Study to evaluate the effect and the safety of ladaraxin in adult and adolescent patients with recent onset type 1 diabetes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dompe' Farmaceutici S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

10 Dec 2020 → 22 Oct 2025

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dompe' Farmaceutici S.p.A.

External identifiers

EU CT number

2024-513560-26-00

EudraCT number

2020-001926-71

ClinicalTrials.gov

NCT04628481

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy, Pharmacokinetic, Pharmacodynamic

The objective of this clinical trial is to assess whether ladarixin treatment has an effect to preserve Beta-cell function and delay the progression of T1D in adolescent and adult patients. The safety of ladarixin in the specific clinical setting will be also evaluated.

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

Recent onset Type 1 Diabetes

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male and female patients aged 14-45 years, inclusive;
2. Recent onset T1D (1st IMP dose within 180 days from 1st insulin administration);
3. Positive for at least one diabetes-related auto-antibody (anti-GAD; IAA, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody; ZnT8);
4. Require, or has required at some time insulin therapy through one or more separate subcutaneous injections or Continuous Subcutaneous Insulin Infusion (CSII).
5. Fasting C peptide < 0.205nmol/L
6. Residual β-cell function as per peak stimulated (MMTT) C-peptide level >0.2nmol/L; MMTT should not be performed within one week of resolution of a diabetic ketoacidosis event
7. Patient able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
8. Patients who have given written informed consent prior of any study-related procedure not part of standard medical care (participants under the age of 18, shall provide an assent for the study as per country requirements). Specific consent must be given by adolescents to be selected for the full PK analysis.

Exclusion criteria 14

1. A type 2 diabetes diagnosis or any other unstable chronic disease for which dose adjustment of specific medication is anticipated during the trial
2. Moderate to severe renal impairment as per estimated Glomerular Filtration Rate (eGFR) 60 mL/min/1.73m2, as determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
3. Hepatic dysfunction defined by increased ALT/AST >3 x upper limit of normal (ULN) and increased total bilirubin >3 mg/dL [>51.3 μmol/L]
4. Hypoalbuminemia defined as serum albumin <3 g/dL
5. QTcF > 470 msec
6. Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks
7. A history of significant cardiovascular disease/abnormality
8. Known hypersensitivity to non-steroidal anti-inflammatory drugs
9. Concomitant treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index [i.e. phenytoin, warfarin, sulphanylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (>50 mg/day)]
10. Previous (past 2 weeks) and concomitant treatment withantidiabetic agents as metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors, SGLT-2 inhibitors or amylin, or any medications known to influence glucose tolerance (e.g. beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin, etc.)
11. Past (past month) or current administration of any immunosuppressive medications (including oral or systemic corticosteroids) and use of any investigational agents, including any agents that impact the immune response or the cytokine system
12. Significant systemic infection during the 4 weeks before the 1st dose of study drug (e.g., infection requiring hospitalization, major surgery, or i.v. antibiotics to resolve; other infections, e.g. bronchitis, sinusitis, localized cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion)
13. History of positive status for hepatitis A (IgM), hepatitis B (not due to immunization), hepatitis C and HIV
14. Pregnant or breast-feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males). Effective contraceptive measures include a hormonal birth control (e.g. oral pills, long term injections, vaginal ring, patch); the intrauterine device (IUD); a double barrier method (e.g. condom or diaphragm plus spermacide foam); abstinence.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Primary endpoint. Time frame: Month 6].

Secondary endpoints 10

1. Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Time frame: month 12, 18 and 24].
2. Change in HbA1c from baseline [Time frame: Month 6, 12, 18 and 24].
3. Time in range (TIR) by Continuous Glucose Monitoring (CGM) [Time frame: Month 6, 12, 18, 24].
4. Proportion of patients with HbA1c <7% who did not experience severe hypoglycemic events during treatment [Time frame: Month 6, 12, 18 and 24].
5. Average (previous 3 days) daily insulin requirement (IU/kg/day) [Time frame: Month 6, 12, 18 and 24].
6. Proportion of patients with HbA1c <7% and daily insulin requirement <0.5 (IU/kg/day) [Time frame: Month 6, 12, 18 and 24].
7. Additional Glucose Variability Indices derived from CGM (glucose AUC outside the target range of 70 – 180 mg/dL, 2-hour postprandial glucose (PPG), Mean Amplitude Glycemic Excursions (MAGE), continuous overall net glycemic action (CONGA)-n, Mean Of the Daily Differences (MODD), and mean daily blood glucose, SD (Standard Deviation). [Time frame: Month 6, 12, 18 and 24].
8. Number of self-reported episodes of severe hypoglycemia [Time frame: Month 6, 12, 18 and 24].
9. Percentage of patients not requiring insulin therapy [Time frame: Month 6, 12, 18 and 24]
10. Estimated Glucose Disposal Rate (eGDR) [Time frame: Month 6, 12, 18 and 24].

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dompe' Farmaceutici S.p.A.

Sponsor organisation

Dompe' Farmaceutici S.p.A.

Address

Via Santa Lucia 6

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Enrico Maria Minnelli

Public contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Enrico Maria Minnelli

Third parties 12

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications