TP10 Use in Patients With C3 Glomerulopathy (C3G)

• Register: ClinicalTrials.gov
• Last refreshed on: 7 November 2016
• Main ID: NCT02302755
• Date of registration: 05/11/2014
• Prospective Registration: No
• Primary sponsor: University of Iowa
• Public title: TP10 Use in Patients With C3 Glomerulopathy (C3G)
• Scientific title: A Pilot, Open-Label Single Center Trial of TP10 in Pediatric and Adult Patients With C3 Glomerulopathy (C3G)
• Date of first enrolment: November 2014
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02302755
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Richard JH Smith, MD
• Affiliation: University of Iowa Health Care

Key inclusion & exclusion 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



Age minimum: 4 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Dense Deposit Disease

Intervention(s)

Drug: TP10

Primary Outcome(s)

C3 serum measurements, serum C3 breakdown products, and/or alternative pathway (AP) complement activity. [Time Frame: 2 years]

Secondary Outcome(s)

Appropriate dose range and regimen for TP10. [Time Frame: 2 years]

Secondary ID(s)

UIowa

Source(s) of Monetary Support

Please refer to primary and secondary sponsors