within 3 months of study entry or any other investigational drug, device, or experimental procedure within 4 weeks prior to enrollment
7. For renal transplant patients only: histology findings of treatable rejection (i.e. that the usual transplant physician would seek to treat). Chronic allograft nephropathy is not exclusionary provided the patient's glomerular filtration rate meets other entry criteria
8. Preexisting condition with an association as a potential cause of DDD (i.e., Monoclonal Gammopathy of Undetermined Significance) or an alternate glomerular disease
9. Cancer except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer that the patient has been disease-free for ≥ 5 years
10. Myocardial infarction within 1 year of screening, congestive heart failure, arrhythmia persistent on medication at screening or chronic lung disease
11. Known HIV, Hepatitis B or Hepatitis C
12. Any medical or psychological condition that would increase the patient's risk by being in this study or would interfere with interpretation of the study

Primary outcomes:
measure: Safety
timeFrame: From first study drug dose for up to 26 weeks
measure: C3 and AP Normalization
timeFrame: Regular assessments from study start up to 26 weeks
Secondary outcomes:
measure: Duration of and time to normalize C3 and AP
timeFrame: Regular assessments from study start up to 26 weeks
measure: Renal Function
timeFrame: Regularly from study start up to 26 weeks
measure: Renal biopsy
timeFrame: Occurs up to 3 times from study start up to 26 weeks
measure: Immunogenicity
timeFrame: Regular assessments from study start up to 26 weeks
Other outcomes:
measure: CDX-1135 concentrations
timeFrame: Regular assessments from study start up to 26 weeks
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Carla Nester, MD, MSA
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Richard Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: