临床试验雷达

Participant has known allergy, hypersensitivity or moderate to severe allergic reaction including anaphylaxis to natural or recombinant antibodies, biologic treatments, passive vaccines, pork, or any other component of the study drug formulation (including biologic medications).

Participant has a known allergy or hypersensitivity to any of the protocol-required concomitant medications.

Participant has been an active participant in a therapeutic drug, invasive medical device, or vaccine clinical trial within 12 weeks before Screening Visit (SV)2.

Participant has received teplizumab or any investigational immunomodulatory anti-CD3 treatment within any timeframe prior to screening.

Participant has a significant uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, neurologic, haematologic, rheumatologic, oncologic, psychiatric, or immune deficiency that may interfere with the participant's safely participating in the study or with interpretation of the safety and/or efficacy profile of investigational medicinal product (IMP). For any disorders, a participant with a stable, well-controlled condition that is not felt to interfere with study participation may be enrolled.

Participant has any autoimmune disease other than T1D (e.g., latent autoimmune diabetes in adults, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythaematous) that is currently managed with systemic immunotherapy, with the exception of clinically stable thyroid or celiac disease.

Participant 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.

Participant has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV)-1 or 2, hepatitis B virus (HBV), or hepatitis C virus (HCV) antibodies.

Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and/or TB testing. Note: Blood testing (e.g., QuantiFERON® TB Gold test) is strongly preferred; if not available, any local approved TB test is allowed.

Serious systemic viral, bacterial, or fungal infection (e.g., pneumonia, pyelonephritis), infection requiring hospitalization or IV anti-infective treatments or significant acute or chronic viral (including history of recurrent or active herpes zoster, acute or active cytomegalovirus \[CMV\], Epstein-Barr Virus \[EBV\] as determined at screening), bacterial, or fungal infection (e.g., osteomyelitis) 30 days before and during screening. Note: Participants with confirmed active EBV or CMV infection based on polymerase chain reaction (PCR) test can be retested; asymptomatic participants with the most recent PCR-negative test are eligible for participation. Participants with an active mild infection at Screening may be enrolled once the symptoms have resolved and all I/E are met. Participants who have an active infection and/or fever ≥38.0°C (100.4°F) within the 48 hours prior to dose administration should not be dosed.

Participant has a diagnosis of significant liver disease or at screening ALT and/or AST >2× or total bilirubin of >1.5× of the age- and sex-specific upper limit of normal (ULN) according to the central laboratory and confirmed by repeated tests. Liver function tests can be repeated during screening and if normalised, participant maybe eligible for randomization. Note: Participants with Gilbert's syndrome are allowed to enrol if only total and/or indirect bilirubin are elevated above ULN while ALT, AST, and alkaline phosphatase (ALP) are within the normal laboratory ranges.

An individual has any of the following haematologic parameters, confirmed by repeat tests, during Screening:

• Lymphocyte count: <1000/μL
• Neutrophil count: <1500/μL
• Platelet count: <100 000 platelets/μL
• Haemoglobin: <10 g/dL Note: Specific haematologic, oncologic or other systemic conditions that might otherwise result in exclusion and/or is heretofore unrecognised should be considered in individuals who have one or more blood cell counts below or above the normal ranges.

Current or prior (within 5× half-lives before SV2) treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including systemic glucocorticoids, verapamil, baricitinib, and others. Note: Inhaled and topical corticosteroids are allowed. Short courses, i.e., approximately 2 weeks or less, of systemic corticosteroids for transient conditions are allowed.

Current or prior (within 5× half-lives before SV2) use of drugs other than insulin to treat hyperglycaemia (e.g., metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, glucagon-like peptide 1 agonists \[glucagon-like peptide-1\], dipeptidyl peptidase-4 \[DPP-IV\] inhibitors, or amylin).

Current or prior (within 5× half-lives before SV2) use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin).

Current or planned highly restrictive dietary regimen(s) that would interfere with participant well-being or impact to investigational drug.

Recent or planned vaccinations as follows:

• Live vaccines (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox): Within the 30 days before dosing or within 60 days following dosing; or planned/required within 30 days prior to or 60 days following Day 1 of TP2.
• Recombinant, inactivated or otherwise "non-live" vaccines: Within the 30 days before dosing or within 60 days following dosing; or planned/required within 30 days prior to or 60 days following Day 1 of TP2.

Female is lactating and/or plans to lactate with the intent to provide her own breast milk to a baby at any point during the study.

An individual who has a history of alcohol, drug, or chemical abuse within 12 months prior to study screening (positive tetrahydrocannabinol is allowed) Note: Abuse is defined according to local, regional and/or country specific guidance. Participants who are tested positive for illicit substances but have a prescription medication to manage their concomitant conditions such as attention-deficit/hyperactivity disorder (ADHD) or others are allowed to participate in the study.

An individual who has a medical, psychological or social condition that, in the opinion of the Investigator, would interfere with safe and proper completion of the trial.

An individual who is an employee of the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site.