Trial Outcomes & Findings for A Pilot Study to Assess the Efficacy of Rituximab Therapy in Treatment Resistant FSGS (NCT NCT01573533)

Last Updated: 2020-02-10

Results Overview

The amount of protein in excreted urine measured by grams per day (g/day). Remission status defined by the following criteria at 12 months: * Complete Remission - Proteinuria \< 0.5 g/day * Partial Remission - Improvement in proteinuria by \> 50% and to a level between 0.5-3.5g/day * Incomplete Remission - Improvement in proteinuria equal to or \>50%, but residual proteinuria still \>3.5g/day

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Baseline, 12 months

Results posted on

2020-02-10

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Pilot Study to Assess the Efficacy of Rituximab Therapy in Treatment Resistant FSGS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab n=9 Participants Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Age, Continuous	37.4 years STANDARD_DEVIATION 16.2 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants
Region of Enrollment Canada	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 months

Outcome measures

Outcome measures
Measure	Rituximab n=9 Participants Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Changes in Proteinuria (With Stable Renal Function) Baseline	7.6 g/day Standard Deviation 4.67
Changes in Proteinuria (With Stable Renal Function) 12 months	7.27 g/day Standard Deviation 7.30

SECONDARY outcome

Timeframe: Baseline, 1, 3, 6 and 12 months

SuPAR concentrations will be determined by quantitative ELISA immunoassay reported in picograms per milliliters (pg/ml)

Outcome measures

Outcome measures
Measure	Rituximab n=9 Participants Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Change in suPAR Levels Baseline	4120 pg/ml Standard Deviation 1169
Change in suPAR Levels 1 month	3730 pg/ml Standard Deviation 1229
Change in suPAR Levels 3 month	4231 pg/ml Standard Deviation 1871
Change in suPAR Levels 6 month	4491 pg/ml Standard Deviation 2217
Change in suPAR Levels 12 month	3788 pg/ml Standard Deviation 1836

SECONDARY outcome

Timeframe: Baseline, 1, 3, 6, 12 months

To quantitatively examine the effect of FSGS patient sera on podocyte β3 integrin activity, a human podocyte cell line is cultured at 37 degrees Celsius for 14 days for complete differentiation. The cells are then incubated in 5-10% of FSGS patient serum for 24 hours with recombinant suPAR protein as a positive control. Cells are fixed with 4% paraformaldehyde (PFA) and proceeded for immunofluorescence staining for AP5 and paxillin. After immunostaining, confocal images are taken to quantify the AP5 and paxillin intensity for each sample treatment. Paxillin signal is used to correct AP5 signal. The relative AP5 signal (AP5/paxillin ratio) from each patient serum is then normalized against that of normal blood donor included in each assay for final report.

Outcome measures

Outcome measures
Measure	Rituximab n=9 Participants Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Change in Activation of Podocyte β3 Integrin 1 month	1.17 AP5/paxillin ratio Standard Deviation 0.17
Change in Activation of Podocyte β3 Integrin 3 month	1.13 AP5/paxillin ratio Standard Deviation 0.34
Change in Activation of Podocyte β3 Integrin Baseline	1.56 AP5/paxillin ratio Standard Deviation 0.59
Change in Activation of Podocyte β3 Integrin 6 month	1.15 AP5/paxillin ratio Standard Deviation 0.30
Change in Activation of Podocyte β3 Integrin 12 month	1.24 AP5/paxillin ratio Standard Deviation 0.27

SECONDARY outcome

Timeframe: 12 months

Total number of subjects with complete or partial remission following treatment using the following criteria: * Complete Remission - Proteinuria \< 0.5 g/day * Partial Remission - Improvement in proteinuria by \> 50% and to a level between 0.5-3.5g/day * Incomplete Remission - Improvement in proteinuria equal to or \>50%, but residual proteinuria still \>3.5g/day

Outcome measures

Outcome measures
Measure	Rituximab n=9 Participants Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Number of Subjects With Complete or Partial Remission Following Treatment	0 Participants

Adverse Events

Rituximab

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab n=9 participants at risk Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Infections and infestations Lung Infection	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Renal and urinary disorders Acute Kidney Infection	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.

Other adverse events

Other adverse events
Measure	Rituximab n=9 participants at risk Rituximab: Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
Renal and urinary disorders Relapse of Nephrotic Syndrome	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Infusion related reaction	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Sore Throat	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Cramps	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Dizziness	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Weakness	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Blood and lymphatic system disorders Neutropenia	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Rash	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
General disorders Headache	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Infections and infestations Nail Infection	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 1/9 • Number of events 1 • The study period during which all AEs and SAEs must be reported begins after informed consent is obtained and ends 30 days after study discontinuation/termination for each participant.

Additional Information

Fernando C. Fervenza, M.D., Ph.D.

Mayo Clinic

Phone: 507-266-1045

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place