Clinical Trial on Ladarixin Adjunctive Therapy to Improve Glycemic Control in Type 1 Diabetes.

NCT05368402 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: LDX01222022-000743-68
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

Primary objective \- To determine whether oral ladarixin versus placebo adjunctive therapy improves glycemic control in overweight, insulin resistant (IR) adult subjects with type 1 diabetes (T1D). Secondary objectives

• To ascertain the effect of ladarixin on glycemic variability as per CGM derived parameters.
• To determine the safety of oral ladarixin versus placebo adjunctive therapy in overweight, IR adult subjects with T1D.

Conditions

Type 1 Diabetes

Keywords

glycemic control; insulin-resistant type 1 diabetes.

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an HbA1c Reduction From Baseline of ≥0.50% (Absolute Difference) Without Episodes of Severe Hypoglycemia.

  Please note that this outcome is meant to express the "count" (number + %) of participants. Please also note that because of the low recruitment rate (out of the 24 participants screened, only 2 participants were enrolled, 1 in the ladarixin group and 1 in the placebo group), it was not possible to have a consistent sample size for any formal statistical analyses, accordingly no efficacy evaluation was conducted on the two randomized subjects' data. The low recruitment rate led the Sponsor decide to close enrollment on 04th August 2023 and thus to early terminate the study.

  At Visit 4 (week 27/28)

Secondary Outcomes (1)

• Number of Patients With Treatment Emergent Adverse Events (TEAEs) of Any Kind From the Beginning of Study Treatment to up to the End of Study Participation

  Throughout the study, up to week 26 (day 182)

Study Arms (2)

Ladarixin

EXPERIMENTAL

Ladarixin was administered orally at the dose of 400 mg b.i.d. for 7 cycles of 14 days with an interval of 14 days off, for a total duration of 26 weeks.

Drug: Ladarixin

Placebo

PLACEBO COMPARATOR

Matching placebo was administered with the same treatment schedule of the IMP.

Other: Placebo

Interventions

Ladarixin DRUG

The two daily oral doses of ladarixin (400 mg each dose) were administered at about a 12-hour interval (morning and evening; ideally between 6:30/11:30 and 18:30/23:30). At each administration, 2 capsules were swallowed with a glass of water, at least 2 hours apart from breakfast or dinner

Also known as: LDX

Ladarixin

Placebo OTHER

Placebo was administered with the same ladarixin schedule.

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of autoimmune T1D as documented by positive T1D-related autoantibodies \[the presence of at least one or more of Insulin autoantibodies (IAA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc Transporter 8 (ZnT8)\];
• age 21-65 years, inclusive, at the time of consent;
• T1D duration \> 1 year;
• detectable fasting C-peptide as per the result of screening laboratory measurement;
• current insulin standard of care (ISOC), either established use of an insulin pump (closed loop system excluded) or a stable dose level and dose frequency for the last two months prior to screening, with no plans to switch the modality of insulin administration during the trial;
• routine use of a self-owned (if applicable) Continuous Glucose Monitoring (CGM) system that can record glucose concentrations continuously for at least 7 days;
• HbA1c value \>7.5% as per the result of screening laboratory measurement;
• evidence of IR based on a total daily insulin dose \>0.8 U/kg/day;
• subject is overweight or obese as per body mass index (BMI) of between 24-33 kg/m2, inclusive;
• ability to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations, and willing to be contacted by clinical trial staff;
• provision of signed informed consent prior of any study-related procedure not part of standard medical care.

You may not qualify if:

• use of a "closed loop system" for integrated glucose reading/insulin infusion;
• known or suspected hypersensitivity to the active pharmaceutical ingredient, non-steroidal anti-inflammatory drugs or any excipient of the investigational medicinal products (e.g. lactose and croscarmellose) as well as patients with congenital lactase deficiency, galactosaemia or glucose-galactose intolerance will have to be excluded;
• use of non-insulin medications for adjunctive blood glucose control (e.g: antidiabetic agents such as metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors, SGLT-2 inhibitors or amylin) within one month of randomization as well as required in the participant's standard of care;
• use of medications for weight reduction such as: Belviq (lorcaserin), Qsymia (Phentermine + topiramate), Orlistat (xenical) within one month of randomization as well as required in the participant's standard of care;
• use of a medication such as stimulants, antidepressants and/or psychotropic agents that could affect weight gain or glycemic control of T1D;
• treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index \[i.e., phenytoin, warfarin, and high dose of amitriptyline (\>50 mg/day)\];
• use of angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin;
• evidence of QTcF \>470 msec and a history of significant cardiovascular disease/abnormality;
• any condition, including unstable diet and disordered eating behaviour, that in the judgment of the investigator will adversely affect patient's safety or the completion of the protocol or otherwise confound study outcome;
• pregnancy (subjects of child-bearing potential) based on serum test (quantitative beta hCG) at screening; unwillingness to use effective contraceptive measures up to 2 months following trial discharge (all participants);
• clinical diagnosis of celiac disease that is in poor control as defined by most recent tissue transglutaminase (tTG) that is in the abnormal range;
• history of ≥1 Diabetic Ketoacidosis (DKA) events in the past 6 months;
• hypoalbuminemia (serum albumin \<3 g/dL);
• hepatic dysfunction defined by increased ALT/AST \> 3 x upper limit of normal (ULN) and increased total bilirubin \> 3 mg/dL \[\>51.3 μmol/L\];
• moderate to severe renal impairment calculated by estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m2 as determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation;

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (2)

Ospedale F. Spaziani Frosinone

Frosinone, 03100, Italy

Location

Università Campus Bio-Medico di Roma (UCBM) Policlinico Universitario

Rome, 00128, Italy

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

On 4th August 2023, the Sponsor decided to close enrollment because of a low recruitment rate (as per Clinical Study Protocol). At that time two patients were randomized out of a total of 24 screened, while 86 patients were expected to be enrolled by December 2022. Given the low recruitment rate, no formal statistical analyses could be undertaken for assess IMP efficacy.

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé Farmaceutici SpA

clinicaltrials@dompe.com

+30 902 583831

Study Officials

• Paolo Pozzilli, MD

  Campus Bio-Medico di Roma (UCBM) Policlinico Universitario, Rome, Italy, 00128

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Appearance, including packaging and labelling, of the IMP (capsules, packaging) will not allow to recognize actual treatment (either ladarixin or placebo). During the trial, blinding will be broken by the Investigator for emergency purposes only, where knowledge of the blinded treatment could influence further patient care.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients across all genders, 21-65 years, inclusive, with established insulin-requiring T1D and IR, will be assigned (1:1) to receive either oral ladarixin 400 mg b.i.d. for 7 cycles (26 weeks) of 14 days on/14 days off (treatment group) or matched placebo (control group) for a total of 28 weeks.

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 10, 2022
• Study Start: September 14, 2022
• Primary Completion: September 18, 2023
• Study Completion: September 18, 2023
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)