Trial Outcomes & Findings for Belatacept to Prevent Organ Rejection in Kidney Transplant Patients (NCT NCT00346151)

NCT ID: NCT00346151

Last Updated: 2017-04-21

Results Overview

Cumulative incidence of acute rejection\[1\] at 6 months post-transplant based on local pathology biopsy reads 1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

6 months post-transplant

Results posted on

2017-04-21

Participant Flow

Two centers in the United States enrolled five recipients of non-human leukocyte antigen (HLA)-identical living-donor-related renal transplants between January 2007 and January 2009.

At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and sign the informed consent form.

Participant milestones

Participant milestones
Measure
Belatacept
Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
Overall Study
STARTED
5
Overall Study
COMPLETED
2
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Belatacept
Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
Overall Study
Withdrawal by Subject
3

Baseline Characteristics

Belatacept to Prevent Organ Rejection in Kidney Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
5 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Age, Continuous
50.4 years
STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
Region of Enrollment
United States
5 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 months post-transplant

Population: Intent to Treat

Cumulative incidence of acute rejection\[1\] at 6 months post-transplant based on local pathology biopsy reads 1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Acute Rejection at 6-Months
3 Participants

SECONDARY outcome

Timeframe: 12 months post-transplant

Population: Intent to Treat Sample participants not terminating prior to 12 months.

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=4 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Participant Survival at 12 Months Post-Transplant
4 Participants

SECONDARY outcome

Timeframe: 12 months post-transplant

Population: Intent to Treat Sample

Incidence of acute rejection\[1\] at 12 months post-transplant 1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Acute Rejection at 12-Months
4 Participants

SECONDARY outcome

Timeframe: 48 months

Population: Intent to treat sample that initiated sirolimus withdrawal

Time from transplantation to initiation of sirolimus withdrawal.

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=1 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Tolerance Induction
391 Days

SECONDARY outcome

Timeframe: 24 weeks post-transplant

Population: Intent to Treat Sample

GFR utilizing clearance of iothalamate. GFR is an index of level of kidney function. A higher value means better kidney function.

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=3 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks
62.0 mL/min/1.73m^2
Standard Deviation 8.5

SECONDARY outcome

Timeframe: 12 months post-transplant

Population: Intent to treat sample participants not terminating prior to 12 months

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=4 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Graft Survival at 12 Months Post-transplant
4 Participants

SECONDARY outcome

Timeframe: Transplantation until rejection occurs (participants followed up to four years post-transplantation)

Population: Intent to treat sample participants with rejection

Time (days) from transplant to occurrence of acute rejection\[1\] 1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=4 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Time From Transplant to Acute Rejection
15 Days
Full Range 95.4 • Interval 1.0 to 200.0

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Proportion of participants who experienced acute rejection\[1\] requiring antilymphocyte therapy 1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection
0 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Proportion of participants who experienced infections post-transplant. Participants were checked for any type of opportunistic infection at all study visits post-transplantation (up to 4 years post-transplantation)

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Post-transplant Infections
4 Participants

SECONDARY outcome

Timeframe: Start of study to end of study

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Wound Complications
0 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Malignancies
0 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With a Sirolimus Associated Adverse Event
5 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Chronic Allograft Nephropathy
0 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Delayed Graft Function
0 Participants

SECONDARY outcome

Timeframe: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Population: Intent to Treat Sample

Outcome measures

Outcome measures
Measure
Immunosuppression Withdrawal
n=5 Participants
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Proportion of Participants With Post-transplant Diabetes Mellitus
1 Participants

Adverse Events

Immunosuppression Withdrawal

Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Immunosuppression Withdrawal
n=5 participants at risk
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Blood and lymphatic system disorders
Lymphocele
20.0%
1/5 • Number of events 1
Immune system disorders
Kidney transplant rejection
80.0%
4/5 • Number of events 5
Respiratory, thoracic and mediastinal disorders
Lung infiltration
20.0%
1/5 • Number of events 1

Other adverse events

Other adverse events
Measure
Immunosuppression Withdrawal
n=5 participants at risk
Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal
Blood and lymphatic system disorders
Anaemia
60.0%
3/5 • Number of events 3
Blood and lymphatic system disorders
Leukopenia
40.0%
2/5 • Number of events 3
Blood and lymphatic system disorders
Thrombocythaemia
20.0%
1/5 • Number of events 1
Cardiac disorders
Palpitations
20.0%
1/5 • Number of events 1
Ear and labyrinth disorders
Middle ear inflammation
20.0%
1/5 • Number of events 1
Endocrine disorders
Hyperparathyroidism
20.0%
1/5 • Number of events 1
Eye disorders
Vision blurred
20.0%
1/5 • Number of events 1
Gastrointestinal disorders
Abdominal pain
20.0%
1/5 • Number of events 2
Gastrointestinal disorders
Abdominal pain upper
20.0%
1/5 • Number of events 1
Gastrointestinal disorders
Constipation
40.0%
2/5 • Number of events 2
Gastrointestinal disorders
Diarrhoea
80.0%
4/5 • Number of events 4
Gastrointestinal disorders
Mouth ulceration
40.0%
2/5 • Number of events 2
Gastrointestinal disorders
Nausea
80.0%
4/5 • Number of events 5
Gastrointestinal disorders
Vomiting
20.0%
1/5 • Number of events 1
General disorders
Asthenia
20.0%
1/5 • Number of events 1
General disorders
Fatigue
20.0%
1/5 • Number of events 4
General disorders
Malaise
20.0%
1/5 • Number of events 1
General disorders
Oedema
60.0%
3/5 • Number of events 4
General disorders
Oedema peripheral
20.0%
1/5 • Number of events 1
General disorders
Pyrexia
40.0%
2/5 • Number of events 2
Infections and infestations
BK virus infection
40.0%
2/5 • Number of events 2
Infections and infestations
Cytomegalovirus viraemia
20.0%
1/5 • Number of events 3
Infections and infestations
Diverticulitis
20.0%
1/5 • Number of events 1
Infections and infestations
Epstein-Barr viraemia
20.0%
1/5 • Number of events 1
Infections and infestations
Folliculitis
20.0%
1/5 • Number of events 1
Infections and infestations
Herpes virus infection
20.0%
1/5 • Number of events 4
Infections and infestations
Oral infection
20.0%
1/5 • Number of events 1
Infections and infestations
Upper respiratory tract infection
20.0%
1/5 • Number of events 1
Infections and infestations
Urinary tract infection
40.0%
2/5 • Number of events 3
Infections and infestations
Vulvovaginal mycotic infection
20.0%
1/5 • Number of events 1
Injury, poisoning and procedural complications
Graft dysfunction
20.0%
1/5 • Number of events 2
Injury, poisoning and procedural complications
Incision site pain
40.0%
2/5 • Number of events 2
Injury, poisoning and procedural complications
Medical device pain
20.0%
1/5 • Number of events 1
Injury, poisoning and procedural complications
Procedural nausea
20.0%
1/5 • Number of events 2
Investigations
Blood creatinine increased
20.0%
1/5 • Number of events 1
Investigations
Weight increased
40.0%
2/5 • Number of events 3
Metabolism and nutrition disorders
Acidosis
20.0%
1/5 • Number of events 1
Metabolism and nutrition disorders
Hypercholesterolaemia
20.0%
1/5 • Number of events 1
Metabolism and nutrition disorders
Hyperglycaemia
20.0%
1/5 • Number of events 1
Metabolism and nutrition disorders
Hyperphosphataemia
20.0%
1/5 • Number of events 1
Metabolism and nutrition disorders
Hypocalcaemia
40.0%
2/5 • Number of events 2
Metabolism and nutrition disorders
Hypokalaemia
20.0%
1/5 • Number of events 1
Metabolism and nutrition disorders
Hypomagnesaemia
60.0%
3/5 • Number of events 3
Metabolism and nutrition disorders
Hypophosphataemia
40.0%
2/5 • Number of events 2
Metabolism and nutrition disorders
Metabolic acidosis
20.0%
1/5 • Number of events 1
Musculoskeletal and connective tissue disorders
Arthralgia
20.0%
1/5 • Number of events 2
Musculoskeletal and connective tissue disorders
Flank pain
20.0%
1/5 • Number of events 1
Musculoskeletal and connective tissue disorders
Pain in extremity
20.0%
1/5 • Number of events 2
Nervous system disorders
Headache
20.0%
1/5 • Number of events 1
Nervous system disorders
Tremor
20.0%
1/5 • Number of events 1
Psychiatric disorders
Anxiety
20.0%
1/5 • Number of events 1
Psychiatric disorders
Insomnia
20.0%
1/5 • Number of events 2
Renal and urinary disorders
Dysuria
20.0%
1/5 • Number of events 1
Renal and urinary disorders
Haematuria
20.0%
1/5 • Number of events 1
Renal and urinary disorders
Renal disorder
20.0%
1/5 • Number of events 1
Reproductive system and breast disorders
Benign prostatic hyperplasia
20.0%
1/5 • Number of events 1
Reproductive system and breast disorders
Scrotal oedema
20.0%
1/5 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Cough
20.0%
1/5 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
40.0%
2/5 • Number of events 3
Skin and subcutaneous tissue disorders
Alopecia
20.0%
1/5 • Number of events 2
Skin and subcutaneous tissue disorders
Dry skin
20.0%
1/5 • Number of events 1
Skin and subcutaneous tissue disorders
Ecchymosis
40.0%
2/5 • Number of events 2
Skin and subcutaneous tissue disorders
Rash
20.0%
1/5 • Number of events 1
Vascular disorders
Hypertension
40.0%
2/5 • Number of events 2
Vascular disorders
Hypotension
20.0%
1/5 • Number of events 1

Additional Information

Director, Clinical Research Program

DAIT/NIAID

Phone: 301-594-7669

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place