Type I DiabetesPhase 2NCT05035368

Ladarixin as Adjunctive Therapy to Improve Insulin Sensitivity and Glucometabolic Outcomes in Type 1 Diabetes

A Phase 2 study testing Ladarixin in people with Type I Diabetes, run by Dompé Farmaceutici S.p.A at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Objectives Primary study objective: To determine whether orally-administered ladarixin versus placebo adjunctive therapy improves insulin sensitivity in overweight, insulin-resistant (IR) type 1 Diabetic (T1D) adult subjects. Read more about this study

Who is it for?: Ages 21 to 65 years
Conditions the study is for: Type I Diabetes
What is being tested?: Ladarixin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 30 Sep 2021to Jun 2023
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

clinical diagnosis of autoimmune T1D as documented by positive T1D diabetes-related autoantibodies [the presence at diagnosis of at least one or more of - Insulin autoantibodies (IAA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc Transporter 8 (ZnT8) must be documented from medical records or new laboratory measurement (not including IAA)];
age 21-65 years at the time of consent;
T1D duration =>5 years;
current insulin standard of care (ISOC), either use of an insulin pump or a stable dose level and dose frequency (i.e. established dose range that does not fluctuate beyond 1SD of the median over a period of the last two months prior to enrollment), multiple daily injections of insulin (at least 3 injections per day) for the last two months prior to enrollment, with no plans to switch the modality of insulin administration during the 4 months following screening (e.g., injection user switching to a pump, pump user switching to injections);
HbA1c between 7.5%-10.0%, inclusive, as per results of screening laboratory measurement;
evidence of IR based on a total daily insulin dose >0.8 U/kg/ day and/or a screening estimated glucose disposal rate (eGDR) < 9 mg/kg/min 1-3 value strongly indicative of IR, sex- and ageadjusted;

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subject is overweight or obese with a BMI of between 25-40 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 written informed consent prior of any study-related procedure not part of standard medical care.

Who cannot join

patients with known or suspected hypersensitivity to 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);
use of medications for weight reduction (such as: Belviq (lorcaserin), Qsymia (Phentermine + topiramate), Orlistat (xenical));
use of a medication such as stimulants, antidepressants and/or psychotropic agents that could affect weight gain or glycemic control of T1D;
subject is on treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index [i.e., phenytoin, warfarin, and high dose of amitriptyline (>50 mg/day)];
any medications known to influence glucose tolerance (e.g. beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin, etc.);

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evidence of cardiac QTcF > 470 msec and/or any history of significant cardiovascular disease/abnormality;
any condition, including unstable dietary approach and disordered eating behaviour patterns, 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 (females) based on serum test (quantitative beta hCG) at screening; unwillingness to use effective contraceptive measures up to 2 months following trial discharge (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 spermicide foam).
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;
history of ≥1 severe hypoglycemic events (cognitive impairment that required assistance to treat) in the past 6 months;
hypoalbuminemia defined as 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 (CKDEPI) creatinine equation;
poor accessibility to veins for blood collection;
past (within 1 month prior to randomization) or current administration of any immunosuppressive medications (including oral, inhaled or systemically injected steroids) and use of any investigational agents, including any agents that impact the immune response or the cytokine system;
condition which interferes with the ability to accurately determine glycated HbA1c. Examples include: Genetic variants (e.g. HbS trait, HbC trait), elevated fetal hemoglobin (HbF) and chemically modified derivatives of hemoglobin (e.g. carbamylated Hb in patients with renal failure); Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic anemia); Iron deficiency anemia, iron replacement therapy;
significant systemic infection during the 4 weeks before the first 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-bycase basis by the investigator regarding whether they are serious enough to warrant exclusion).

Trial locations and contacts

1 site in 1 country.

United States1 site

Institute of Cellular Therapeutics Allegheny Health Network
Pittsburgh, Pennsylvania, 15212

Other trials in United States

About this study

Official title: Ladarixin 400 mg Twice a Day as Adjunctive Therapy to Improve Insulin Sensitivity and Glucometabolic Outcomes in Overweight Insulin-resistant Type 1 Diabetic Patients

Secondary study objectives: To determine whether orally-administered ladarixin versus placebo adjunctive therapy is safe and well-tolerated in overweight, IR T1D adult subjects.

Read the detailed description

This study is a randomized, placebo-controlled, double-blinded, 2-arm, 2-period crossover phase II trial using the CXCR1/CXCR2 chemokine receptor antagonist ladarixin versus placebo as adjunctive therapy to insulin to improve insulin sensitivity as well as glucometabolic outcomes in adult, insulin-requiring, overweight, IR T1D patients.

This trial will randomize 38 male and female patients 21-65 years of age, inclusive, with established insulinrequiring T1D and IR. After a 2:1 randomization into a treatment sequence (either ladarixin followed by placebo, or placebo followed by ladarixin, respectively), patients will be followed up for a maximum of 53 weeks.

The study database will be locked when the last patient randomized has completed visit 9 (week 52/53) and data have been cleaned.

Conditions: Type I Diabetes
Being tested: Ladarixin, Placebo
Keywords: Type I diabetes, Insulin-resistance, Overweight
Medical subject headings: Diabetes Mellitus, Type 1, Insulin Resistance, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LadarixinDrug
Also called LDX
Ladarixin will be administered orally at the dose of 400 mg twice a day at about 12-hour interval (morning and evening).
PlaceboOther
Placebo is administered with the same schedule of Ladarixin.

Study groups in NCT05035368
Study group	Role	What they receive
Ladarixin - placebo	Experimental	In this arm the treatment sequence is ladarixin 400 mg twice-a-day, followed by placebo, as adjunctive therapy to insulin in overweight, IR, T1D patients. IMP will be administered for 24 weeks in each treatment period with a 21-day washout between the two periods. (Ladarixin 24 weeks, washout 21 days, Placebo 24 weeks). Receives: Drug: Ladarixin; Other: Placebo
Placebo - Ladarixin	Experimental	In this arm the treatment sequence is placebo followed by ladarixin 400 mg twice-a-day, as adjunctive therapy to insulin in overweight, IR, T1D patients. IMP will be administered for 24 weeks in each treatment period with a 21-day washout between the two periods. (Placebo 24 weeks, washout 21 days, Ladarixin 24 weeks). Receives: Drug: Ladarixin; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

The mean difference in glucose infusion rate (GIR) from baseline
The glucose infusion rate (GIR) is a measure of the rate at which the patient receives intravenous administration of dextrose, which increases blood sugar levels. GIR is expressed in mg per kilogram body weight per minute (mg/Kg/min).
Measured: Week 25 of each treatment period (visits 4 and 8)

Secondary outcomes (2)

Change from baseline of HbA1c levels
In this study glycated hemoglobin (HbA1c) must be between 7.5%-10.0%, inclusive, as per results of screening laboratory measurement.
Measured: Week 25/26 (no later than 10 days after the last IMP dose) of each treatment period (visits 5 and 9)
Change in average (previous 3 days) daily insulin requirements
In this study insulin requirement is calculated as IU/kg/day averaged over the previous 3 days.
Measured: Week 25/26 (no later than 10 days after the last IMP dose) of each treatment period (visits 5 and 9)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 2021Jun 2023

First posted5 Sep 2021
Study start30 Sep 2021
Primary completionJun 2023 (estimated)
Study completionJun 2023 (estimated)

Why it stopped: Dompé decided to withdraw LDX0121 following an internal re-planning and an extensive review of the study design. At the time of withdrawal, no site had been activated and the drug had not been sent to investigators. No patients had been enrolled.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Type I DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: This study is a randomized, placebo-controlled, double-blinded, 2-arm, 2-period crossover phase II trial using the CXCR1/CXCR2 chemokine receptor antagonist ladarixin versus placebo as adjunctive therapy to insulin to improve insulin sensitivity as well as glucometabolic outcomes in adult, insulin-requiring, overweight, IR T1D patients. This trial will randomize 38 male and female patients 21-65 years of age, inclusive, with established insulin requiring T1D and IR. After a 2:1 randomization into a treatment sequence (either ladarixin followed by placebo, or placebo followed by ladarixin, respectively), patients will be followed up for a maximum of 53 weeks.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05035368
Sponsor's protocol ID: LDX0121
Status last verified: Jan 2022
First submitted: 30 Aug 2021
Last updated: 22 Dec 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Type I Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Ladarixin 400 mg Twice a Day as Adjunctive Therapy to Improve Insulin Sensitivity and Glucometabolic Outcomes in Overweight Insulin-resistant Type 1 Diabetic Patients
ClinicalTrials.gov ID: NCT05035368
Acronym / sponsor ID: LDX0121
Conditions: Type I Diabetes
Keywords: Type I diabetes, Insulin-resistance, Overweight
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Dompé decided to withdraw LDX0121 following an internal re-planning and an extensive review of the study design. At the time of withdrawal, no site had been activated and the drug had not been sent to investigators. No patients had been enrolled.
Enrolment: 0 participants (actual)
Lead sponsor: Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
Study start: 30 Sep 2021 (actual)
Primary completion: Jun 2023 (estimated)
Study completion: Jun 2023 (estimated)
First posted: 5 Sep 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Secondary study objectives: To determine whether orally-administered ladarixin versus placebo adjunctive therapy is safe and well-tolerated in overweight, IR T1D adult subjects.

Detailed description

The study database will be locked when the last patient randomized has completed visit 9 (week 52/53) and data have been cleaned.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: This study is a randomized, placebo-controlled, double-blinded, 2-arm, 2-period crossover phase II trial using the CXCR1/CXCR2 chemokine receptor antagonist ladarixin versus placebo as adjunctive therapy to insulin to improve insulin sensitivity as well as glucometabolic outcomes in adult, insulin-requiring, overweight, IR T1D patients. This trial will randomize 38 male and female patients 21-65 years of age, inclusive, with established insulin requiring T1D and IR. After a 2:1 randomization into a treatment sequence (either ladarixin followed by placebo, or placebo followed by ladarixin, respectively), patients will be followed up for a maximum of 53 weeks.

Arm	Type	Receives
Ladarixin - placebo	Experimental	Drug: Ladarixin, Other: PlaceboIn this arm the treatment sequence is ladarixin 400 mg twice-a-day, followed by placebo, as adjunctive therapy to insulin in overweight, IR, T1D patients. IMP will be administered for 24 weeks in each treatment period with a 21-day washout between the two periods. (Ladarixin 24 weeks, washout 21 days, Placebo 24 weeks).
Placebo - Ladarixin	Experimental	Drug: Ladarixin, Other: PlaceboIn this arm the treatment sequence is placebo followed by ladarixin 400 mg twice-a-day, as adjunctive therapy to insulin in overweight, IR, T1D patients. IMP will be administered for 24 weeks in each treatment period with a 21-day washout between the two periods. (Placebo 24 weeks, washout 21 days, Ladarixin 24 weeks).

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

clinical diagnosis of autoimmune T1D as documented by positive T1D diabetes-related autoantibodies [the presence at diagnosis of at least one or more of - Insulin autoantibodies (IAA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc Transporter 8 (ZnT8) must be documented from medical records or new laboratory measurement (not including IAA)];
age 21-65 years at the time of consent;
T1D duration =>5 years;
current insulin standard of care (ISOC), either use of an insulin pump or a stable dose level and dose frequency (i.e. established dose range that does not fluctuate beyond 1SD of the median over a period of the last two months prior to enrollment), multiple daily injections of insulin (at least 3 injections per day) for the last two months prior to enrollment, with no plans to switch the modality of insulin administration during the 4 months following screening (e.g., injection user switching to a pump, pump user switching to injections);
HbA1c between 7.5%-10.0%, inclusive, as per results of screening laboratory measurement;

Key exclusion criteria (19 listed)

patients with known or suspected hypersensitivity to 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);
use of medications for weight reduction (such as: Belviq (lorcaserin), Qsymia (Phentermine + topiramate), Orlistat (xenical));
use of a medication such as stimulants, antidepressants and/or psychotropic agents that could affect weight gain or glycemic control of T1D;
subject is on treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index [i.e., phenytoin, warfarin, and high dose of amitriptyline (>50 mg/day)];

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LadarixinAlso: LDXLadarixin will be administered orally at the dose of 400 mg twice a day at about 12-hour interval (morning and evening).	Drug	Ladarixin - placebo, Placebo - Ladarixin
PlaceboPlacebo is administered with the same schedule of Ladarixin.	Other	Ladarixin - placebo, Placebo - Ladarixin

Primary outcome

The mean difference in glucose infusion rate (GIR) from baseline
Time frame: Week 25 of each treatment period (visits 4 and 8)
The glucose infusion rate (GIR) is a measure of the rate at which the patient receives intravenous administration of dextrose, which increases blood sugar levels. GIR is expressed in mg per kilogram body weight per minute (mg/Kg/min).

2 secondary outcomes

Change from baseline of HbA1c levels
Time frame: Week 25/26 (no later than 10 days after the last IMP dose) of each treatment period (visits 5 and 9)
Change in average (previous 3 days) daily insulin requirements
Time frame: Week 25/26 (no later than 10 days after the last IMP dose) of each treatment period (visits 5 and 9)

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2023.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nick Giannoukakis, PhD principal investigator

Allegheny General Hospital and West-Penn Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ladarixin in people with Type I Diabetes, run by Dompé Farmaceutici S.p.A at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The mean difference in glucose infusion rate (GIR) from baseline (time frame: Week 25 of each treatment period (visits 4 and 8)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05035368.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2023.