Chronic Kidney Disease, End Stage Renal Disease
Conditions
Brief summary
The objectives of this study are to assess safety and to evaluate the biologic activity of TARGTEPO treatment.
Detailed description
This is a Phase I-II, open-label study. Each patient will receive targeted dose of EPO delivered via TARGTEPO. The targeted doses will be determined according to 3 cohorts as follows: Group A (18-25 IU/Kg/day), Group B (35-45 IU/Kg/day), Group C (55-65 IU/Kg/day). The objective is to evaluate safety and biologic activity of TARGTEPO treatment when maintaining Hb levels within the target range of 9-12 g/dl. Biological activity assessments will include duration of TARGTEPO secretion as measured by serum EPO levels above baseline
Interventions
BIOLOGICALMDGN201 TARGTEPO
Erythropoietin secreted by TARGTEPO transduced with MDGN201
Sponsors
Medgenics Medical Israel Ltd.
Aevi Genomic Medicine, LLC, a Cerecor company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. For ESRD patients: Subject diagnosed with Anemia due to Chronic Renal Failure CKD stage 5 on hemodialysis treatment for at least 6 months. Average Hb during last month between 9 to 12g/dL. 2. Kt/V \>1 3. INR not higher than 1.2 4. Serum albumin \>3.5 5. Subjects with adequate iron stores (transferrin saturation \> 20.0% and/or ferritin \>100 ng/ml).
Exclusion criteria
1. Uncontrolled hypertension (defined as diastolic blood pressure \> 110 mmHg or systolic blood pressure \> 180 mmHg during screening). 2. Subjects who receive oral anti-coagulation treatment (e.g. warfarin) 3. Subjects who receive Acetyl Salicylic Acid (ASA) above 325 mg/day or patients who receive ASA treatment between 100mg/d and 325 mg/d who cannot discontinue it for 1 week prior to each EPODURE procedure 4. Patients currently receiving injections of long-acting Erythropoiesis Stimulating Agents (ESA) (e.g. Aranesp, Mircera), a patient on long acting ESA can be switched to a short acting preparation (e.g Eprex) and enroll in the study after meeting the inclusion criteria and not meeting any other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total EPO Secretion | up to 52 weeks | — |
| Percent (%) of Hb Measurements After Implantation Within 9-11 g/dL | 52 weeks | — |
| Percent (%) of Hb Measurements After Implantation Within 9-12 g/dL | 52 weeks | Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d. |
Countries
Israel
Participant flow
Pre-assignment details
A total of 14 patients signed the Informed Consent Form and underwent the study screening procedures. Of these 14 patients, a total of 11 patients were enrolled into Study MG-EP-RF-02. These 11 patients are included in the ITT cohort. One patient (Group B) had an SAE prior to study procedures and became no longer eligible.
Participants by arm
| Arm | Count |
|---|---|
| Group A 18-25 IU/Kg/day | 6 |
| Group B 35-45 IU/Kg/day | 5 |
| Group C 55-65 IU/Kg/day | 0 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | No longer meets inclusion criteria | 0 | 1 | 0 |
| Overall Study | Permanent need for exogenous EPO Tx | 2 | 0 | 0 |
| Overall Study | Permanent need for exogenous ESA Tx | 3 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 0 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 1 / 4 | 0 / 0 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 0 / 0 |
| serious Total, serious adverse events | 2 / 6 | 4 / 4 | 0 / 0 |
Outcome results
Primary
Percent (%) of Hb Measurements After Implantation Within 9-11 g/dL
Time frame: 52 weeks
Population: Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d. One subject enrolled was discontinued prior to study procedures and became no longer eligible.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Subjects Enrolled | Percent (%) of Hb Measurements After Implantation Within 9-11 g/dL | 49.2 percent |
Primary
Percent (%) of Hb Measurements After Implantation Within 9-12 g/dL
Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d.
Time frame: 52 weeks
Population: Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d. One subject enrolled was discontinued prior to study procedures and became no longer eligible.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Subjects Enrolled | Percent (%) of Hb Measurements After Implantation Within 9-12 g/dL | 75.3 percent |
Primary
Total EPO Secretion
Time frame: up to 52 weeks
Population: Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d. One subject enrolled was discontinued prior to study procedures and became no longer eligible.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Subjects Enrolled | Total EPO Secretion | 24.1 U/Kg/d |