A study to evaluate the Safety, Tolerability, Pharmacodynamics, and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase (EE-TP) in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
- Conditions
- Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)MedDRA version: 20.1 Level: PT Classification code 10058799 Term: Mitochondrial encephalomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2018-003000-39-GB
- Lead Sponsor
- St George’s University of London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 20
1. Patients must be male or female, of any race, aged 18 years or
older at Screening.
•Having reviewed the benefit-risk profile and with appropriate approval from ECs and/or regulatory agencies, the age range may be extended to include patients:
- aged 16 years or older after at least 12 patient-months of exposure in patients aged 18 years or over.
- aged 12 years or older after at least 12 patient-months of exposure in patients aged <18 years at the time of enrolment.
2. Patients must be diagnosed with MNGIE by demonstrating ALL of the following:
•<18% normal TP activity in the buffy coat;
• >3 µmol/L plasma thymidine;
• >5 µmol/L plasma deoxyuridine;
• confirmation of the presence of a pathogenic mutation in TYMP gene by sequencing.
3. Patients must be able to undergo study procedures. Patients must agree to either remain completely true abstinent (because of the patient’s lifestyle choice; the patient should not become abstinent just for the purpose of study participation) or to use two effective contraceptive methods from Screening until completion of the Follow-up visit:
•Male patients with partners of childbearing potential must use a male barrier method of contraception (i.e., male condom with spermicide) in addition to a second method of acceptable contraception used by their female partners (refer to Section 4.6.6).
• Female patients of childbearing potential must be willing to use a highly effective method of birth control (i.e., contraceptive measures with a failure rate of <1% per year):
- IUD (e.g., Mirena) which was implanted at least 2 months prior to Screening. Steel or copper IUDs are not acceptable.
- Established use of oral, implanted, transdermal, or hormonal method of contraception associated with inhibition of ovulation.
- Male sterilisation, with verbal confirmation of surgical success (for female patients on the study, the vasectomised male partner should be the sole partner for that patient).
- Bilateral tubal ligation.
5. Patients must be willing to sign and date the written ICF after the benefits and risks of taking part in this study have been explained to them, and to comply with the study restrictions.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Patients who have received a successful liver or bone marrow transplant.
2. Patients with a known history of human immunodeficiency virus (HIV), hepatitis B infection, or an active hepatitis C infection.
3. Patients who are severely disabled (e.g., patient bed-bound, incontinent, and unable to carry out any daily activities), or with a life expectancy of less than 12 months at Screening, based on the Investigator’s judgment.
4. Female patients who are:
•pregnant, planning a pregnancy, or are unwilling to use contraception
•breastfeeding or lactating.
5. Patients who have donated blood in the 90 days prior to Screening.
6. Patients with a confirmed RBC count of <3.0 × 109 per mL.
7. Patients who have a significant history of alcoholism or drug/chemical abuse within 1 year prior to Screening, as determined by the Investigator.
8. Patients who have an abnormality in heart rate, blood pressure, or body temperature at Screening that, in the opinion of the Investigator, increases the risk of participating in the study.
9. Patients who have an abnormality in the 12-lead electrocardiogram (ECG) at Screening that, in the opinion of the Investigator, increases the risk of participating in the study.
10. Patients who have, or have a history of, any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological, or other major disorder (except for MNGIE, or disorders associated with MNGIE that, in the Investigator’s opinion, do not constitute a risk when taking study medication and would not interfere with the study objectives) as determined by the Investigator.
11. Patients with any current malignancy, or a history of malignancy within 5 years prior to Screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
12. Patients who are currently enrolled in, or are planning to participate in, or discontinued within the last 30 days from a clinical study involving an investigational medicinal product (IMP) or concurrently enrolled in medical research judged not to be scientifically or medically compatible with EE-TP.
13. Patients with any medical condition, which in the opinion of the Investigator, would make the patient unsuitable for enrolment or could interfere with the patient’s participation in, or completion of, the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: To determine the safety, tolerability, pharmacodynamics (PD), and efficacy (as measured by weight stabilisation) of multiple doses of EE-TP manufactured using the red cell loader (RCL) in patients with MNGIE.<br> ;<br> Secondary Objective: • To assess the immunogenicity of EE-TP after multiple dose<br> administrations.<br> • To assess changes in clinical assessments.<br> • To assess the PD effect of EE-TP on clinical assessments.<br> ;Primary end point(s): •Mean absolute change from baseline in BMI from baseline at 24 months;Timepoint(s) of evaluation of this end point: Please refer to Schedule of Assessments in the protocol.
- Secondary Outcome Measures
Name Time Method