Study of safety and efficacy of CFZ533 in type 1 diabetes pediatric and young adult subjects
- Conditions
- Treatment of subjects with type 1 diabetes mellitus with residual beta cell function (RBCF), with the goal of preserving RBCFMedDRA version: 21.1Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004553-25-SI
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 44
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 12 and 21 years (inclusive, and enrolled in stages) at screening.
3. Body weight range from 30 to 125 kg (inclusive).
4. Evidence of one or more type 1 diabetes autoantibody(ies) against:
glutamic acid decarboxylase (anti-GAD), protein tyrosine, phosphataselike 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. A negative pregnancy test at screening is required for all sexually mature female subjects prior to participation in the study.
9. Subject and/or guardian must be able to communicate well with the investigator, to understand and comply with the requirements of the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 44
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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), T2DM
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. 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 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; aPTT 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 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 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
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in the absence of positive IgG at screening. Rescreening permitted in
persistently asymptomatic or post-symptomatic subjects, but study drug
must be able to be administered within 100 days of diagnosis of T1D and
viral load must be negative and IgG titers positive.
11. Major dental work (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 trea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the safety and tolerability of CFZ533 in subjects with new onset T1DM.<br>• To evaluate effects of CFZ533 on pancreatic beta cell function in subjects with new-onset T1DM.;Secondary Objective: • To evaluate the pharmacokinetics of CFZ533 in subjects with new onset T1DM.<br>• To evaluate the treatment effect of CFZ533 on remission or partial remission in subjects with new onset T1DM.<br>• To evaluate durability of effects of CFZ533 on pancreatic beta cell function in subjects with new-onset T1DM.<br>;Primary end point(s): 1) Proportion of subjects with adverse events (AE)/serious adverse events (SAE) in treatment groups.<br><br>2) Stimulated C-peptide AUC by mixed meal tolerance test (MMTT).;Timepoint(s) of evaluation of this end point: 1) 16 months<br><br>2) 12 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Free CFZ533 plasma concentration.<br><br>2) Proportion of subjects with full or partial remission.<br><br>3) Stimulated C-peptide AUC by MMTT.;Timepoint(s) of evaluation of this end point: 1) day 1; 1 week; and 12 months<br><br>2) 12 months<br><br>3) 20 weeks from last dose