Trial Outcomes & Findings for Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD (NCT NCT02176031)
NCT ID: NCT02176031
Last Updated: 2020-04-17
Results Overview
Graft-versus-host disease (GVHD) free survival is defined as achieving complete response without death or relapse or requiring secondary immunosuppressive therapy . Proportions are reported descriptively. GVHD-free survival was assessed using the Kaplan-Meier method.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Day 56
Results posted on
2020-04-17
Participant Flow
This study enrolled subjects with newly diagnosed acute gastrointestinal (GI) graft-versus-host-disease (GVHD) from 2 academic medical centers in the United States. The last patient completed the study in February 2019.
Participant milestones
| Measure |
Natalizumab
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert
|
|---|---|
|
Age, Continuous
|
63 Years
n=21 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
21 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Gastrointestinal Stage 1
|
4 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at HSCT
01 - Restricted
|
9 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Gastrointestinal Stage 2
|
5 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Gastrointestinal Stage 3
|
4 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Gastrointestinal Stage 4
|
8 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
No liver involvement
|
20 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Liver Stage 2
|
1 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
No skin involvement
|
17 Participants
n=21 Participants
|
|
Acute GVHD Staging (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Skin Stage 2
|
4 Participants
n=21 Participants
|
|
Disease Status of Underlying Malignancy at time of Hematopoietic Stem Cell Transplantation (HSCT)
First Complete Remission
|
9 Participants
n=21 Participants
|
|
Disease Status of Underlying Malignancy at time of Hematopoietic Stem Cell Transplantation (HSCT)
Second Complete Remission
|
5 Participants
n=21 Participants
|
|
Disease Status of Underlying Malignancy at time of Hematopoietic Stem Cell Transplantation (HSCT)
Relapsed Disease
|
2 Participants
n=21 Participants
|
|
Disease Status of Underlying Malignancy at time of Hematopoietic Stem Cell Transplantation (HSCT)
Progressive Disease
|
2 Participants
n=21 Participants
|
|
Disease Status of Underlying Malignancy at time of Hematopoietic Stem Cell Transplantation (HSCT)
Treatment Failure
|
3 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at HSCT
00 - Fully Active
|
2 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at HSCT
02 - Self Care
|
7 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at HSCT
03 - Capable of Limited Self Care
|
3 Participants
n=21 Participants
|
|
Conditioning Regimen
Myeloablative
|
3 Participants
n=21 Participants
|
|
Conditioning Regimen
Non-myeloablative
|
18 Participants
n=21 Participants
|
|
Donor type
Matched Unrelated
|
15 Participants
n=21 Participants
|
|
Donor type
Matched Related
|
5 Participants
n=21 Participants
|
|
Donor type
Mismatch Unrelated
|
1 Participants
n=21 Participants
|
|
Donor source
Bone marrow and Peripheral Blood Stem Cells
|
1 Participants
n=21 Participants
|
|
Donor source
Peripheral Blood Stem Cells
|
20 Participants
n=21 Participants
|
|
Acute GVHD Grading (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Overall Grade II
|
9 Participants
n=21 Participants
|
|
Acute GVHD Grading (Adapted from Glucksberg, H. et al. Transplantation 1974; 18:295)
Overall Grade III
|
12 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 56Graft-versus-host disease (GVHD) free survival is defined as achieving complete response without death or relapse or requiring secondary immunosuppressive therapy . Proportions are reported descriptively. GVHD-free survival was assessed using the Kaplan-Meier method.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
GVHD-free Survival Rate
|
33.3 percentage of patients
|
SECONDARY outcome
Timeframe: 28 Days, 56 Days* Complete Response (CR) is defined as resolution of all signs and symptoms of acute GVHD. * Very Good Partial Response (VGPR) is defined by no rash or residual erythematous rash involving less than 25% of the body surface, and total serum bilirubin concentration less than 2 mg/dL or less than 25% of baseline at enrollment and tolerating food or enteral feeding, predominantly formed stools, no overt gastrointestinal bleeding or abdominal cramping, and no more than occasional nausea and vomiting. * Partial Response (PR) is defined as an improvement of one stage in one or more organs without progression in any other organ. * Non-response (NR) is defined as no reduction in any GVHD organ staging. * Progression is defined as either new organ involvement on day +8 or thereafter, or increased organ specific symptoms sufficient to increase the organ stage by one or more or the initiation of an additional GVHD agent. * Overall Response Rate (ORR) is the sum of CR, VGPR, and PR.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Graft-verus-host Disease (GVHD) Response Rate
Very Good Partial Response at Day 28
|
2 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Overall Response at Day 28
|
12 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Complete Response at Day 28
|
7 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Partial Response at Day 28
|
3 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Non-response/Progression of GVHD at Day 28
|
7 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Overall Response at Day 56
|
11 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Complete Response at Day 56
|
7 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Very Good Partial Response at Day 56
|
2 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Partial Response at Day 56
|
2 Participants
|
|
Graft-verus-host Disease (GVHD) Response Rate
Non-response/Progression of GVHD at Day 56
|
6 Participants
|
SECONDARY outcome
Timeframe: Day 28, Day 56Gastrointestinal (GI) acute graft-versus-host disease (GVHD) Response is defined by complete response, very good partial response, or partial response in signs and symptoms of GI aGVHD.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
GI aGVHD Response Rate
Overall response rate for GI GVHD at Day 28
|
57 percentage of patients
|
|
GI aGVHD Response Rate
Overall response rate for GI GVHD at Day 56
|
52 percentage of patients
|
SECONDARY outcome
Timeframe: 2 yearsOverall survival (OS) is defined from the date of natalizumab infusion to death or censored at last clinical evaluation. OS was estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Overall Survival (OS) Rate
|
43 percentage of patients
|
SECONDARY outcome
Timeframe: by Day 28Number of subjects who experienced graft-versus-host disease (GVHD) flares requiring therapy after initial complete response (CR) or partial response (PR) by day 28 after the first dose of Natalizumab.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Rate of GVHD Flares
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 28, 56, and 100Median percentage steroid dose was reduced at Day 28, Day 56, and Day 100 in comparison to steroid dose at first administration of Natalizumab.
Outcome measures
| Measure |
Natalizumab
n=21 Participants
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
Median reduction in steroid dose at day 28
|
42 percentage of steroid dose
Interval 20.0 to 50.0
|
|
Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
Median reduction in steroid dose at day 56
|
71 percentage of steroid dose
Interval 60.0 to 81.0
|
|
Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
Median reduction in steroid dose at day 100
|
85 percentage of steroid dose
Interval 63.0 to 93.0
|
Adverse Events
Natalizumab
Serious events: 8 serious events
Other events: 19 other events
Deaths: 12 deaths
Serious adverse events
| Measure |
Natalizumab
n=21 participants at risk
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Cardiac disorders
Hypotension
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Cardiac disorders
Paroxysmal atrial tachycardia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Nervous system disorders
Subarachnoid hemorrhage
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Nervous system disorders
Intraparenchymal hemorrhage
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Hepatobiliary disorders
Hepatic failure
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Stenotrophomonas bacteremia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Klebsiella infection
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Sepsis
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
CMV viremia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
C. diff colitis
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Renal and urinary disorders
Acute kidney injury
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopneumonia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Respiratory, thoracic and mediastinal disorders
Diffuse alveolar hemorrhage
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
Other adverse events
| Measure |
Natalizumab
n=21 participants at risk
Natalizumab-
* (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
* At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
* If participants have no response after one dose, they will be not be given a second dose.
* Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
* Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
* Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - other
|
19.0%
4/21 • Number of events 4 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Eye disorders
Blurred vision
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
3/21 • Number of events 3 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Cecal infection
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Colitis
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Diarrhea
|
28.6%
6/21 • Number of events 6 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Duodenal ulcer
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - other
|
19.0%
4/21 • Number of events 4 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Gastroparesis
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Gastrointestinal disorders
Nausea
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
General disorders
Edema limbs
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
General disorders
Localized edema
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
General disorders
Multi-organ failure
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Hepatobiliary disorders
Hepatobiliary disorders - other
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Hepatobiliary disorders
Portal hypertension
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Enterocolitis infectious
|
14.3%
3/21 • Number of events 3 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Infections and infestations - other
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Small intestine infection
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Infections and infestations
Urinary tract infection
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Weight loss
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Alanine aminotransferase increased
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Aspartate aminotransferase increased
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Blood bilirubin increased
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Investigations - other
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Investigations
Platelet count decreased
|
14.3%
3/21 • Number of events 3 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
28.6%
6/21 • Number of events 6 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - other
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Nervous system disorders
Encephalopathy
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Nervous system disorders
Headache
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Nervous system disorders
Nervous system disorders - other
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Renal and urinary disorders
Acute kidney injury
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Reproductive system and breast disorders
Genital edema
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Renal and urinary disorders
Hoarseness
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.8%
1/21 • Number of events 1 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
|
Vascular disorders
Hypertension
|
9.5%
2/21 • Number of events 2 • 1 year
All grade 2 related and unexpected and all grade 3 and higher adverse events experienced by participants were collected from the time of the first dose of study treatment, through the study and until the final study visit. Grade 4 skin rash, diarrhea and increased bilirubin were expected adverse events as a result of acute graft-versus-host disease (aGVHD) and did not require reporting. All positive John Cunningham (JC) viral loads required reporting regardless of grade.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place