A phase 3 clinical study of teplizumab for treatment of children and adolescents with newly diagnosed type 1 diabetes
- Conditions
- Type 1 Diabetes (T1D)MedDRA version: 20.0Level: LLTClassification code 10012594Term: DiabetesSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004926-26-FI
- Lead Sponsor
- Provention Bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 300
1. Participant is male or female.
2. Participant is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration.
3. Participant has received a diagnosis of T1D according to ADA criteria
4. Participant is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis according to the ADA criteria.
5. Participant has a peak stimulated C-peptide of =0.2 pmol/mL from a 2-hour mixed meal tolerance test (2h MMTT) at screening. (Note: This screening 2h MMTT must occur only after 6 days following diagnosis to allow for reduction of metabolic instability.)
6. Participant has a positive result on testing for at least one of the following T1D-related autoantibodies before randomization:
• Glutamic acid decarboxylase 65 (GAD65) autoantibodies
• Islet antigen 2 (IA-2) autoantibodies
• Zinc transporter 8 (ZnT8) autoantibodies
• Islet cell cytoplasmic autoantibodies (ICA) or
• Insulin autoantibodies (if testing obtained within the first 14 days of insulin treatment)
7. Female participants of childbearing potential must have a negative result on highly sensitive serum (ß human chorionic gonadotropin [ß-HCG]) at screening.
8. Participants who have reached puberty must agree to adhere to the following contraceptive requirements (Note: In countries with legislation for the age of sexual activity, the participant must comply with the local age limit regarding the use of contraception):
• Females with childbearing potential (defined as premenopausal females who are capable of becoming pregnant, ie, having reached menarche or having reached Tanner stage 3 breast development even without menarche) or who gain childbearing potential during the study must practice abstinence or use 2 forms of contraception (including oral, transdermal, injectable, or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner, or a sterile sexual partner) continuously from 30 days before the first dose of study drug through the end of the study.
• Males who have reached puberty (ie, spermatogenesis) with partners of childbearing potential must use barrier contraception in addition to having their partners use another method of contraception from 1 week before each study agent dose through 120 days (a complete spermatogenesis cycle) after receiving the last dose in each treatment course.
9. Prior to receiving study drug, participant must be up to date with and/or agree to receive routine age-appropriate immunizations and comply with the guidelines for immunosuppressed individuals and those with chronic disease (diabetes mellitus) according to current local, regional and/or country-specific guidelines.
10. Participant agrees not to receive other forms of experimental treatment during the study, particularly agents that may be immune modulatory in nature and/or stimulate pancreatic ß cell regeneration or insulin secretion
11. Participant and/or appropriate legal guardian must sign an informed consent form (ICF) and/or assent according to local, regional and/or country-specific guidance for study participation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) no
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
1. Known allergies, severe reaction, intolerance, hypersensitivity, or anaphylaxis to human, humanized, or murine monoclonal antibodies, teplizumab or any of its components or its excipients.
2. An active participant in a therapeutic drug, invasive medical device, or vaccine clinical trial within 12 weeks before the first dose of drug or has received an investigational treatment with the potential for T1D disease modification.
3. Significant renal, cardiac, vascular, pulmonary, gastrointestinal, neurologic, hematologic, rheumatologic, oncologic, psychiatric disease, or immune deficiency.
4. Any autoimmune disease other than T1D (eg, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematous), with the exception of clinically stable thyroid or celiac disease.
5. An active infection and/or fever =38.5°C (101.3°F) within the 48 hours prior to randomization, is prone to infections, or has chronic, recurrent or opportunistic infectious disease, including but not limited to renal, respiratory or skin infections, Pneumocystis carinii, aspergillosis, latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis.
6. A history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
7. Any of the following in regards to tuberculosis (TB): history of latent or active TB, signs and/or symptoms of TB, recent close contact with a person with known or suspected active TB, history of a chest X-ray consistent with active TB or old, inactive TB, hstory of a positive purified protein derivative skin test result (>10 mm induration) or at screening is positive or repeatedly indeterminate with an approved interferon-gamma release assay (IGRA; eg, QuantiFERON-TB test); recent (within 3 months) chest X-ray or one conducted at screening read by a qualified radiologist consistent with current, active TB or old, inactive TB
8. At screening, a clinically active infection with EBV, including but not limited to infectious mononucleosis, or an EBV viral load =10,000 copies per mL or per 10^6 lymphocytes obtained at screening.
9. At screening, a clinically active infection with CMV or a CMV viral load 10,000 copies per mL or per 10^6 lymphocytes.
10. A diagnosis of significant liver disease or at screening alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2X or total bilirubin (TBili) of >1.5X of the age- and sex-specific upper limit of normal (ULN) according to the central laboratory. (Note: Participants with Gilbert's syndrome may be allowed to enroll upon approval by the Medical Monitor.)
11. Any of the following hematologic parameters:
• Lymphocyte count: <1000/µL
• Neutrophil count: <1000/µL
• Platelet count: <100,000 platelets/µL
• Hemoglobin: <10 g/dL
12. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including high-dose inhaled, extensive topical, or systemic glucocorticoids.
13. Current or prior use of drugs other than insulin to treat hyperglycemia.
14. Current or prior use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
15. Current or planned highly restrictive dietary regimen(s) intended for T1D management, such as very-low or ultra-low carboh
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine whether two courses of teplizumab administered 6 months apart slow the loss of ß cells and preserve ß cell function over 18 months (78 weeks) in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.;Secondary Objective: • To evaluate participant improvements in key clinical parameters of diabetes management, including insulin use, glycemic control (including hemoglobin A1c [HbA1c] and time in glycemic target range [TIR], and clinically important hypoglycemic episodes<br>• To determine the safety and tolerability of two courses of teplizumab, administered intravenously (IV) 6 months apart<br>• To evaluate the pharmacokinetics (PK) and immunogenicity of two courses of IV teplizumab;Primary end point(s): The area under the time-concentration curve (AUC) of C-peptide after a 4-hour (4h) mixed meal tolerance test (MMTT), a measure of endogenous insulin production and ß cell function, at Week 78.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Exogenous insulin use: defined as a daily average in units per kilogram per day (U/kg/d), at Week 78<br>• HbA1c levels: expressed in % and mmol/mol, at Week 78<br>• TIR: expressed as a daily average of the percentage of time in a 24 hour-day a participant’s BG is >70 but =180 mg/dL (>3.9 to =10.0 mmol/L) assessed using continuous glucose monitoring (CGM), at Week 78<br>• Clinically important hypoglycemic episodes: defined as the total number of episodes of a BG reading of <54 mg/dL (3.0 mmol/L) and/or episodes of severe cognitive impairment requiring external assistance for recovery, from randomization through Week 78;Timepoint(s) of evaluation of this end point: Week 78