Clinical Trial Results:
A phase 2, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of 400 mg twice a day oral ladarixin in patients with new-onset type 1 diabetes and preserved β-cell function at baseline.
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Summary
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EudraCT number |
2020-002966-15 |
Trial protocol |
DE IT BE |
Global end of trial date |
11 Oct 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2024
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First version publication date |
18 Dec 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LDX0419
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04899271 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Dompé farmaceutici S.P.A.
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Sponsor organisation address |
Via S. Lucia 6, Milan, Italy, 20122
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Public contact |
dr. Enrico M. Minnella, Dompé farmaceutici S.P.A., Dompé farmaceutici S.P.A., +39 583831, clinical.trials@dompe.com
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Scientific contact |
dr. Enrico M. Minnella,Dompé farmaceutici S.P.A., Dompé farmaceutici S.P.A., +39 02 583831, clinical.trials@dompe.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jul 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Apr 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Oct 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The objective of this clinical trial was to assess whether ladarixin treatment is effective to improve glycemic control in newly
diagnosed Type 1 Diabetes (T1D) adult patients with preserved β-cell function.
The safety of ladarixin in the specific clinical setting was also evaluated
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP; ICH GCP E6(R2)), the Declaration of Helsinki and all other applicable local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Dec 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 2
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Country: Number of subjects enrolled |
Serbia: 6
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Italy: 11
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Worldwide total number of subjects |
25
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
25
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The number of patients randomized and treated was lower than planned in the study protocol. The Sponsor decided to stop patient enrolment on 28 March 2022, due to the recruitment rate being lower than expected. At the time of recruitment closure, 25 patients had been randomized compared with the 75 planned. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Overall, 80 patients were screened and enrolled in the study. Out of these, 55 patients were not randomized due to failure to meet randomization criteria (52, 65.0%) and consent withdrawal (3, 3.8%). | ||||||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Blinding implementation details |
Patients, Investigators and site staff remained blinded to treatment assignment throughout the study.
The realization of the double-blind design was made possible by the production of placebo capsules identical in appearance to the active IMP, including packaging and labelling.
The treatment assignment info was kept confidential and not disclosed to any other persons than the ones involved in emergency and safety procedures, i.e., Investigators and Dompé Pharmacovigilance contact persons.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Ladarixin | ||||||||||||||||||
Arm description |
The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Ladarixin
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Investigational medicinal product code |
LDX
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Ladarixin was to be administered 400 mg b.i.d. as hard gelatine capsules for oral administration (2 capsules 200 mg each, b.i.d., at least 2 hours apart from breakfast or dinner) for 13 cycles of 14 days on/14 days off
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
The control group received matched placebo with the same schedule of IMP | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo was administered orally with the formulation and the same scheme of administration of LDX to preserve blinding.
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Baseline characteristics reporting groups
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Reporting group title |
Ladarixin
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Reporting group description |
The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
The control group received matched placebo with the same schedule of IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Ladarixin - FAS
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Full Analysis Set: it consisted of all randomized patients who received at least 1 dose of the IMP (either ladarixin or placebo). The FAS
was analyzed according to the Intention To Treat (ITT) principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy
strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.
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Subject analysis set title |
Ladarixin - SAF
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
SAF population: The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.
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Subject analysis set title |
Placebo - FAS
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP. The FAS was analyzed according to the ITT
principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of
the study and to present results on efficacy data.
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Subject analysis set title |
Placebo - SAF
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.
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End points reporting groups
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Reporting group title |
Ladarixin
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Reporting group description |
The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) | ||
Reporting group title |
Placebo
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Reporting group description |
The control group received matched placebo with the same schedule of IMP | ||
Subject analysis set title |
Ladarixin - FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full Analysis Set: it consisted of all randomized patients who received at least 1 dose of the IMP (either ladarixin or placebo). The FAS
was analyzed according to the Intention To Treat (ITT) principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy
strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.
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Subject analysis set title |
Ladarixin - SAF
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
SAF population: The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.
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Subject analysis set title |
Placebo - FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP. The FAS was analyzed according to the ITT
principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of
the study and to present results on efficacy data.
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Subject analysis set title |
Placebo - SAF
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.
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End point title |
Proportion of Patients With HbA1c <7% and Daily Insulin Requirement <0.50 IU/Kg/Day at month 12 | |||||||||
End point description |
The sample size of the study is calculated on the “proportion of patients with a HbA1c < 7% and daily insulin
requirement <0.50 IU/Kg/day”, a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114),
considering a larger effect size expected from the longer treatment length (one year versus 3 months).
The time frame for the primary endpoint has been set at Month 12 (Week 52) in order to evaluate the potential of
ladarixin effects on a long-term projection. Please note that proportion is expressed as count of patients.
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End point type |
Primary
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End point timeframe |
Month 12 (52±2 weeks)
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Statistical analysis title |
Ladarixin vs placebo | |||||||||
Comparison groups |
Placebo - FAS v Ladarixin - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.807 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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End point title |
Proportion of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day, at months 6 and 18 | |||||||||||||||
End point description |
The sample size of the study is calculated on the “proportion of patients with a HbA1c < 7% and daily insulin
requirement <0.50 IU/Kg/day”, a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114),
considering a larger effect size expected from the longer treatment length (one year versus 3 months). Follow-up is
extended up to 18 months to evaluate the potential persistency of any glycemic benefit. Please note that proportion is expressed as count of patients.
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End point type |
Secondary
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End point timeframe |
Month 6 (26±2 weeks) and Month 18 (78±2 weeks).
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||
Statistical analysis description |
comparison at month 6
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.746 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||
Statistical analysis description |
comparison at month 18
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.201 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
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End point title |
Proportion of Patients With a Reduction in HbA1c% > 0.5% From Baseline and Daily Insulin Requirement <0.50 IU/Kg at months 6, 12 and 18 | ||||||||||||||||||
End point description |
Proportion of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg/day
was calculated. Please note that proportion is expressed as count of patients.
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End point type |
Secondary
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End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
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Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 6
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Comparison groups |
Placebo - FAS v Ladarixin - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.867 | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 12
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.769 | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 18
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.776 | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
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End point title |
Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at months 6, 12 and 18 | |||||||||||||||||||||
End point description |
C-peptide level is a widely used measure of pancreatic beta-cell function and the MMTT is one of the methods for its
estimation. AUC stands for Area Under the Curve.
AUC calculation was based on actual rather scheduled timings and it was calculated using the trapezoidal rule. Cpeptide
0-120 min AUC (nmol/L) values were calculated based on all Basal-120min C-peptide values. Unscheduled
assessments were excluded from the analysis.
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End point type |
Secondary
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End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
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| Notes [1] - month 6: n=16 month 12: n=15 month 18: n=15 |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 6 for change from baseline
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.521 [2] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
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| Notes [2] - Assumption of normality was confirmed by Kolmogorov-Smirnov test; the comparison between treatment arms was performed by means of two-sample t-test. |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 12 for change from baseline
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.959 [3] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
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| Notes [3] - Assumption of normality was confirmed by Kolmogorov-Smirnov test; the comparison between treatment arms was performed by means of two-sample t-test. |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 18 for change from baseline
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.773 [4] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
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| Notes [4] - Assumption of normality was confirmed by Kolmogorov-Smirnov test; the comparison between treatment arms was performed by means of two-sample t-test. |
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End point title |
Changes From Baseline in HbA1c Levels at Months 6, 12 and 18. | |||||||||||||||||||||
End point description |
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. An A1C test measures the percentage of red blood cells that have
glucose-coated hemoglobin.
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End point type |
Secondary
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End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
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| Notes [5] - n= 15 at months 6 and 18 n=14 at month 12 [6] - n=6 at months 12 and 18 |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 6 for change from baseline
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.691 [7] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
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| Notes [7] - Assumption of normality is confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample t-test. |
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Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 12 for change from baseline
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Comparison groups |
Ladarixin - FAS v Placebo - FAS
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.685 [8] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [8] - Assumption of normality is confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample t-test. |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 18 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.64 [9] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [9] - Assumption of normality is confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample t-test. |
||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Proportion of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events during treatment at months 6, 12 and 18 | ||||||||||||||||||
End point description |
For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms:
memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure,
seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was
associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v.
glucose, or glucagon administration. Please note that proportion is expressed as count of patients.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Months 6 (week 26), 12 (week 52) and 18 (week 78)
|
||||||||||||||||||
|
|||||||||||||||||||
| Notes [10] - n=15 at months 6 and 18 n=14 at month 12 [11] - n=6 at month 18 |
|||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 6
|
||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
||||||||||||||||||
Number of subjects included in analysis |
25
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.867 [12] | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
| Notes [12] - Comparison between treatment arms is performed by means of a Chi-squared test. |
|||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 12
|
||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
||||||||||||||||||
Number of subjects included in analysis |
25
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.769 [13] | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
| Notes [13] - Comparison between treatment arms is performed by means of a Chi-squared test. |
|||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | ||||||||||||||||||
Statistical analysis description |
Comparison at month 18
|
||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
||||||||||||||||||
Number of subjects included in analysis |
25
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.577 [14] | ||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
| Notes [14] - Comparison between treatment arms is performed by means of a Chi-squared test. |
|||||||||||||||||||
|
||||||||||
End point title |
Number of Self-reported Episodes of Severe Hypoglycemia | |||||||||
End point description |
For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms:
memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure,
seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was
associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v.
glucose, or glucagon administration.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From baseline to study termination (month 18, week 78)
|
|||||||||
|
||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||
Number of subjects included in analysis |
25
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 1.271 | |||||||||
Method |
Cox proportional hazards model. | |||||||||
Confidence interval |
||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) to months 6, 12 and 18 | |||||||||||||||||||||
End point description |
For the purpose of this study, daily insulin is averaged over the previous 3 days.Insulin requirement (IU/kg/day
averaged over the previous 3 days) was to be recorded to Months 6, 12 and 18.
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
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [15] - n=16 at month 6 n= 15 at months 12 and 18 [16] - n=6 at month 6 |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 6 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.32 [17] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [17] - Assumption of normality is not confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample Mann–Whitney U test. |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 12 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.398 [18] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [18] - Assumption of normality is not confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample Mann–Whitney U test. |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 18 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 1 [19] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [19] - Assumption of normality is not confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample Mann–Whitney U test. |
||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline in Estimated Glucose Disposal Rate (eGDR) to months 6, 12 and 18 | |||||||||||||||||||||
End point description |
Estimated Glucose Disposal Rate (eGDR) is a marker for the Assessment of Insulin Resistance and a validated clinical
tool for estimating insulin sensitivity in type 1 diabetes.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [20] - n=15 at months 6 and 18 n= 14 at month 12 [21] - n=6 at months 12 and 18 |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 6 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.892 [22] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [22] - Assumption of normality is confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample t-test. |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 12 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.412 [23] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [23] - Assumption of normality is confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample t-test. |
||||||||||||||||||||||
Statistical analysis title |
Ladarixin vs placebo | |||||||||||||||||||||
Statistical analysis description |
Comparison at month 18 for change from baseline
|
|||||||||||||||||||||
Comparison groups |
Ladarixin - FAS v Placebo - FAS
|
|||||||||||||||||||||
Number of subjects included in analysis |
25
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.371 [24] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
| Notes [24] - Assumption of normality is not confirmed by Kolmogorov-Smirnov test; comparison between treatment arms is performed by means of two-sample Mann–Whitney U test. |
||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious | ||||||||||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with
the trial intervention.
A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or
prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Throughout the study up to 18 months
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Hypoglycemic blood glucose levels for patients reporting severe hypoglycemia | |||||||||||||||||||||
End point description |
A severe hypoglycemic event was defined as an event with 1 of the following symptoms: “memory loss, confusion, uncontrollable
behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms”, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL or
prompt recovery after oral carbohydrate, i.e. glucose, or glucagon administration. Summary statistics of blood glucose level
(mg/dL) are provided by treatment group at each time point for patients reporting severe hypoglycemia.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up
(Month 18)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ladarixin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The treatment group received 400 mg b.i.d. for 13 cycles of 14 days on/14 days off. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The control group received matched placebo with the same schedule of IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The enrolment was stopped on March,28, 2022 due to low enrolment rate, at the randomization of the 25th patient. Due to the trial early termination, efficacy analyses were reduced given the limited sample size of the study vs the one expected. | |||
