Ignite Creation Date:
2024-05-06 @ 2:30 AM
Last Modification Date:
2024-10-26 @ 11:19 AM
Study NCT ID:
NCT02052492
Status:
COMPLETED
Last Update Posted:
2017-06-20
First Post:
2014-01-30
Brief Title:
Safety Study of EF-022 Modified Vitamin D Binding Protein Macrophage Activator in Subjects With Advanced Solid Tumors
Sponsor:
Efranat Ltd
Organization:
Efranat Ltd
Study Overview
Official Title:
A PHASE I OPEN LABEL DOSE-ESCALATION TRIAL EVALUATING THE SAFETY AND TOLERABILITY OF EF-022 MODIFIED VITAMIN D BINDING PROTEIN MACROPHAGE ACTIVATOR IN SUBJECTS WITH ADVANCED SOLID MALIGNANCIES
Status:
COMPLETED
Status Verified Date:
2017-06
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:
Activated macrophages present in excess during natural inflammatory responses bear the potential to kill and eradicate cancer cells Macrophage activation has been demonstrated to require the serum-borne vitamin D binding protein known as Gc protein as well as B and T lymphocytes However in various cancer patients the Gc protein is deglycosylated by serum α-N-acetyl galactosaminidase Nagalase secreted from cancer cells This deglycosylated Gc protein lacking the N-acetylgalactosamine monosaccharide cannot be converted to its form of Macrophage Activating Factor leading to immunosuppression rather than Macrophage activation against cancer cells
Efranat has developed cancer immunotherapy based on Macrophage Activating Factor produced from natural Gc protein extracted from FDA approved healthy human plasma
In this phase I study the treatment is given as Intramuscular once-weekly injection of EF-022 for two courses while each course is comprised of 4 injections
The investigational treatment is expected to enhance immune response thereby improve patients well being quality of life and disease control
Primary objectives
1 To determine the safety and tolerability of EF-022 and to define the maximal tolerated dose MTD for potential administration
2 To identify the Dose Limiting Toxicity DLT of EF-022
Secondary objectives
1 To determine the Recommended Phase 2 Dose RP2D based on MTD data immunological and pharmacodynamics markers
2 To explore preliminary efficacy of EF-022 in advanced solid tumors according to the Response Evaluation Criteria in the modified Solid Tumors RECIST 11 and blood levels of tumor-related markers known to reflect tumor burden
Exploratory objectives
1 To assess levels of immune-related factors in peripheral blood determined by FACS analysis reflecting induced immunological activities including but not limited to natural killer NK monocytes M1 and M2 and T cell subpopulations effector vs regulatory CD4 and CD8 cells B cells CD20 myeloid and dendritic cells etc
2 To assess the change in serum levels of protein biomarkers in the blood
3 To immunohistochemically assess and compare tumor derived tissue samples Pre and post treatment To analyze the infiltration of different population of cells into the tumor bed
Efranat has developed cancer immunotherapy based on Macrophage Activating Factor produced from natural Gc protein extracted from FDA approved healthy human plasma
In this phase I study the treatment is given as Intramuscular once-weekly injection of EF-022 for two courses while each course is comprised of 4 injections
The investigational treatment is expected to enhance immune response thereby improve patients well being quality of life and disease control
Primary objectives
1 To determine the safety and tolerability of EF-022 and to define the maximal tolerated dose MTD for potential administration
2 To identify the Dose Limiting Toxicity DLT of EF-022
Secondary objectives
1 To determine the Recommended Phase 2 Dose RP2D based on MTD data immunological and pharmacodynamics markers
2 To explore preliminary efficacy of EF-022 in advanced solid tumors according to the Response Evaluation Criteria in the modified Solid Tumors RECIST 11 and blood levels of tumor-related markers known to reflect tumor burden
Exploratory objectives
1 To assess levels of immune-related factors in peripheral blood determined by FACS analysis reflecting induced immunological activities including but not limited to natural killer NK monocytes M1 and M2 and T cell subpopulations effector vs regulatory CD4 and CD8 cells B cells CD20 myeloid and dendritic cells etc
2 To assess the change in serum levels of protein biomarkers in the blood
3 To immunohistochemically assess and compare tumor derived tissue samples Pre and post treatment To analyze the infiltration of different population of cells into the tumor bed
Detailed Description:
Part 1
Eligible subjects will be assigned successively in order of accrual to one of the three cohorts to receive intramuscular IM injections of EF-022 once weekly for two courses of treatment Each course will consist of 4 injections with one week intervals total 8 weeks of treatment
Dose escalation will only proceed in the absence of dose-limiting toxicity DLT during course 1 For this purpose each cohort will only begin its first course of EF-022 when the cohort preceding it has successfully completed its first 4-week treatment course without any signs of DLT During this first course should 13 patients experience DLT dose escalation for the next cohort will not be authorized the next cohort will receive the same dose as the one preceding it If 2 patients or more of all patients treated with a given dose develop DLT dose escalation will be halted and no more patients will be treated at the DLT dose The value of MTD will be defined as the EF-022 dose below the dose at which DLT was seen for at least 2 subjects Upon determination of the MTD an additional cohort will be opened confirmatory cohort and treated with two courses of that dose
Part 2
During the expanded cohort 24 Patients will be allocated to receive either 100ng 500ng or 1000ng weekly treatment as detailed below The first 18 patients will be assigned to alternating doses of either 100ng or 500ng in a sequential manner each patient will be assigned to a single dose with the caveat that given indications should be assigned equally as much as possible between these two doses
Interim analysis will be performed once the 12th patient reaches Day 57 and the CT results as well as PD analysis are available for at least 12 patients while at least 18 patients have begun study treatment A decision regarding adding a 1000ng dose cohort vs continuing with the 100ng and 500ng doses will be based on a discussion of the interim analysis results
Each patient will receive 2 courses of treatment ie weekly injections for a total period of 8 weeks followed by a follow-up period of up to 12 months from the start of treatment Day 1
Continuation of treatment after the second course will be at the discretion of the investigator Patients who will continue extended treatment post course 2 will keep the weekly injection dosage mode and continue therapy until disease progression development of unacceptable toxicities non-compliance inter-current illness that prevents treatment continuation withdrawal of consent or change in subject condition that renders the subject unacceptable for further treatment
All study patients who completed at least two courses of treatment will be followed up until 12 months from day 1 of treatment
Eligible subjects will be assigned successively in order of accrual to one of the three cohorts to receive intramuscular IM injections of EF-022 once weekly for two courses of treatment Each course will consist of 4 injections with one week intervals total 8 weeks of treatment
Dose escalation will only proceed in the absence of dose-limiting toxicity DLT during course 1 For this purpose each cohort will only begin its first course of EF-022 when the cohort preceding it has successfully completed its first 4-week treatment course without any signs of DLT During this first course should 13 patients experience DLT dose escalation for the next cohort will not be authorized the next cohort will receive the same dose as the one preceding it If 2 patients or more of all patients treated with a given dose develop DLT dose escalation will be halted and no more patients will be treated at the DLT dose The value of MTD will be defined as the EF-022 dose below the dose at which DLT was seen for at least 2 subjects Upon determination of the MTD an additional cohort will be opened confirmatory cohort and treated with two courses of that dose
Part 2
During the expanded cohort 24 Patients will be allocated to receive either 100ng 500ng or 1000ng weekly treatment as detailed below The first 18 patients will be assigned to alternating doses of either 100ng or 500ng in a sequential manner each patient will be assigned to a single dose with the caveat that given indications should be assigned equally as much as possible between these two doses
Interim analysis will be performed once the 12th patient reaches Day 57 and the CT results as well as PD analysis are available for at least 12 patients while at least 18 patients have begun study treatment A decision regarding adding a 1000ng dose cohort vs continuing with the 100ng and 500ng doses will be based on a discussion of the interim analysis results
Each patient will receive 2 courses of treatment ie weekly injections for a total period of 8 weeks followed by a follow-up period of up to 12 months from the start of treatment Day 1
Continuation of treatment after the second course will be at the discretion of the investigator Patients who will continue extended treatment post course 2 will keep the weekly injection dosage mode and continue therapy until disease progression development of unacceptable toxicities non-compliance inter-current illness that prevents treatment continuation withdrawal of consent or change in subject condition that renders the subject unacceptable for further treatment
All study patients who completed at least two courses of treatment will be followed up until 12 months from day 1 of treatment
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