Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00445913
Status:
COMPLETED
Last Update Posted:
2016-02-15
First Post:
2007-03-07
Brief Title:
Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression A Safety Study
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression A Safety Study
Status:
COMPLETED
Status Verified Date:
2016-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The proposed studies describe a randomized trial to evaluate the safety of a new diabetes-suppressive cell vaccine consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulatory molecules immunoregulatory DC iDC The hypothesis to be tested in this study is that iDC are safe and without toxicity in established type 1 diabetic patients
Fifteen 15 individuals exhibiting fully-established insulin-dependent type 1 diabetics without any diabetes-related complications infectious disease or other medical anomaly will be enrolled to establish safety of the approach 715 volunteers will be administered autologous control dendritic cells and 815 will be administered iDC The study is anticipated to be complete by twelve 12 months
Currently other than a humanized anti-CD3 antibody with considerable side effects there is no other means to reverse new-onset type 1 diabetes These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to perhaps reverse it early on in the clinical process
Fifteen 15 individuals exhibiting fully-established insulin-dependent type 1 diabetics without any diabetes-related complications infectious disease or other medical anomaly will be enrolled to establish safety of the approach 715 volunteers will be administered autologous control dendritic cells and 815 will be administered iDC The study is anticipated to be complete by twelve 12 months
Currently other than a humanized anti-CD3 antibody with considerable side effects there is no other means to reverse new-onset type 1 diabetes These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to perhaps reverse it early on in the clinical process
Detailed Description:
In this study volunteers with established type 1 diabetes that requires insulin replacement who do not exhibit any diabetes-related complications or any other clinical pathology will first undergo complete physical biochemical and immunological evaluation Monocyte-derived autologous dendritic cells will be obtained following leukapheresis The dendritic cells will be treated ex vivo with the antisense oligonucleotides and cryopreserved in aliquots for subsequent intradermal administration into sites closest to the physical location of the pancreas inside the body Physiologic biologic and immunologic responses to the dendritic cell vaccine will be evaluated over the period of the trial The first group of volunteers will receive autologous dendritic cells without any ex vivo treatment 715 and the second group will be administered iDC 815 If there is no evidence of toxicity or adverse events associated with the dendritic cell vaccine and only upon FDA and IRB approval we will initiate a new study comparing efficacy of control DC and iDC in improving glycemia and reversing autoimmunity in new-onset patients
Currently other than a humanized anti-CD3 antibody with considerable side effects there is no other means to reverse new-onset type 1 diabetes These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to possibly reverse it early on in the clinical process
We propose to ascertain the safety of autologous dendritic cells treated ex vivo with antisense oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulatory molecules we term these cells immunoregulatory dendritic cells iDC first in volunteers with established type 1 diabetes
Personality traits and emotional stability have been linked to treatment adherence in other medical populations eg Christensen et al 2002 Dew et al 2001 In that adherence to this protocol eg remaining in the study by this small sample will impact significantly on results and that the treatment itself may affect mood we will assess personality traits at baseline and monitor mood throughout the study period
22 Significance of the studies We do not anticipate any safety issues with this approach but we must be cautious at all levels given that this is immunomodulation therapy At the very least data will be obtained on whether the success we have observed with the iDC in NOD mice can be eventually adapted in other protocols aimed to restore normoglycemia or improve glycemic control along with increased prevalence of putative immunoregulatory T cells in recently-diagnosed humans
30 RESEARCH DESIGN AND METHODS
31 DrugDevice Information 311 Autologous Dendritic Cells Control Dendritic Cells These are cells derived from the leukapheresis product of each patient The leukapheresis product is processed inside an ElutraAastromTM cell elutriation system Refer to appended SOP CPL-0158 and CPL-0166 to obtain immature dendritic cells The final autologous product after these procedures is termed Control Dendritic Cells
312 Autologous Immunoregulatory Diabetes-Suppressive Dendritic Cells iDC We have submitted an IND application appended to the FDA to cover a diabetes-suppressive embodiment of Control Dendritic Cells which we term immunoregulatory dendritic cells iDC The IND covers the treatment of Control Dendritic Cells with phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulation molecules The Control DC and the oligonucleotide-treated dendritic cells iDC are the study cell products in this proposal
313 Leukapheresis Apparatus This will be performed with the Fenwal CS3000 Plus cell collector or equivalent using a large bore double lumen catheter as peripheral venous access with total processing of approximately 10-12 liters per session The device and its equivalents are FDA-approved for the procedures outlined herein to obtain purified leukocytes Staff experienced with leukapheresis contracted from the Central Blood Bank of Pittsburgh will perform these procedures
314 Psychological Measures The NEO-FFI is a 60 item paper and pencil questionnaire based on the five-factor theory of personality Neuroticism Extraversion Openness Agreeableness and Conscientiousness For this study we will examine the Neuroticism and Conscientiousness scales The Beck Depression Inventory 2nd edition BDI-2 and the Beck Anxiety Inventory BAI are each 21 item paper and pencil questionnaires which have been widely used in psychiatric and medical populations
32 Research Design and Methods 321 Settinglocation of the study Systemic physiologic and immunologic monitoring of patients prior to during treatment cycle and post-treatment will take place in the CTRC clinic of Montefiore University Hospital of UPMC Health System MUH-CTRC under the supervision of the co-investigator physicians of this study and the nurses of the CTRC Subjects will undergo leukapheresis in an outpatient setting at the MUH-CTRC or the University of Pittsburgh Cancer Center UPCI or the Central Blood Bank of Pittsburgh depending on the most convenient location for each patient receive the study dendritic cells in an outpatient setting at the MUH-CTRC and undergo the remaining tests and procedures at the MUH-CTRC Subjects will have approximately 16 visits at the locations described above each visit lasting about 2-4 hours depending on what procedures are being performed at that particular visit All results for each subject will be presented and discussed in an ongoing fashion at meetings held weekly at the UPCI outpatient clinic Subjects will be monitored during the dendritic cell administration cycle once every week following each dendritic cell administration for a period of nine weeks then once a month for the remainder of the year Refer to schematic cartoons in the Appendix Section 68
323 Autologous Control Dendritic Cell Vaccine Preparation Autologous DC will be generated from monocytes derived from leukapheresis product Leukapheresis will be performed at either of the following locations 1 MUH-CTRC 2 the UPCI Leukapheresis Unit or 3 the downtown location of the Central Blood Bank of Pittsburgh The product will be hand carried to the IMCPL located inside the Hillman Cancer Center in Shadyside by a nurse participating in the research study At the time of procurement immediately following leukapheresis the sample will be coded by the nurse using the same code assigned to the patient during enrollment At the IMCPL monocytes will be separated by elutriation in a closed ELUTRA system Monocytes will be cultured in the closed Aastrom Replicell System in the presence of IL-4 and GM-CSF to generate DC On day 6 of culture DC will be harvested and checked for viability and purity An aliquot of freshly-generated DC will be used for the control DC vaccine preparation while the remaining DC will be aliquoted into sterile cryovials and cryopreserved for preparation of subsequent vaccines We have calculated that to prepare a vaccine containing 1 x 107 viable control dendritic cells or iDC to be described below for each delivery One treatment defined as 1 x 107 dendritic cells injected at four intradermal sites anatomically-proximal to the pancreas we will need a total of 5 x 107 immature dendritic cells This is the minimal cell number estimate as additional aliquots of DC will be needed for testing prior to release of the vaccine for administration The cells will be tested for viability sterility bacterial aerobic and anaerobic cultures and Gram stain endotoxin level and mycoplasma as routinely performed by the IMCPL for cellular products used for human therapy at the UPCI For each vaccine the DC will be harvested counted adjusted into aliquots of 25 x 106 cellsmL in PBS with each aliquot and dispensed into a 1mL tuberculin syringe for future intradermal administration
324 Oligonucleotide-treated diabetes-suppressive iDC Vaccine Preparation The same procedures as for the generation of control DC will be used to generate the iDC preparation with the inclusion of the antisense oligonucleotides at the same time as when GM-CSF and IL-4 will be added to the DC progenitors The progenitors will be treated ex vivo with each of the antisense oligonucleotides to a final concentration of 33 μM according to SOP CPL-0170 Appended On day 6 of culture DC will be harvested and checked for viability and purity After extensive washing to remove the remaining oligonucleotides from the culture medium the iDC will be processed identically as above dispensed into administration aliquots and each aliquot will then be cryopreserved for future administrations
325 Control and iDC Vaccine safety The vaccine will be prepared and administered to established type 1 diabetic patients meeting the criteria outlined in Section 40-41 The dendritic cell vaccines will be produced in the IMCPL a cGMP facility which is in compliance with FDA recommendations for cellular products generated for patient therapy At all times the samples and the cell products will be identified by the same randomly-generated code assigned at the time of leukapheresis
326 Safety evaluation Initially 15 patients 18-35 years of age with established diabetes will be randomized to receive either the control dendritic cell vaccine 715 individuals or the iDC 815 individuals at the CHP GCRC Randomization will be carried out using a macro SUGI26 developed for the SAS statistics package SUGI26 is a modification of a baseline adaptive randomization procedure and permits for unequal allocation ratios among multiple treatment groups for categorical covariates
Following the establishment of the randomized patients into each treatment group a patient may receive either of the two dendritic cell embodiments control DC or iDC These patients will receive 1 x 107 dendritic cells intradermally four injections of 25 x 106 at four distinct sites anatomically-proximal to the pancreas at the times illustrated in SECTION 3211 and in the schematic cartoon refer to the Appendix Section 68 for a total of four vaccine administrations spaced every two weeks for a period of eight weeks Per administration we designate 4 unique intradermal injection sites inside the anterior abdominal wall perpendicularly-above the physical location of the stomach These four sites will be within a quadrant of 3-4 square-inches The cells will be delivered by a tuberculin syringe attached to a 27g-12 needle underneath a raised bleb of skin at each of the 4 individual injection sites If there is no grade 3 or 4 toxicity observed following the first vaccine cycle in the DC recipients successive vaccinations will be delivered as planned Dose-limiting toxicities will be defined as equal to or greater than grade 2 with the following exceptions chills malaise and fever are not considered dose limiting All grade 4 toxicities will be dose limiting with the exception of lymphocytopenia To protect patients against serious adverse effects of therapy the stopping rule will be observed as described in Section 332 below Following the leukapheresis procedure the patient will be monitored for normoglycemia and if necessary insulin will be administered as required to maintain normoglycemic levels Glycemia will also be monitored at the end of each DC administration procedure and insulin can be administered to restore normoglycemia if necessary
327 Dose-limiting toxicities
The following are considered to be dose limiting toxicities DLTs If these toxicities are felt to be related to autologous dendritic cell vaccine administration individual subjects will be immediately taken off study and no further injections will be given
Grade 2 or more bronchospasm
Grade 2 or more allergic reaction or generalized urticaria
Grade 2 or more autoimmune disease other than diabetes
Grade 2 injection site reaction due to vaccine or DTH testing
Grade 3 or 4 hematologic and non-hematologic toxicities
Grade 2 toxicities that do not resolve within 5 days following the dendritic cell vaccine administration
Dosing delays 4 weeks
Therapy may be discontinued for the following reasons
Intercurrent illness that prevents further administration of autologous dendritic cell vaccine including evidence of an infectious bacterialviral disease
Unacceptable adverse events
Patient decides to withdraw from the study or
General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator nurse or attending physicians
33 DATA COLLECTION AND STATISTICAL CONSIDERATIONS 331 General Considerations This will be a safety trial to evaluate the safety and feasibility of administering a diabetes-suppressive dendritic cell vaccine based on autologous dendritic cells treated ex vivo with phosphorothioate-modified antisense oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulatory molecules The vaccine will be given intradermally and each vaccine will contain 1 x 107 autologous dendritic cells A total of 4 vaccines will be delivered to each eligible subject A leukaphereses will be performed 14 days prior to the first vaccine to ensure sufficient numbers of DCs
The trial is designed to assure that the toxicity rate is acceptably low to warrant further study of the cell vaccine in efficacy trials
451 CLINICAL TRIAL MONITORING
4511 Reporting of Serious Adverse Events SAE
ADVERSE EVENTS In general all adverse events will be recorded and communicated to the safety officer the PI and to the DSMB within 24 hours of occurrence The safety officer will determine if the DSMB should meet under emergency session Any non-serious adverse event reports will be submitted to the IRB within 24 hours of the DSMB meeting The annual and final reports of the DSMB will also be submitted to the IRB and to the FDA within 48 hours of the meeting
Reporting of Serious Adverse Events SAE
All SAE will be recorded on the standard toxicity sheets and reported to the FDA the IRB the DSMB safety officer the Principal Investigator Dr Trucco andor Co-Investigators Drs Finegold Whiteside or Giannoukakis within 24 hours of occurrence All treatment-emergent serious adverse events and pre-existing medical conditions which unexpectedly worsen during therapy will be recorded and reported as described immediately above DSMB DSMB safety officer PI FDA IRB All serious adverse events or deaths which occur beyond thirty 30 days and which are reasonably likely to be related to control or iDC administration will be reported within 24 hours of the event to the safety officer the FDA and the full DSMB Any serious or adverse events or deaths which occur within thirty 30 days of the last control DC or iDC administration will be reported identically The safety officer will convene a full meeting of the DSMB within 24 hours of the occurrence of any SAE The DSMB report will then be submitted to the IRB and the FDA no later than 48 hours following the occurrence of the SAE
Serious is defined as described in 21 CFR 31232 a
Currently other than a humanized anti-CD3 antibody with considerable side effects there is no other means to reverse new-onset type 1 diabetes These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to possibly reverse it early on in the clinical process
We propose to ascertain the safety of autologous dendritic cells treated ex vivo with antisense oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulatory molecules we term these cells immunoregulatory dendritic cells iDC first in volunteers with established type 1 diabetes
Personality traits and emotional stability have been linked to treatment adherence in other medical populations eg Christensen et al 2002 Dew et al 2001 In that adherence to this protocol eg remaining in the study by this small sample will impact significantly on results and that the treatment itself may affect mood we will assess personality traits at baseline and monitor mood throughout the study period
22 Significance of the studies We do not anticipate any safety issues with this approach but we must be cautious at all levels given that this is immunomodulation therapy At the very least data will be obtained on whether the success we have observed with the iDC in NOD mice can be eventually adapted in other protocols aimed to restore normoglycemia or improve glycemic control along with increased prevalence of putative immunoregulatory T cells in recently-diagnosed humans
30 RESEARCH DESIGN AND METHODS
31 DrugDevice Information 311 Autologous Dendritic Cells Control Dendritic Cells These are cells derived from the leukapheresis product of each patient The leukapheresis product is processed inside an ElutraAastromTM cell elutriation system Refer to appended SOP CPL-0158 and CPL-0166 to obtain immature dendritic cells The final autologous product after these procedures is termed Control Dendritic Cells
312 Autologous Immunoregulatory Diabetes-Suppressive Dendritic Cells iDC We have submitted an IND application appended to the FDA to cover a diabetes-suppressive embodiment of Control Dendritic Cells which we term immunoregulatory dendritic cells iDC The IND covers the treatment of Control Dendritic Cells with phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulation molecules The Control DC and the oligonucleotide-treated dendritic cells iDC are the study cell products in this proposal
313 Leukapheresis Apparatus This will be performed with the Fenwal CS3000 Plus cell collector or equivalent using a large bore double lumen catheter as peripheral venous access with total processing of approximately 10-12 liters per session The device and its equivalents are FDA-approved for the procedures outlined herein to obtain purified leukocytes Staff experienced with leukapheresis contracted from the Central Blood Bank of Pittsburgh will perform these procedures
314 Psychological Measures The NEO-FFI is a 60 item paper and pencil questionnaire based on the five-factor theory of personality Neuroticism Extraversion Openness Agreeableness and Conscientiousness For this study we will examine the Neuroticism and Conscientiousness scales The Beck Depression Inventory 2nd edition BDI-2 and the Beck Anxiety Inventory BAI are each 21 item paper and pencil questionnaires which have been widely used in psychiatric and medical populations
32 Research Design and Methods 321 Settinglocation of the study Systemic physiologic and immunologic monitoring of patients prior to during treatment cycle and post-treatment will take place in the CTRC clinic of Montefiore University Hospital of UPMC Health System MUH-CTRC under the supervision of the co-investigator physicians of this study and the nurses of the CTRC Subjects will undergo leukapheresis in an outpatient setting at the MUH-CTRC or the University of Pittsburgh Cancer Center UPCI or the Central Blood Bank of Pittsburgh depending on the most convenient location for each patient receive the study dendritic cells in an outpatient setting at the MUH-CTRC and undergo the remaining tests and procedures at the MUH-CTRC Subjects will have approximately 16 visits at the locations described above each visit lasting about 2-4 hours depending on what procedures are being performed at that particular visit All results for each subject will be presented and discussed in an ongoing fashion at meetings held weekly at the UPCI outpatient clinic Subjects will be monitored during the dendritic cell administration cycle once every week following each dendritic cell administration for a period of nine weeks then once a month for the remainder of the year Refer to schematic cartoons in the Appendix Section 68
323 Autologous Control Dendritic Cell Vaccine Preparation Autologous DC will be generated from monocytes derived from leukapheresis product Leukapheresis will be performed at either of the following locations 1 MUH-CTRC 2 the UPCI Leukapheresis Unit or 3 the downtown location of the Central Blood Bank of Pittsburgh The product will be hand carried to the IMCPL located inside the Hillman Cancer Center in Shadyside by a nurse participating in the research study At the time of procurement immediately following leukapheresis the sample will be coded by the nurse using the same code assigned to the patient during enrollment At the IMCPL monocytes will be separated by elutriation in a closed ELUTRA system Monocytes will be cultured in the closed Aastrom Replicell System in the presence of IL-4 and GM-CSF to generate DC On day 6 of culture DC will be harvested and checked for viability and purity An aliquot of freshly-generated DC will be used for the control DC vaccine preparation while the remaining DC will be aliquoted into sterile cryovials and cryopreserved for preparation of subsequent vaccines We have calculated that to prepare a vaccine containing 1 x 107 viable control dendritic cells or iDC to be described below for each delivery One treatment defined as 1 x 107 dendritic cells injected at four intradermal sites anatomically-proximal to the pancreas we will need a total of 5 x 107 immature dendritic cells This is the minimal cell number estimate as additional aliquots of DC will be needed for testing prior to release of the vaccine for administration The cells will be tested for viability sterility bacterial aerobic and anaerobic cultures and Gram stain endotoxin level and mycoplasma as routinely performed by the IMCPL for cellular products used for human therapy at the UPCI For each vaccine the DC will be harvested counted adjusted into aliquots of 25 x 106 cellsmL in PBS with each aliquot and dispensed into a 1mL tuberculin syringe for future intradermal administration
324 Oligonucleotide-treated diabetes-suppressive iDC Vaccine Preparation The same procedures as for the generation of control DC will be used to generate the iDC preparation with the inclusion of the antisense oligonucleotides at the same time as when GM-CSF and IL-4 will be added to the DC progenitors The progenitors will be treated ex vivo with each of the antisense oligonucleotides to a final concentration of 33 μM according to SOP CPL-0170 Appended On day 6 of culture DC will be harvested and checked for viability and purity After extensive washing to remove the remaining oligonucleotides from the culture medium the iDC will be processed identically as above dispensed into administration aliquots and each aliquot will then be cryopreserved for future administrations
325 Control and iDC Vaccine safety The vaccine will be prepared and administered to established type 1 diabetic patients meeting the criteria outlined in Section 40-41 The dendritic cell vaccines will be produced in the IMCPL a cGMP facility which is in compliance with FDA recommendations for cellular products generated for patient therapy At all times the samples and the cell products will be identified by the same randomly-generated code assigned at the time of leukapheresis
326 Safety evaluation Initially 15 patients 18-35 years of age with established diabetes will be randomized to receive either the control dendritic cell vaccine 715 individuals or the iDC 815 individuals at the CHP GCRC Randomization will be carried out using a macro SUGI26 developed for the SAS statistics package SUGI26 is a modification of a baseline adaptive randomization procedure and permits for unequal allocation ratios among multiple treatment groups for categorical covariates
Following the establishment of the randomized patients into each treatment group a patient may receive either of the two dendritic cell embodiments control DC or iDC These patients will receive 1 x 107 dendritic cells intradermally four injections of 25 x 106 at four distinct sites anatomically-proximal to the pancreas at the times illustrated in SECTION 3211 and in the schematic cartoon refer to the Appendix Section 68 for a total of four vaccine administrations spaced every two weeks for a period of eight weeks Per administration we designate 4 unique intradermal injection sites inside the anterior abdominal wall perpendicularly-above the physical location of the stomach These four sites will be within a quadrant of 3-4 square-inches The cells will be delivered by a tuberculin syringe attached to a 27g-12 needle underneath a raised bleb of skin at each of the 4 individual injection sites If there is no grade 3 or 4 toxicity observed following the first vaccine cycle in the DC recipients successive vaccinations will be delivered as planned Dose-limiting toxicities will be defined as equal to or greater than grade 2 with the following exceptions chills malaise and fever are not considered dose limiting All grade 4 toxicities will be dose limiting with the exception of lymphocytopenia To protect patients against serious adverse effects of therapy the stopping rule will be observed as described in Section 332 below Following the leukapheresis procedure the patient will be monitored for normoglycemia and if necessary insulin will be administered as required to maintain normoglycemic levels Glycemia will also be monitored at the end of each DC administration procedure and insulin can be administered to restore normoglycemia if necessary
327 Dose-limiting toxicities
The following are considered to be dose limiting toxicities DLTs If these toxicities are felt to be related to autologous dendritic cell vaccine administration individual subjects will be immediately taken off study and no further injections will be given
Grade 2 or more bronchospasm
Grade 2 or more allergic reaction or generalized urticaria
Grade 2 or more autoimmune disease other than diabetes
Grade 2 injection site reaction due to vaccine or DTH testing
Grade 3 or 4 hematologic and non-hematologic toxicities
Grade 2 toxicities that do not resolve within 5 days following the dendritic cell vaccine administration
Dosing delays 4 weeks
Therapy may be discontinued for the following reasons
Intercurrent illness that prevents further administration of autologous dendritic cell vaccine including evidence of an infectious bacterialviral disease
Unacceptable adverse events
Patient decides to withdraw from the study or
General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator nurse or attending physicians
33 DATA COLLECTION AND STATISTICAL CONSIDERATIONS 331 General Considerations This will be a safety trial to evaluate the safety and feasibility of administering a diabetes-suppressive dendritic cell vaccine based on autologous dendritic cells treated ex vivo with phosphorothioate-modified antisense oligonucleotides targeting the primary transcripts of the CD40 CD80 and CD86 co-stimulatory molecules The vaccine will be given intradermally and each vaccine will contain 1 x 107 autologous dendritic cells A total of 4 vaccines will be delivered to each eligible subject A leukaphereses will be performed 14 days prior to the first vaccine to ensure sufficient numbers of DCs
The trial is designed to assure that the toxicity rate is acceptably low to warrant further study of the cell vaccine in efficacy trials
451 CLINICAL TRIAL MONITORING
4511 Reporting of Serious Adverse Events SAE
ADVERSE EVENTS In general all adverse events will be recorded and communicated to the safety officer the PI and to the DSMB within 24 hours of occurrence The safety officer will determine if the DSMB should meet under emergency session Any non-serious adverse event reports will be submitted to the IRB within 24 hours of the DSMB meeting The annual and final reports of the DSMB will also be submitted to the IRB and to the FDA within 48 hours of the meeting
Reporting of Serious Adverse Events SAE
All SAE will be recorded on the standard toxicity sheets and reported to the FDA the IRB the DSMB safety officer the Principal Investigator Dr Trucco andor Co-Investigators Drs Finegold Whiteside or Giannoukakis within 24 hours of occurrence All treatment-emergent serious adverse events and pre-existing medical conditions which unexpectedly worsen during therapy will be recorded and reported as described immediately above DSMB DSMB safety officer PI FDA IRB All serious adverse events or deaths which occur beyond thirty 30 days and which are reasonably likely to be related to control or iDC administration will be reported within 24 hours of the event to the safety officer the FDA and the full DSMB Any serious or adverse events or deaths which occur within thirty 30 days of the last control DC or iDC administration will be reported identically The safety officer will convene a full meeting of the DSMB within 24 hours of the occurrence of any SAE The DSMB report will then be submitted to the IRB and the FDA no later than 48 hours following the occurrence of the SAE
Serious is defined as described in 21 CFR 31232 a
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NIDDK R33 DK683044 | OTHER | NIH NIDDK | None |