TP10 Use in Patients With C3 Glomerulopathy (C3G)

• Status: Withdrawn
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety of repeated TP10 dosing in pediatric and adult patients with C3G and to evaluate the activity of TP10 in pediatric and adult patients with C3G, as measured by the proportion of patients with normalization of serum C3, serum C3 breakdown products, or alternative pathway (AP) complement activity.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Iowa

Criteria

Inclusion Criteria:

1. Patient must have C3G as confirmed by renal biopsy within six months of 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 C3G in the native kidney.

2. C3 serum must be less than 75% of the lower limit of normal.

3. Signs of alternative pathway dysregulation must be present. C3 breakdown products or C3Nef activity must be detectable in plasma using assays described and validated at the University of Iowa

4. Serum creatinine level must be abnormal (>97 percentile for age or <80 ml/min using the Cockroft Gault equation for adults).

5. Must have either 24 hour urine protein >1000 mg/day, or urine protein:creatinine ratio >1.0.

6. Screening laboratory values must meet the following criteria:

• hemoglobin ≥ 9.0 g/dL

• platelet count ≥ 100,000/mm3

• alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 x ULN

7. Must use adequate birth control measures.

8. Patient must be willing and able to comply with study procedures including vaccination against meningitis, haemophilus and pneumococci at least 2 weeks prior to starting the Induction Period and agree to a renal biopsy at the conclusion of the study.

9. Any anti-proteinuric medications (eg, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers) must be at a stable dose for at least four weeks prior to first dose of TP10.

Exclusion Criteria:

1. Dialysis or patients with an estimated glomerular filtration rate (eGFR; using Cockroft Gault equation) of less than 30 ml/min/1.73 m2 for over a four-week period prior to the Screening Period

2. Presence or suspicion of active or untreated systemic bacterial infection that in the opinion of the investigator precludes treatment with TP10

3. Pregnancy or lactation

4. Rituximab therapy, unless discontinued with B cell levels and immunoglobulin levels normalized by study entry

5. Patients receiving immunosuppressive therapies (except for low dose steroids [≤10 mg of prednisone or equivalent per day] given for non-C3G related conditions such as asthma). Patients receiving steroids for C3G must complete a taper prior to study entry. 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. Receipt of any complement inhibitor within 2 months of study entry

7. Receipt of any other investigational drug or device or experimental procedures beginning four weeks prior to study enrollment

8. 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 GFR meets other entry criteria.

9. A preexisting condition with a reported association as a potential cause of C3G (i.e., Monoclonal Gammopathy of Undetermined Significance [MGUS]) or an alternate glomerular disease that may interfere with the interpretation of study results

10. Malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease-free for ≥ 5 years

11. Patients with myocardial infarction (MI) within 1 year of screening, congestive heart failure, arrhythmia persistent on medication at screening or clinically evident chronic lung disease

12. Known Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C infection

13. Any medical or psychological condition that, in the opinion of the investigator, would increase the patient's risk by participation in this study or would interfere with interpretation of the study

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