Type I Diabetes Mellitus MedDRA version: 8.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus
Conditions
Interventions
Product Name: TRX4 (Monoclonal anti-CD3 Antibody)
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: TRX4 (monoclonal anti-CD3 antibody)
Concentration unit: mg/ml milligr
Sponsors
TolerRx, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects able to give informed consent 2) Men or women of any race, between 18 and 60 years old (inclusive), in good general health 3) Confirmed diagnosis of Type 1 Diabetes Mellitus, insulin-requiring, on a relatively stable insulin regimen for one month prior to initiating TRX4 dosing, with good metabolic control (HbA1c less than 8.5 %) 4) Less than 10 % weight loss due to Diabetes in the past six months 5) Positive for at least one Type 1 Diabetes Mellitus autoantibody, i.e. anti-GAD (glutamic acid decarboxylase), IA-2, or insulin autoantibody 6) Willingness to remain in the clinic for the inpatient portion of the study 7) Prescription medications must be stable for at least four weeks before the first dose of study drug 8) Female subjects must not be pregnant or lactating and either be surgically sterile, postmenopausal for at least one year, or using an acceptable method of contraception defined as oral, implanted, or transdermal contraceptive, plus one of the following barrier methods: diaphragm with spermicidal cream/jelly or use of a condom by sexual partner 9) Screen body-mass-index of less than 34 10) Negative PPD skin test at screen (may be reactive, but not positive) 11) No clinically significant abnormal laboratory values within one week of the first TRX4-dose 12) Negative Hepatitis-C antibody, Hepatitis-B surface antigen, Hepatitis-B core antibody 13) Negative HIV antibody and no risk factors for HIV infection 14) Seropositive for Epstein-Barr-Virus (EBV) with quantitative polymerase chain reaction of less than 10000 copies of EBV DNA / 1000000 lymphocytes 15) CD4+ lymphocyte counts must be within normal limit within 35 days prior to the first dose of TRX4. 16) Negative syphilis test. 17) Negative qualtitative urine drug or alcohol test at screen. 18) Other than T1DM, all organ systems must be free of significant disease and the subject cannot have undergone recent clinically significant surgery. 20) The investigator must judge all pre-admission vital signs, physical examination, laboratory, or any safety variables to be within normal limits or clinically insignificant. 21) Negative / below detectable limit serum rheumatoid factor (RF). Are the trial subjects under 18? no 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Subjects with a current or prior malignancy, other than non-melanoma skin cancer (subjects with more than 5 occurrences of non-melanoma skin cancer and the last occurrence within 3 months of study entry). 2) Subjects that have received a vaccine within 30 days before TRX4 dosing, OR anticipate requiring a vaccine within 14 days after the last dose of TRX4. 3) Subjects considering or have scheduled any surgeries during the Core Study. 4) Subject with any significant mental or physical illness within a one year period prior to the first dose, including a history of alcohol and/or drug abuse. 5) Subjects having donated plasma or blood within 30 days prior to the first dose of TRX4. 6) Subjects having used any investigational drugs within three months prior to the first dose of TRX4 or within the core study period. 7) Subjects with a history of anaphylactic reactions. 8) Subjects having experienced a significant systemic infection within three months before the first dose of TRX4. 9) Subjects who may, based on medical history, require treatment with systemic corticosteroids during the study. 10) Subjects thought to have an allergy or sensitivity to TRX4 or excipients based upon known allergies to compounds of a similar class, or which, in the opinion of the principal investigator, suggests an increased potential for an adverse hypersensitivity to TRX4. 11) Subjects having received any other anti-CD3 Mab at any time in the past (e.g., OKT3; ChAglyCD3; OKT3 ala-ala). 12) Subjects having undergone splenectomy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) Define a maximum dose level at which there is negligible cytokine release, especially for the first dose of each multiple dose regimen. 2) Evalute the effect of TRX4 on standard safety parameters (CBC, WBC differential, hepatic function tests and other serum chemistries, ECG, etc. ) and on EBV reactivation.;Secondary Objective: 1) Confirm that there is progressively less cytokine release with each dose of the four-dose regimens. 2) Determine the pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of TRX4 in Type 1 Diabetes Mellitus (T1 DM). 3) Compare safety, PK/PD, and cytokine release data with similar data collected in previous studies in psoriasis and new onset Type 1 Diabetes Mellitus (NOT1DM). 4) Characterize whether TRX4 is immunogenic. 5) Evaluate the effect of TRX4 on long-term safety (months 6-48) after the Core Study (3 months) is completed. 6) Identify an appropriate prophylaxis regimen to minimize cytokine release-related symptoms.;Primary end point(s): 1) Pharmacokinetics: Blood samples will be collected prior to, during, and at specified times following dosing of study medication for determination of free TRX4 concentrations in serum. Using noncompartmental analyses, single dose parameters including Cinf, Cmax, tmax, AUC(0-z), AUC(0-8), AUC(0-24h), CL, lambda-z, t1/2, and Vd will be calculated. In addition, pharmacokinetic linearity will be examined. 2) Pharmacodynamics: Saturation and modulation of CD3 on the surface of circulating T cells, utilizing mean channel fluorescence as determined by flow cytometry, will be presented graphically by dose and time. Individual lymphocyte subset values will be presented graphically by dose and time based on two types of cell quantification, percent of baseline for each subset (as a percent) and percent of baseline for absolute cell count. Exploratory endpoints and other pharmacodynamic assessments will include: 1) C-reactive protein, 2) C-peptide levels, 3) exogenous insulin | — |
Countries
Germany, United Kingdom
Outcome results
None listed