Trial Outcomes & Findings for Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation (NCT NCT01895127)

Last Updated: 2017-09-21

Results Overview

Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Month 3

Results posted on

2017-09-21

Participant Flow

Participant milestones

Participant milestones
Measure	Standard of Care * Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP Immunoglobulin Plasmapheresis	Soliris (Eculizumab) * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Eculizumab
Screening STARTED	4	7
Screening COMPLETED	4	7
Screening NOT COMPLETED	0	0
Treatment Period (Week 0-Month 3) STARTED	3	7
Treatment Period (Week 0-Month 3) COMPLETED	3	7
Treatment Period (Week 0-Month 3) NOT COMPLETED	0	0
Month 3 Follow-up & Biopsy STARTED	3	7
Month 3 Follow-up & Biopsy COMPLETED	3	7
Month 3 Follow-up & Biopsy NOT COMPLETED	0	0
Long Term Follow-up (Month 3-12) STARTED	3	7
Long Term Follow-up (Month 3-12) COMPLETED	1	4
Long Term Follow-up (Month 3-12) NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care n=4 Participants * Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP Immunoglobulin Plasmapheresis	Soliris (Eculizumab) n=7 Participants * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Eculizumab	Total n=11 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants	7 Participants n=4 Participants	11 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	43.25 years n=93 Participants	43.29 years n=4 Participants	43.27 years n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	6 Participants n=4 Participants	8 Participants n=27 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Region of Enrollment United States	4 participants n=93 Participants	7 participants n=4 Participants	11 participants n=27 Participants

PRIMARY outcome

Timeframe: Month 3

Population: 1 subject in the SOC arm received rescue therapy, per protocol, with eculizumab following PP/IVIg. 1 subject in the Soliris arm received SOC therapy (PP/IVIg) following completion of Soliris treatment period. Both of these subjects received both SOC and Soliris treatment prior to Month 3 protocol biopsy so we have listed their outcome separately.

Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Outcome measures

Outcome measures
Measure	Standard of Care n=2 Participants * Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP Immunoglobulin Plasmapheresis	Soliris (Eculizumab) n=6 Participants * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Eculizumab	Standard of Care + Soliris (Eculizumab) n=2 Participants Subjects received both standard of care and Soliris treatment between Week 0 and Month 3
Percent Change in Estimated Glomerular Filtration (eGFR) Rate	-12.92 percent change in eGFR from wk 0 to mo 3 Interval -13.33 to -12.5	12.60 percent change in eGFR from wk 0 to mo 3 Interval -34.29 to 136.36	377.25 percent change in eGFR from wk 0 to mo 3 Interval 25.93 to 728.57

Adverse Events

Standard of Care

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Soliris (Eculizumab)

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard of Care n=4 participants at risk * Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP Immunoglobulin Plasmapheresis	Soliris (Eculizumab) n=7 participants at risk * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Eculizumab
Hepatobiliary disorders elevated serum alkaline phosphatase	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Renal and urinary disorders Acute kidney injury	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Immune system disorders Cellular Rejection	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	42.9% 3/7 • Number of events 3 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Immune system disorders Antibody-mediated rejection	75.0% 3/4 • Number of events 4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	71.4% 5/7 • Number of events 5 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Cardiac disorders Hypertension	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Cardiac disorders Hypotension	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Endocrine disorders Hyperglycemia	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Bacteremia	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Urinary Tract Infection	50.0% 2/4 • Number of events 3 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Renal and urinary disorders Pyelonephritis	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Bilateral Ear Infection	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Upper Respiratory Infection	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.

Other adverse events

Additional Information

Anil Chandraker

Brigham and Women's Hospital

Phone: 617-732-7412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Standard of Care n=4 participants at risk * Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP Immunoglobulin Plasmapheresis	Soliris (Eculizumab) n=7 participants at risk * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Eculizumab
Injury, poisoning and procedural complications headache	25.0% 1/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Blood and lymphatic system disorders Edema	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Gastrointestinal disorders Nausea	50.0% 2/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	42.9% 3/7 • Number of events 3 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Gastrointestinal disorders Emesis	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Gastrointestinal disorders Diarrhea	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Gastrointestinal disorders Abdominal Pain	50.0% 2/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Fever	75.0% 3/4 • Number of events 5 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Dizziness	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Renal and urinary disorders Nocturia	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Renal and urinary disorders Proteinuria	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Cardiac disorders Hypertension	25.0% 1/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Cardiac disorders Hypotension	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Chest Pain	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Fatigue	25.0% 1/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	28.6% 2/7 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Renal and urinary disorders Acute Kidney Injury	50.0% 2/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Endocrine disorders Hyperglycemia	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Cough	25.0% 1/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Hyperkalemia	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders elevated alkaline phosphatase	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
Infections and infestations Urinary Tract Infection	0.00% 0/4 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Back Pain	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Insomnia	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Weight Gain	25.0% 1/4 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	14.3% 1/7 • Number of events 1 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.
General disorders Tremor	25.0% 1/4 • Number of events 2 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.	0.00% 0/7 • Adverse event data was collected throughout the duration of the trial starting at screening through Month 12 for each subject.