Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS

NCT00464321 | Completed Phase 1 DMC

• 1 other identifier: GC1008FSGS00505
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 9

Brief Summary

This study will investigate whether GC1008, an antibody which neutralizes TGF-beta, is safe in treating patients with the disease called focal segmental glomerulosclerosis (FSGS). The highest dose without excessive side effects will be investigated. Tests will determine how long GC1008 is in the body and how it is excreted.

Conditions

Focal Segmental Glomerulosclerosis

Outcome Measures

Primary Outcomes (2)

• To determine Safety and tolerability of single dose infusions of GC1008 in patients with treatment resistant idiopathic FSGS and nephrotic range proteinuria

  up to 2 years

• Pharmacokinetics of GC1008 following a single dose infusion

  up to 2 years

Secondary Outcomes (1)

• To investigate Effect of single dose infusions of GC1008 on biomarkers of clinical efficacy.

  up to 2 years

Study Arms (4)

Cohort A

EXPERIMENTAL

Dose Group

Biological: GC1008

Cohort B

EXPERIMENTAL

Dose Group

Biological: GC1008

Cohort C

EXPERIMENTAL

Dose Group

Biological: GC1008

Cohort D

EXPERIMENTAL

Dose Group

Biological: GC1008

Interventions

GC1008 BIOLOGICAL

1 mg/kg, IV infusion on Day 0 and monitored over 24 hours. Post infusion for safety up to 112 days.

Cohort A

Eligibility Criteria

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

You may qualify if:

• GFR≥25ml/min/1.73m2 calculated by the MDRD equation
• Urinary total protein: creatinine ratios \>200mg/mmol derived from the average of 2 first morning voids taken during screening period
• Biopsy confirmed as idiopathic FSGS by a central reviewer
• Treatment resistance. NOTE:Patients to have received minimum 6 week course of steroids or immunosuppressant
• If receiving treatment with an ACEi and/or ARB dose to be stable for a minimum of 4 weeks prior to randomization
• Influenza vaccine (according to season)
• Negative screening per American Cancer Society (ACS) 2003 guidelines, as appropriate to patient demographics and clinical status

You may not qualify if:

• Secondary FSGS
• steroid resistant patients who are unable to reduce their steroid dose to \<10mg/day of prednisolone or equivalent 4 weeks prior to study dosing day
• Positive serology for serious infections (including but not limited to infection with Hep B or C, HIV)
• Concomitant illnesses:Diabetes Type I; Cardiac or Hepatic disease, HIV; Cancer, precancerous state (eg familial adenomatous polyposis; Any condition requiring treatment with other immunosuppressant drugs within 4 weeks prior to dosing day or during the course of the study
• Pre-existing oral-pharyngeal disease (dental carries and other minor dental disease are acceptable)
• Haemoglobin level of \<9.0g/dL prior to dosing
• Treatment with coumadin, anti-vitamin K analogues or low molecular weight heparins. Patients must have stopped treatment a minimum of four weeks prior to receiving study medication.
• Patients requiring ongoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Patients must have stopped treatment a minimum of four weeks prior to receiving study medication.
• Patients who have had surgery/fracture within 3 months prior to dosing day
• History of cancer unresolved within 5 years prior to screening or a known precancerous state; or any form of skin cancer either current or past history
• Women who are pregnant, lactating or who plan to become pregnant within 4 months of infusion
• Women of childbearing potential unless taking medically acceptable contraceptive
• Men with female partners of childbearing potential unless they are taking medically acceptable contraceptive precautions
• Use of any investigation drug administered as part of a clinical trial within 4 weeks prior to commencing screening
• Other clinically significant, uncontrolled medical condition that in the investigator's opinion may interfere with the assessment or follow-up

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (9)

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

New Hyde Park, New York, 11042-1433, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Düsseldorf, Germany

Location

Unknown Facility

Solingen, Germany

Location

Unknown Facility

Bergamo, Italy

Location

Unknown Facility

Cambridge, United Kingdom

Location

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

fresolimumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 20, 2007
• First Posted: April 23, 2007
• Study Start: May 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: February 1, 2010
• Last Updated: March 19, 2014

Record last verified: 2014-03

Locations

US (4); IT (1); DE (3); GB (1)