Study of Safety and Efficacy of CFZ533 in Type 1 Diabetes Pediatric and Young Adult Subjects

NCT04129528 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCFZ533X22072018-004553-25
• Study Type: interventional
• Target: 44
• Locations: 6 countries
• Sites: 12

Brief Summary

The study was a Phase 2, multicounty, multicenter, non-confirmatory, investigator- and subject masked, randomized, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of CFZ533 on preservation of residual pancreatic β-cell function in new onset T1DM in pediatric and young adult subjects.

Conditions

Type 1 Diabetes Mellitus

Keywords

T1DM

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period

  Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, and SAEs. On-treatment period is defined as from date of first administration of study treatment to 98 days after date of last administration of study treatment (including start and stop date).

  Adverse events were reported from first dose of study treatment to 98 days after last dose, up to a maximum duration of approximately 65 weeks.

• Normalized Stimulated C-peptide Area Under the Curve (AUC) at Week 52

  The mixed meal tolerance test (MMTT) has appropriate sensitivity to detect residual insulin secretion and beta cell function. In the MMTT, following an 8-10 hour overnight fast, a weight-based liquid meal provided as 6 mL/kg (maximum 360 mL) of mixed meal, ingested over 5 min with timed blood samples for glucose and C peptide determination obtained 10 min prior to ingestion (t = -10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 min after consumption of the liquid meal. The time collections for post load samples are based on the start time of the mixed meal. Stimulated C-peptide AUC by the standard MMTT, normalized by the duration of measurements, was analyzed with a mixed model repeated measures analysis.

  At Week 52, 10 min prior to ingestion, at start of ingestion, and at 15, 30, 60, 90, and 120 min after consumption of the liquid meal.

Secondary Outcomes (5)

• Maximum Plasma Concentration (Cmax) of CFZ533 After Intravenous (IV) Administration

  Day 1: Pre-dose and 90 minutes after the start of the IV infusion (duration of the infusion is 30 minutes).

• Trough Plasma Concentration (Ctrough) of CFZ533

  Pre-dose at: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72.

• Time to Reach Maximum Plasma Concentration (Tmax) of CFZ533 After IV Administration

  Day 1: Pre-dose and 90 minutes after the start of the IV infusion (duration of the infusion is 30 minutes).

• Number of Participants With Full or Partial Remission

  Week 52

• Normalized Stimulated C-peptide Area Under the Curve (AUC) at Week 72

  At Week 72, 10 min prior to ingestion, at start of ingestion, and at 15, 30, 60, 90, and 120 min after consumption of the liquid meal.

Study Arms (2)

CFZ533

ACTIVE COMPARATOR

Randomized in a 2:1 ratio: 2 Active / 1 Placebo

Drug: CFZ533

Placebo

PLACEBO COMPARATOR

Similar in appearance to active study drug

Other: Placebo

Interventions

CFZ533 DRUG

First dose is administered via intravenous infusion, subsequent doses are administered subcutaneously.

Also known as: Iscalimab

CFZ533

Placebo OTHER

Placebo for active drug

Placebo

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent, and if needed assent from the child on the trial, must be obtained before any assessment is performed.
• Males and females aged between 12 and 21 years (inclusive, and enrolled in stages) at screening.
• Body weight range from 30 to 125 kg (inclusive).
• 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.
• 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).
• 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).
• 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.
• Must be willing to comply with the standard of care for diabetes management.
• A negative pregnancy test at screening is required for all sexually mature female subjects prior to participation in the study.
• Subject and/or guardian must be able to communicate well with the investigator, to understand and comply with the requirements of the study.

You may not qualify if:

• 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.
• Diabetic ketoacidosis within 2 weeks of the baseline MMTT test.
• 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.
• \. 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.
• \. 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.
• \. 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 and viral load must be negative and IgG titers positive.
• \. 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.
• \. 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.
• \. History of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g. human monoclonal antibody.
• \. 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.
• \. Active serious psychiatric disorders (diagnosed or treated by a psychiatrist), such as eating disorders and psychosis or history thereof.
• \. Any complicating medical issues or clinically abnormal laboratory results that may cause an increased safety risk to the subject as judged by the investigator.
• \. 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.
• \. 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. 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.
• \. 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Brussels, 1090, Belgium

Location

Novartis Investigative Site

Edegem, 2650, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Augsburg, 86179, Germany

Location

Novartis Investigative Site

Florence, FI, 50139, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Ljubljana, 1525, Slovenia

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

Nottingham, NG7 2UH, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

iscalimab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: November 8, 2019
• Primary Completion: January 15, 2024
• Study Completion: June 4, 2024
• Last Updated: April 8, 2025
• Results First Posted: January 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); GB (1); BE (4); SL (1); ES (3); DE (1)