Trial Outcomes & Findings for A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients With New-onset Type 1 Diabetes (NCT NCT02814838)

Last Updated: 2024-04-19

Results Overview

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2. Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of \>200mg/dL or \<70mg/dL. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at week 13+/-1 The 2-hour C-peptide AUC after the MMTT at Week 13±1 was transformed as log(x+1) values.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

week 13±1

Results posted on

2024-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Ladarixin Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo Placebo oral capsule Placebo: Placebo oral capsule
Overall Study STARTED	50	26
Overall Study COMPLETED	48	25
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Ladarixin Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo Placebo oral capsule Placebo: Placebo oral capsule
Overall Study 3 agreed dates for the final visit missed	1	0
Overall Study Consent withdrawal	1	1

Baseline Characteristics

A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients With New-onset Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ladarixin n=50 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule	Total n=76 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	50 Participants n=5 Participants	26 Participants n=7 Participants	76 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	10 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	16 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	26 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Belgium	20 participants n=5 Participants	11 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Italy	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Germany	13 participants n=5 Participants	5 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: week 13±1

Population: ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)

Outcome measures

Outcome measures
Measure	Ladarixin n=49 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Area Under the Curve (AUC)(0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Week 13	4.026 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.4852	3.886 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.7446

SECONDARY outcome

Timeframe: Follow-ups at Weeks 26±2 and 52±2

Population: ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2. Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of \>200mg/dL or \<70mg/dL. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at week 13+/-1. The 2-hour C-peptide AUC after the MMTT at Week 13±1 was transformed as log(x+1) values.

Outcome measures

Outcome measures
Measure	Ladarixin n=47 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=25 Participants Placebo oral capsule Placebo: Placebo oral capsule
Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52 FU week 26	3.9351 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.51710	3.8076 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.76473
Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52 FU week 52	3.6371 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.75222	3.6380 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.81268

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

Population: ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2. Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of \>200mg/dL or \<70mg/dL. The test was initiated before 10 a.m. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink (Nestlé Nutrition) up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15±5, 30±5, 60±10, 90±10, 120±15, 180±15 min after the meal.

Outcome measures

Outcome measures
Measure	Ladarixin n=49 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=25 Participants Placebo oral capsule Placebo: Placebo oral capsule
Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT FU week 13	5.7818 percentage of change Standard Deviation 36.74477	-6.0734 percentage of change Standard Deviation 38.22179
Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT FU week 26	-0.8701 percentage of change Standard Deviation 42.93044	-13.7347 percentage of change Standard Deviation 37.41900
Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT FU week 52	-22.2532 percentage of change Standard Deviation 38.84672	-24.2215 percentage of change Standard Deviation 42.67277

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded in the interval from randomization to Week 13±1, Week 13±1 to Week 26±2, and Week 26±2 to Week 52±2. From enrolment, patients were admitted to intensive diabetes management, according to current ADA recommendation \[2014\]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick): * pre-prandial blood glucose of 70-130 mg/dL * post-prandial blood glucose \< 180 mg/dL * bed-time blood glucose of 110-150 mg/dL Telephone calls (outside scheduled visits) were scheduled on a regular basis to ensure optimization of metabolic control.

Outcome measures

Outcome measures
Measure	Ladarixin n=47 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Change From Screening in Average (Previous 3 Days) Insulin Requirement FU week 13	-0.067 IU/kg/day Standard Deviation 0.1774	-0.018 IU/kg/day Standard Deviation 0.1314
Change From Screening in Average (Previous 3 Days) Insulin Requirement FU week 26	-0.011 IU/kg/day Standard Deviation 0.2625	0.032 IU/kg/day Standard Deviation 0.1699
Change From Screening in Average (Previous 3 Days) Insulin Requirement FU week 52	0.025 IU/kg/day Standard Deviation 0.2507	0.101 IU/kg/day Standard Deviation 0.2411

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests.

Outcome measures

Outcome measures
Measure	Ladarixin n=48 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=25 Participants Placebo oral capsule Placebo: Placebo oral capsule
Change From Screening in Glycated Haemoglobin (HbA1c) Levels FU week 13	-1.40 percentage of glycated haemoglobin Standard Deviation 1.674	-1.18 percentage of glycated haemoglobin Standard Deviation 1.352
Change From Screening in Glycated Haemoglobin (HbA1c) Levels FU week 26	-1.19 percentage of glycated haemoglobin Standard Deviation 2.003	-0.63 percentage of glycated haemoglobin Standard Deviation 1.141
Change From Screening in Glycated Haemoglobin (HbA1c) Levels FU week 52	-0.69 percentage of glycated haemoglobin Standard Deviation 2.225	-0.76 percentage of glycated haemoglobin Standard Deviation 1.333

SECONDARY outcome

Timeframe: Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2

Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively; Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below.

Outcome measures

Outcome measures
Measure	Ladarixin n=50 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - Basal average	0.218 nmol/L Standard Deviation 0.1087	0.225 nmol/L Standard Deviation 0.1416
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 15 min	0.294 nmol/L Standard Deviation 0.1621	0.299 nmol/L Standard Deviation 0.1779
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 30 min	0.422 nmol/L Standard Deviation 0.2126	0.452 nmol/L Standard Deviation 0.3036
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 60 min	0.545 nmol/L Standard Deviation 0.2631	0.537 nmol/L Standard Deviation 0.2354
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 90 min	0.613 nmol/L Standard Deviation 0.2467	0.581 nmol/L Standard Deviation 0.2486
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 120 min	0.620 nmol/L Standard Deviation 0.2559	0.656 nmol/L Standard Deviation 0.2923
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT Screening - 180 min	0.527 nmol/L Standard Deviation 0.2252	0.550 nmol/L Standard Deviation 0.2277
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - Basal average	0.231 nmol/L Standard Deviation 0.1136	0.210 nmol/L Standard Deviation 0.1315
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 15 min	0.300 nmol/L Standard Deviation 0.1385	0.285 nmol/L Standard Deviation 0.1956
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 30 min	0.427 nmol/L Standard Deviation 0.2048	0.392 nmol/L Standard Deviation 0.2418
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 60 min	0.571 nmol/L Standard Deviation 0.2660	0.523 nmol/L Standard Deviation 0.2729
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 90 min	0.620 nmol/L Standard Deviation 0.2859	0.594 nmol/L Standard Deviation 0.3176
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 120 min	0.637 nmol/L Standard Deviation 0.2869	0.601 nmol/L Standard Deviation 0.3050
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 13 - 180 min	0.518 nmol/L Standard Deviation 0.2302	0.527 nmol/L Standard Deviation 0.2778
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - Basal average	0.212 nmol/L Standard Deviation 0.0941	0.207 nmol/L Standard Deviation 0.1192
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 15 min	0.278 nmol/L Standard Deviation 0.1294	0.260 nmol/L Standard Deviation 0.1426
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 30 min	0.391 nmol/L Standard Deviation 0.1857	0.368 nmol/L Standard Deviation 0.2150
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 60 min	0.534 nmol/L Standard Deviation 0.2463	0.511 nmol/L Standard Deviation 0.2967
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 90 min	0.569 nmol/L Standard Deviation 0.2606	0.552 nmol/L Standard Deviation 0.3101
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 120 min	0.592 nmol/L Standard Deviation 0.2703	0.552 nmol/L Standard Deviation 0.2907
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 26 - 180 min	0.504 nmol/L Standard Deviation 0.2189	0.466 nmol/L Standard Deviation 0.2362
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - Basal average	0.168 nmol/L Standard Deviation 0.1070	0.178 nmol/L Standard Deviation 0.1068
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 15 min	0.228 nmol/L Standard Deviation 0.1606	0.249 nmol/L Standard Deviation 0.1616
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 30 min	0.321 nmol/L Standard Deviation 0.2231	0.314 nmol/L Standard Deviation 0.1826
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 60 min	0.430 nmol/L Standard Deviation 0.2693	0.440 nmol/L Standard Deviation 0.2671
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 90 min	0.463 nmol/L Standard Deviation 0.2806	0.465 nmol/L Standard Deviation 0.2881
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 120 min	0.503 nmol/L Standard Deviation 0.3085	0.492 nmol/L Standard Deviation 0.2717
Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT week 52 - 180 min	0.426 nmol/L Standard Deviation 0.2341	0.443 nmol/L Standard Deviation 0.2441

SECONDARY outcome

Timeframe: Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2

Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively). Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below.

Outcome measures

Outcome measures
Measure	Ladarixin n=50 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - basal average	6.965 mmol/L Standard Deviation 1.6858	6.855 mmol/L Standard Deviation 1.9507
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 15 min	8.108 mmol/L Standard Deviation 1.8453	8.013 mmol/L Standard Deviation 2.0941
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 30 min	10.438 mmol/L Standard Deviation 2.2282	10.096 mmol/L Standard Deviation 2.4694
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 60 min	12.146 mmol/L Standard Deviation 2.9387	12.068 mmol/L Standard Deviation 2.9204
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 90 min	12.350 mmol/L Standard Deviation 3.4122	12.076 mmol/L Standard Deviation 3.9156
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 120 min	11.400 mmol/L Standard Deviation 3.4561	11.827 mmol/L Standard Deviation 4.0204
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Screening - 180 min	9.478 mmol/L Standard Deviation 3.6320	9.652 mmol/L Standard Deviation 4.0549
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - Basal average	7.074 mmol/L Standard Deviation 1.9973	6.644 mmol/L Standard Deviation 2.1145
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 15 min	8.231 mmol/L Standard Deviation 2.1415	7.836 mmol/L Standard Deviation 2.2409
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 30 min	10.727 mmol/L Standard Deviation 2.5691	10.224 mmol/L Standard Deviation 2.3600
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 60 min	12.614 mmol/L Standard Deviation 3.1536	12.871 mmol/L Standard Deviation 2.6908
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 90 min	12.553 mmol/L Standard Deviation 3.7998	13.092 mmol/L Standard Deviation 3.1608
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 120 min	11.773 mmol/L Standard Deviation 4.0990	12.260 mmol/L Standard Deviation 3.7590
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 13 - 180 min	9.761 mmol/L Standard Deviation 3.9834	9.984 mmol/L Standard Deviation 3.8597
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - Basal average	7.496 mmol/L Standard Deviation 2.0261	7.600 mmol/L Standard Deviation 2.6387
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 15 min	8.750 mmol/L Standard Deviation 2.0827	9.058 mmol/L Standard Deviation 2.7026
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 30 min	10.927 mmol/L Standard Deviation 2.3901	11.240 mmol/L Standard Deviation 2.6187
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 60 min	13.494 mmol/L Standard Deviation 2.8623	14.222 mmol/L Standard Deviation 2.8795
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 90 min	13.665 mmol/L Standard Deviation 3.8399	15.020 mmol/L Standard Deviation 3.4469
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 120 min	13.240 mmol/L Standard Deviation 4.1302	14.424 mmol/L Standard Deviation 3.7761
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 26 - 180 min	10.956 mmol/L Standard Deviation 4.2031	12.028 mmol/L Standard Deviation 3.8832
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - Basal average	7.457 mmol/L Standard Deviation 2.3045	8.163 mmol/L Standard Deviation 2.2251
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 15 min	8.939 mmol/L Standard Deviation 2.7210	9.544 mmol/L Standard Deviation 2.2230
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 30 min	11.374 mmol/L Standard Deviation 2.6806	11.688 mmol/L Standard Deviation 2.6411
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 60 min	14.315 mmol/L Standard Deviation 3.1205	14.725 mmol/L Standard Deviation 2.9631
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 90 min	14.911 mmol/L Standard Deviation 3.5768	15.276 mmol/L Standard Deviation 3.7144
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 120 min	14.354 mmol/L Standard Deviation 3.9162	15.140 mmol/L Standard Deviation 3.7514
Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT Week 52 - 180 min	12.148 mmol/L Standard Deviation 4.0817	13.148 mmol/L Standard Deviation 3.9136

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

A severe hypoglycaemic event was defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level \<54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

Outcome measures

Outcome measures
Measure	Ladarixin n=50 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit FU week 13	0.0 events Standard Deviation 0.0	0.0 events Standard Deviation 0.0
Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit FU Week 26	0.0 events Standard Deviation 0.14	0.0 events Standard Deviation 0.20
Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit FU Week 52	0.1 events Standard Deviation 0.32	0.0 events Standard Deviation 0.20

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

Population: ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)

Maintenance of a residual ß-cell function is defined as at least one MMTT C-peptide value \> 0.2 nmol/L. Proportion is reported as Percentage of patients.

Outcome measures

Outcome measures
Measure	Ladarixin n=49 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
Proportion of Patients Maintaining a Residual β-cell Function FU Week 13	96.0 Percentage of patients Interval 86.29 to 99.51	88.5 Percentage of patients Interval 69.85 to 97.55
Proportion of Patients Maintaining a Residual β-cell Function FU week 26	86.0 Percentage of patients Interval 73.26 to 94.18	84.6 Percentage of patients Interval 65.13 to 95.64
Proportion of Patients Maintaining a Residual β-cell Function FU Week 52	78.0 Percentage of patients Interval 64.04 to 88.47	76.9 Percentage of patients Interval 56.35 to 91.03

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1, 26±2 and 52±2

Population: ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)

A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level \<54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients. Events per patient are calculated from the date of randomisation.

Outcome measures

Outcome measures
Measure	Ladarixin n=49 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=25 Participants Placebo oral capsule Placebo: Placebo oral capsule
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit FU Week 13	90.0 Percentage of patients Interval 78.19 to 96.67	73.1 Percentage of patients Interval 52.21 to 88.43
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit FU week 26	78.0 Percentage of patients Interval 64.04 to 88.47	50.0 Percentage of patients Interval 29.93 to 70.07
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit FU Week 52	62.0 Percentage of patients Interval 47.17 to 75.35	53.8 Percentage of patients Interval 33.37 to 73.41

SECONDARY outcome

Timeframe: Follow-ups at Weeks 13±1 26±2 and 52±2

The means are all "adjusted means". The MMTT over the study: logAUC(15-120 min) of C-peptide above fasting value at Weeks 13±1, 26±2, and 52±2 is reported. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at weeks 13+/-1, 26±2 and 52±2

Outcome measures

Outcome measures
Measure	Ladarixin n=50 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 Participants Placebo oral capsule Placebo: Placebo oral capsule
C-peptide AUC(15 to 120 Mins) Above Fasting Value FU week 52	2.9733 log(ng*hr/ml [15-120 min]+1) Interval 2.715 to 3.2316	2.9282 log(ng*hr/ml [15-120 min]+1) Interval 2.572 to 3.2844
C-peptide AUC(15 to 120 Mins) Above Fasting Value FU Week 13	3.3736 log(ng*hr/ml [15-120 min]+1) Interval 3.173 to 3.5742	3.2334 log(ng*hr/ml [15-120 min]+1) Interval 2.9568 to 3.51
C-peptide AUC(15 to 120 Mins) Above Fasting Value FU week 26	3.2419 log(ng*hr/ml [15-120 min]+1) Interval 3.0186 to 3.4652	3.0649 log(ng*hr/ml [15-120 min]+1) Interval 2.7562 to 3.3735

SECONDARY outcome

Timeframe: Follow-up at Weeks 13±1, 26±2, and 52±2.

A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening \<median value. All the AUC analyses were based on actual rather than scheduled timings and were calculated using the trapezoidal rule. If the actual time was not recorded, the scheduled time was used instead. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal. The 2-hour C-peptide AUC after the MMTT was transformed as log(x+1) values.

Outcome measures

Outcome measures
Measure	Ladarixin n=26 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=11 Participants Placebo oral capsule Placebo: Placebo oral capsule
Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value FU Week 13	3.8085 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.45692	3.4543 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.86632
Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value FU Week 26	3.8202 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.48142	3.3178 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.91906
Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value FU Week 52	3.3796 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.68616	3.1562 log(ng*hr/ml [0-2 h]+1) Standard Deviation 0.97130

SECONDARY outcome

Timeframe: Follow-up at Weeks 13±1, 26±2, and 52±2.

Outcome measures

Outcome measures
Measure	Ladarixin n=26 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=11 Participants Placebo oral capsule Placebo: Placebo oral capsule
Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value FU week 13	3.1590 log(ng*hr/ml [15-120 min] +1) Standard Deviation 0.56135	2.7959 log(ng*hr/ml [15-120 min] +1) Standard Deviation 1.07745
Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value FU week 26	27.7841 log(ng*hr/ml [15-120 min] +1) Standard Deviation 15.10337	18.6842 log(ng*hr/ml [15-120 min] +1) Standard Deviation 15.46837
Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value FU week 52	2.7993 log(ng*hr/ml [15-120 min] +1) Standard Deviation 0.82214	19.9415 log(ng*hr/ml [15-120 min] +1) Standard Deviation 16.95597

SECONDARY outcome

Timeframe: Follow-up at Weeks 13±1, 26±2, and 52±2

A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level \<54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients, despite the measure type indicated is "number". Events per patient are calculated from the date of randomisation.

Outcome measures

Outcome measures
Measure	Ladarixin n=26 Participants Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=11 Participants Placebo oral capsule Placebo: Placebo oral capsule
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value FU week 13	88.5 Percentage of patients Interval 69.85 to 97.55	63.6 Percentage of patients Interval 30.79 to 89.07
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value FU week 26	88.5 Percentage of patients Interval 69.85 to 97.55	36.4 Percentage of patients Interval 10.93 to 69.21
Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value FU week 52	65.4 Percentage of patients Interval 44.33 to 82.79	45.5 Percentage of patients Interval 16.75 to 76.62

Adverse Events

Ladarixin

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ladarixin n=50 participants at risk Ladarixin oral capsule Ladarixin: Ladarixin oral capsule	Placebo n=26 participants at risk Placebo oral capsule Placebo: Placebo oral capsule
Gastrointestinal disorders Gastrointestinal disorder	2.0% 1/50 • Number of events 1 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years	0.00% 0/26 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Injury, poisoning and procedural complications Clavicle fracture	2.0% 1/50 • Number of events 1 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years	0.00% 0/26 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Injury, poisoning and procedural complications Laceration	0.00% 0/50 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years	3.8% 1/26 • Number of events 1 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Metabolism and nutrition disorders Hyperglycaemia	2.0% 1/50 • Number of events 1 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years	0.00% 0/26 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Psychiatric disorders mental disorder	2.0% 1/50 • Number of events 1 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years	0.00% 0/26 • AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years

Other adverse events

Additional Information

Clinical Development & Operations

Dompé Farmaceutici SpA

Phone: +39 02 583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place