Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) MedDRA version: 20.1 Level: PT Classification code 10058799 Term: Mitochondrial encephalomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Erythrocyte Encapsulated Thymidine Phosphorylase
Product Code: EE-TP
Pharmaceutical Form: Infusion
INN or Proposed INN: TP
Sponsors
St George’s University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ; Secondary Objective: • To assess the immunogenicity of EE-TP after multiple dose administrations. • To assess changes in clinical assessments. • To assess the PD effect of EE-TP on clinical assessments. ;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
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Please refer to Schedule of Assessments in the protocol.; Secondary end point(s): •Mean absolute change from baseline BMI at 3, 6, 9, 12, 15, 18, and 21 months •Change from baseline in the proportion of patients who require TPN or have deceased at 3, 6, 9, 12, 15, 18, 21, and 24 months •Mean absolute change from baseline handgrip strength measured using handgrip dynamometry (for assessment of distal muscle weakness) employed according to the Southampton protocol for adult grip strength at 6, 12, 18, and 24 months •Mean absolute change from baseline disability measured using the I-RODS at 6, 12, 18, and 24 months •Mean absolute change from baseline ambulatory function measured using the timed 10-metre walk test at 6, 12, 18, and 24 months •Mean absolute change from baseline quality of life measured using EuroQol-5D and CGI-I at 6, 12, 18, and 24 months •Mean absolute change from baseline of gastrointestinal (GI) symptoms measured using PROMIS® short form scales (GI belly pain, GI diarrhoea, GI disrupted swallowing, GI gas and bloating, GI gastroesophageal reflux, and GI nausea and vomiting) at 6, 12, 18, and 24 months •PGIC at 6, 12, 18, and 24 months, relative to baseline •Changes relative to baseline in distal sensory impairment and deep tendon reflexes using neurological exam tests recorded in a standardised fashion •Improvement of the most disabling symptom for each patient (assessed using the VAS) | — |
Countries
France, Germany, Israel, Italy, Spain, United Kingdom
Contacts
Public ContactResearch Governance and Delivery
St George’s University of London
Outcome results
None listed