Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease

NCT01791686 | Terminated Phase 1 DMC

• 1 other identifier: CDX1135-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Dense Deposit Disease; Membranoproliferative Glomerulonephritis Type II; C3 Glomerulonephritis

Keywords

Dense Deposit Disease; DDD

Outcome Measures

Primary Outcomes (2)

• Safety

  * Incidence and severity of adverse events (AE) will be assessed at every visit. AEs and serious adverse events (SAEs) will be assessed from the first dose of study drug through 33 days after the last dose * To evaluate the safety of repeated dosing in patients with DDD. Safety will be assessed based on changes in clinical laboratory tests, physical exams, vital signs, ophthalmic exams and ECGs \[for patients ≥ 35 years of age\].

  From first study drug dose for up to 26 weeks

• C3 and AP Normalization

  The proportion of patients with normalization of serum C3, serum C3 breakdown products, or alternative pathway (AP) complement activity. These blood tests will be assessed on each dosing day and upon Study Completion /Termination.

  Regular assessments from study start up to 26 weeks

Secondary Outcomes (4)

• Duration of and time to normalize C3 and AP

  Regular assessments from study start up to 26 weeks

• Renal Function

  Regularly from study start up to 26 weeks

• Renal biopsy

  Occurs up to 3 times from study start up to 26 weeks

• Immunogenicity

  Regular assessments from study start up to 26 weeks

Other Outcomes (1)

• CDX-1135 concentrations

  Regular assessments from study start up to 26 weeks

Study Arms (1)

Dense Deposit Disease

EXPERIMENTAL

► Induction Period Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri). There will be two doses of 5 mg/kg, with intrapatient dose-escalation in 5 mg/kg increments up to a maximum dose of 30 mg/kg. This period may last up to 8 weeks. ► Maintenance Period The starting dose for CDX-1135 Maintenance will be the same dose level as the last dose during the Induction Period; however, the Maintenance Period allows for dose decrease to 2 mg/kg, which is lower than the starting dose in the Induction Period. Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri) for up to a total of 26 weeks.

Drug: CDX-1135

Interventions

CDX-1135 DRUG

Also known as: TP10, sCR1

Dense Deposit Disease

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Among other criteria, patients must be
• Patient and/or parent/legal guardian (as appropriate) must give written informed consent
• Four (4) years of age or older
• 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
• Signs of abnormal complement pathway activity
• Serum creatinine level must be abnormal
• Screening lab values criteria:
• Hgb ≥ 9.0 g/dL
• Platelets ≥ 100,000/mm\^3
• ALT and AST ≤ 3.0 x upper limit of normal
• C3 serum \<50% of the lower limit of normal
• hour urine protein \>1000 mg/day, or urine protein:creatinine ratio \>1.0
• 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
• 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
• 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

You may not qualify if:

• Among other criteria, patients must not be
• Dialysis or a low estimated glomerular filtration rate \<30 ml/min/1.73m\^2 over a 4-week period prior to Screening
• Active or untreated systemic bacterial infection
• Pregnant or lactating
• Rituximab therapy (unless discontinued with B cell levels and immunoglobulin levels normalized by study entry)
• 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)
• 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
• Preexisting condition with an association as a potential cause of DDD (i.e., Monoclonal Gammopathy of Undetermined Significance) or an alternate glomerular disease
• 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
• Myocardial infarction within 1 year of screening, congestive heart failure, arrhythmia persistent on medication at screening or chronic lung disease
• Known HIV, Hepatitis B or Hepatitis C
• 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

Sponsors & Collaborators

• Celldex Therapeutics: lead

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Study Officials

• Carla Nester, MD, MSA

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Richard Smith, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: February 15, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 7, 2014

Record last verified: 2014-03

Locations

US (1)