| Eligibility |
Inclusion Criteria:
1. Written informed consent, and if needed assent from the child on the trial, must be
obtained before any assessment is performed.
2. Males and females aged between 6 and 21 years (inclusive, and enrolled in stages) at
screening.
3. Body weight range from 20 to 125 kg (inclusive).
4. Evidence of one or more type 1 diabetes autoantibody(ies) against: glutamic acid
decarboxylase (anti-GAD), protein tyrosine, phosphatase-like protein (anti-IA-2); zinc
transporter 8 (anti-ZnT8); islet cell (cytoplasmic) (anti-ICA) at screening or
baseline in the central laboratory OR historical clinical record of one or more of the
T1DM diabetes autoantibodies. As part of the historical record insulin autoantibodies
(IAA) may have been used as part of the autoantibody panel but the blood sample must
have been obtained prior to or within one week of starting exogenous insulin
treatment.
5. Able to receive first dose of study drug within 56 days of diagnosis of T1DM (which
may be extended to within 100 days of diagnosis in the event a screening assessment
needs to be confirmed or vaccine administered).
6. Peak stimulated C-peptide levels =0.2 nmol/L (0.6 ng/mL) following standard liquid
mixed meal tolerance test (MMTT), to be conducted when the subject is metabolically
stable, at least 2 weeks from diagnosis and within 56 days prior to randomization (or
within 100 days of diagnosis in the event a screening assessment needs to be confirmed
or vaccine is required).
7. Study participants are to complete all recommended immunizations with live, attenuated
vaccine at least eight weeks prior and killed, inactivated vaccine at least two weeks
prior to first dose with study drug and in accordance with local immunization
guidelines. In the event a subject has not had all vaccinations recommended according
to local guidance, the screening period may be extended beyond 56 days to allow these
vaccinations to be administered, but first dose of study drug must be administered
within 100 days of diagnosis of T1DM.
8. Must be willing to comply with the standard of care for diabetes management.
9. A negative pregnancy test at screening is required for all sexually mature female
subjects prior to participation in the study.
10. Subject and/or guardian must be able to communicate well with the investigator, to
understand and comply with the requirements of the study.
Exclusion Criteria:
1. Diabetes forms other than auto immune type 1 such as maturity-onset diabetes of the
young (MODY), latent autoimmune diabetes of the adult (LADA), acquired diabetes
(secondary to medications or surgery), type 2 diabetes by judgement of the
investigator.
2. Diabetic ketoacidosis within 2 weeks of the baseline MMTT test.
3. Polyglandular auto immune disease, Addison's disease, pernicious anemia, celiac sprue.
Note: Investigators are not mandated to test for Celiac disease (also known as Sprue).
Patients suspected of having Celiac disease should be tested for the presence of
disease, as part of good medical care, as treatment would differ. Treated, stable
Hashimoto's thyroiditis is not exclusionary.
4. Any of the following abnormal laboratory values at screening: total white blood cell
count (WBC) outside the range of 1,500-15,000/mm3 (1.5-15.0 x 109/L), neutrophil count
(<1500/mm3) (<1.5 X 109 / L), lymphocyte count <500/mm3 (<0.5 X 109 / L), hemoglobin
(Hgb) <8.0 g/dL, platelets <100,000/mm3 (<100 x 109/L) 5. History of immunodeficiency
disorders, such as HyperIgM syndrome; history of recurrent infections suggestive of
immunodeficiency disorders.
6. History of or active coagulation disorder with increased thromboembolic risk; a PTT and
PT/ INR below lower limit of normal prior to inclusion.
7. Tuberculosis infection assessed by positive QuantiFERON TB-Gold test (QFT) at screening.
Subjects with a positive QFT test may participate in the study if further work up
(according to local practice/guidelines) establishes conclusively that the subject has no
evidence of active tuberculosis. If presence of latent tuberculosis is established, then
anti tuberculosis treatment must have been initiated and maintained according to local
country guidelines.
8. Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface
antigen (HBsAg) test, at screening, excludes a subject. Subjects with a positive HCV
antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV
RNA should be excluded.
9. Positive human immune virus HIV test (ELISA and Western Blot) at screening. 10. Evidence
of EBV, CMV, HSV, and/or SARS-CoV-2 infection by viral load above laboratory upper limit of
normal or only positive IgM serology in the absence of positive IgG at screening.
Rescreening is permitted in persistently asymptomatic or postsymptomatic subjects, but
study drug must be able to be administered within 100 days of diagnosis of T1D.
11. Major dental work (e.g. tooth extractions or dental surgery with access to dental pulp)
within 8 days of first dose; febrile illness within 48 hrs of first dose.
12. Use of other investigational drugs or use of immunosuppressive agents at the time of
enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has
returned to baseline, whichever is longer; or longer if required by local regulations.
13. History of multiple and recurring allergies or allergy to the investigational
compound/compound class being used in this study. Multiple and recurring allergies refer to
known allergies to the investigational compound, to immunoglobulin based therapies, or to
multiple drug classes. Dust mites, hay fever, and similar environmental allergies are not
exclusionary.
14. History of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g.
human monoclonal antibody.
15. History of malignancy of any organ system (other than localized basal cell carcinoma of
the skin), treated or untreated, within 5 years of screening, regardless of whether there
is evidence of local recurrence or metastases.
16. Active serious psychiatric disorders (diagnosed or treated by a psychiatrist), such as
eating disorders and psychosis or history thereof.
17. Any complicating medical issues or clinically abnormal laboratory results that may
cause an increased safety risk to the subject as judged by the investigator.
18. Ongoing, and up to 2 weeks prior to screening, use of medications that may affect
glucose control (e.g, systemic steroids, thiazides, beta blockers). A short course of oral
steroids <10 days if medically required is permissible with sponsor notification.
19. History of drug abuse, nicotine or harmful alcohol use within 12 months prior to first
dose, or evidence (as determined by the investigators) of such abuse at screening. For
example, harmful alcohol use in adults is defined as five or more drinks per day for 5 or
more days in the past 30 days. Harmful alcohol use by adolescents (age 13-18 years) is to
be determined by the investigator, based on local culture and laws. Any alcohol use by
children (age 6-12) is a disqualifier. Harmful cannabinoid use is difficult to define
universally and the determination of abuse will be made by the Investigator based on local
culture and law.
20. Taking medications prohibited by the protocol 21. Pregnant or nursing (lactating)
women, where pregnancy is defined as the state of a female after conception and until the
termination of gestation, confirmed by a positive hCG laboratory test.
22. Women of child-bearing potential, defined as all women, who are sexually active,
physiologically capable of becoming pregnant (e.g. menstruating), unless they are using
highly effective methods of contraception during dosing and for 14 weeks after stopping the
investigational drug. Highly effective contraception methods include:
- Total abstinence from heterosexual intercourse (when this is in line with the
preferred and usual lifestyle of the subject). Periodic abstinence (e.g. calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception.
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to first
dose. In case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment.
- Male sterilization in the sexual partner of female study participant (at least 6
months prior to screening). For female subjects on the study the vasectomized male
partner should be the sole partner for that subject.
- Use of oral (estrogen and progesterone), injected or implanted hormonal methods of
contraception or placement of an intrauterine device (IUD) or intrauterine system
(IUS) or other forms of hormonal contraception that have comparable efficacy (failure
rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
- In case of use of oral contraception, women should be stable on the same pill for a
minimum of 3 months prior to first dose.
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