Trial Outcomes & Findings for Study of Safety and Efficacy of CFZ533 in Type 1 Diabetes Pediatric and Young Adult Subjects (NCT NCT04129528)

Last Updated: 2025-04-08

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

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.

Results posted on

2025-04-08

Participant Flow

Participants took part in 12 investigative sites in 6 countries.

Enrolment was based on both screening and baseline results. The screening and baseline visit(s) may be conducted over 1 or more visits depending on the subject's body weight and World Health Organization and European Medicines Agency (EMA) recommendations for trial related phlebotomy limits.

Participant milestones

Participant milestones
Measure	CFZ533 CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Overall Study STARTED	29	15
Overall Study COMPLETED	26	13
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	CFZ533 CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Overall Study Adverse Event	1	0
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 Participants Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.	Total n=44 Participants Total of all reporting groups
Age, Continuous	15.6 years STANDARD_DEVIATION 2.81 • n=93 Participants	15.5 years STANDARD_DEVIATION 3.07 • n=4 Participants	15.5 years STANDARD_DEVIATION 2.86 • n=27 Participants
Sex: Female, Male Female	10 Participants n=93 Participants	5 Participants n=4 Participants	15 Participants n=27 Participants
Sex: Female, Male Male	19 Participants n=93 Participants	10 Participants n=4 Participants	29 Participants n=27 Participants
Race/Ethnicity, Customized White	29 Participants n=93 Participants	15 Participants n=4 Participants	44 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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.

Population: The safety analysis set included all participants that received any study treatment.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 Participants Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period Adverse Events	28 Participants	13 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period Serious Adverse Events	4 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period AEs leading to discontinuation of study treatment	4 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Population: The full analysis set (FAS) included all participants to whom study treatment has been assigned by randomization.

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.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 Participants Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Normalized Stimulated C-peptide Area Under the Curve (AUC) at Week 52	0.42 nmol/L Interval 0.36 to 0.49	0.36 nmol/L Interval 0.3 to 0.44

SECONDARY outcome

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

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any dose of CFZ533 and with no protocol deviations that impact on PK data.

Cmax is defined as the maximum (peak) observed concentration following a dose. Free CFZ533 plasma concentrations were determined using a validated target-based sandwich enzyme-linked immunosorbent assay (ELISA) method.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Maximum Plasma Concentration (Cmax) of CFZ533 After Intravenous (IV) Administration	506 ug/mL Standard Deviation 124	—

SECONDARY outcome

Timeframe: 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.

Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval. Free CFZ533 plasma concentrations were determined using a validated target-based sandwich ELISA method.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Trough Plasma Concentration (Ctrough) of CFZ533 Day 1	0.00 ug/mL Standard Deviation 0.00	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 4	182 ug/mL Standard Deviation 40.9	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 8	171 ug/mL Standard Deviation 45.8	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 12	169 ug/mL Standard Deviation 43.1	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 16	193 ug/mL Standard Deviation 55.2	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 20	184 ug/mL Standard Deviation 68.1	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 24	176 ug/mL Standard Deviation 65.2	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 28	186 ug/mL Standard Deviation 61.4	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 32	177 ug/mL Standard Deviation 65.4	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 36	180 ug/mL Standard Deviation 86.7	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 40	183 ug/mL Standard Deviation 80.0	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 44	170 ug/mL Standard Deviation 88.7	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 48	205 ug/mL Standard Deviation 101	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 52	155 ug/mL Standard Deviation 111	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 56	72.6 ug/mL Standard Deviation 53.3	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 60	30.9 ug/mL Standard Deviation 24.9	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 64	9.23 ug/mL Standard Deviation 11.7	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 68	1.86 ug/mL Standard Deviation 3.15	—
Trough Plasma Concentration (Ctrough) of CFZ533 Week 72	0.221 ug/mL Standard Deviation 0.499	—

SECONDARY outcome

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

Tmax is the time to reach maximum (peak) drug concentration after single-dose administration (time). Free CFZ533 plasma concentrations were determined using a validated target-based sandwich ELISA method. Theoretical sampling time points were used to report Tmax.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Time to Reach Maximum Plasma Concentration (Tmax) of CFZ533 After IV Administration	1.5 hours Interval 1.5 to 1.5	—

SECONDARY outcome

Timeframe: Week 52

Population: The full analysis set (FAS) included all participants to whom study treatment has been assigned by randomization.

Full remission is defined by HbA1c ≤ 6.5% (48 mmol/mol) and no exogenous insulin use at Week 52. Partial remission 1 is defined by Insulin Dose Adjusted HbA1c (IDAA1c) ≤ 9.0 at Week 52. Partial remission 2 is defined by HbA1c \< 7.0% (53 mmol/mol) and total daily insulin dose \<0.5 units per kg per day at Week 52. Two different criteria for partial remission were considered, and patients were assessed separately according to each criterion.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 Participants Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Number of Participants With Full or Partial Remission Full remission*	0 Participants	0 Participants
Number of Participants With Full or Partial Remission Partial remission 1	20 Participants	10 Participants
Number of Participants With Full or Partial Remission Partial remission 2	15 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

Population: The full analysis set (FAS) included all participants to whom study treatment has been assigned by randomization.

Outcome measures

Outcome measures
Measure	CFZ533 n=29 Participants CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 Participants Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.
Normalized Stimulated C-peptide Area Under the Curve (AUC) at Week 72	0.40 nmol/L Interval 0.34 to 0.47	0.32 nmol/L Interval 0.26 to 0.39

Adverse Events

CFZ533

Serious events: 6 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Total

Serious events: 7 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CFZ533 n=29 participants at risk CFZ533 30 mg/kg i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg received 195 mg s.c., and participants with body weight of ≥ 50 kg to ≤125 kg received 300 mg s.c. on a weekly basis.	Placebo n=15 participants at risk Placebo i.v. dose on Day 1. From Day 8 up to Day 358 participants with body weight of ≥30 to \<50 kg and body weight of ≥ 50 kg to ≤125 kg received matching placebo s.c. on a weekly basis.	Total n=44 participants at risk Total
General disorders Pyrexia	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Infections and infestations Large intestine infection	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Infections and infestations Mastoiditis	0.00% 0/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Infections and infestations Urinary tract infection	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Injury, poisoning and procedural complications Traumatic fracture	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Metabolism and nutrition disorders Diabetic metabolic decompensation	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Metabolism and nutrition disorders Hypoglycaemia	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Nervous system disorders Tonic clonic movements	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.4% 1/29 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.	2.3% 1/44 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 72 weeks.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER