HDV-Insulin Lispro for Type 1 Diabetes

(OPTI-2 Trial)

Not currently recruiting at 26 trial locations

Overseen By Robert Geho, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Diasome Pharmaceuticlas, Inc.

Must be taking: Insulin

Must not be taking: Hydroxyurea, Noninsulin glucose-lowering

Disqualifiers: Pregnancy, Liver abnormalities, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating Type 1 diabetes by directing insulin straight to the liver. The aim is to determine if this approach can better control low blood sugar compared to regular insulin injections. Participants will be divided into two groups: one will use the new liver-targeting insulin (HDV-Insulin Lispro), and the other will continue with their usual insulin. Individuals diagnosed with Type 1 diabetes for at least six months, who use insulin, and are willing to use a continuous glucose monitor (a device that tracks blood sugar levels) may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to use the study-provided insulin as their only bolus insulin and insulin degludec as their basal insulin. You cannot use noninsulin glucose-lowering medications other than metformin, and you must stop any weight loss medications or supplements 30 days before the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that HDV-Insulin Lispro was well-tolerated in past studies for people with Type 1 diabetes, with no major safety issues identified. Studies suggest that targeting insulin to the liver might reduce low blood sugar events without affecting overall blood sugar control, indicating that HDV-Insulin Lispro is safe to use.

Regular Lispro insulin, the comparator in this trial, is already widely used for diabetes treatment, with well-known side effects and risks.

Overall, previous research suggests that both treatments in this study are safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 diabetes?

Researchers are excited about HDV-Insulin Lispro for Type 1 Diabetes because it offers a novel approach to insulin delivery. Unlike standard insulins like Lispro, which are well-known for managing blood sugar levels, HDV-Insulin Lispro uses a unique delivery technology that potentially enhances insulin absorption and action. This could lead to more efficient blood sugar control and fewer fluctuations, which are significant challenges for people with Type 1 Diabetes. By improving how quickly and effectively insulin works, this treatment has the potential to improve daily management and overall quality of life for patients.

What evidence suggests that this trial's treatments could be effective for Type 1 diabetes?

Research shows that HDV-Insulin Lispro, which targets the liver, may help people with Type 1 diabetes manage blood sugar more effectively. In this trial, participants will join different treatment arms. One arm will receive HDV-Insulin Lispro. An earlier study found that patients using HDV-Insulin Lispro required about 25% less mealtime insulin compared to those using regular insulin lispro, while maintaining similar blood sugar levels. This suggests that HDV-Insulin Lispro could control blood sugar more efficiently. Additionally, some studies have found that patients using this insulin experienced fewer episodes of low blood sugar. These findings indicate that HDV-Insulin Lispro might be a promising option for better blood sugar management in Type 1 diabetes. ^{1 2 4 5 6}

Who Is on the Research Team?

Ruth Weinstock, MD

Principal Investigator

State University of New York - Upstate Medical University

Are You a Good Fit for This Trial?

This trial is for adults with Type 1 Diabetes who are already using Insulin Degludec. Participants should be willing to monitor their blood sugar continuously and work with doctors on dosing. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

Willing to use CGM device throughout the study

My A1C is between 6.5% and 9.0%, and I use 1.25 units or less of insulin per kilogram of my body weight daily.

I have Type 1 diabetes, use insulin, and my C-peptide level is below 0.6 nmol/L.

Exclusion Criteria

Received any investigational drug within prior 90 days

I haven't used diabetes or weight loss medications or supplements in the last 30 days.

Known or specific allergy to any component of the study drug, the active comparator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 3 weeks

Run-in

Assess eligibility and transition to use of insulin lispro and insulin degludec with unmasked continuous glucose monitoring

2 weeks

Dose Optimization

Optimize bolus and basal insulin doses

12 weeks

Maintenance

Maintain optimized insulin doses and monitor glycemic control

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HDV-Insulin Lispro
• Lispro

Trial Overview

The study compares HDV-Insulin Lispro, which targets the liver, against regular Insulin Lispro in managing blood sugar levels in Type 1 diabetes patients over a period of up to 32 weeks.

How Is the Trial Designed?

Group I: HDV Lispro (HDV-L) Experimental Treatment 1 Intervention

Subjects in this arm will use degludec as their daily basal insulin, and HDV-lispro as their bolus insulin

Group II: Lispro (LIS) Active Control 1 Intervention

Subjects in this arm will use degludec as their daily basal insulin and lispro as their bolus insulin

HDV-Insulin Lispro is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Insulin Lispro for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in European Union as Insulin Lispro for:

• Diabetes mellitus

Approved in Canada as Insulin Lispro for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Diasome Pharmaceuticlas, Inc.

Lead Sponsor

Trials

1

Recruited

230+

Published Research Related to This Trial

In a 26-week study involving 176 participants with type 1 diabetes, HDV-insulin lispro (HDV-L) demonstrated noninferiority to standard insulin lispro (LIS) in controlling blood sugar levels, with no significant differences in hypoglycemia or insulin dosing overall.

However, HDV-L was associated with a lower incidence of severe hypoglycemia in participants with higher baseline A1C levels, suggesting that HDV-L may provide a safer option for those with poorer blood sugar control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes. Klonoff, D., Bode, B., Cohen, N., et al.[2022]

In a study involving 1008 patients, short-acting insulin lispro and regular insulin Humulin R showed similar effectiveness in controlling blood sugar levels and had comparable safety profiles, with no significant differences in hypoglycemia incidents.

After a year of continued lispro therapy, glycosylated hemoglobin (HbA1C) levels returned to baseline, indicating that while lispro was well tolerated in the short term, long-term efficacy may need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lispro insulin as premeal therapy in type 1 diabetes: comparison with Humulin R. Daniels, AR., Bruce, R., McGregor, L.[2022]

A comparison of insulin lispro and regular human insulin (Humulin R) in 3634 patients with type 1 and type 2 diabetes showed no significant differences in treatment-emergent adverse events, indicating similar safety profiles for both insulins.

Both insulin therapies did not differ in their effects on the progression of chronic diabetes complications, such as retinopathy, neuropathy, cardiovascular disease, or kidney disease, suggesting that insulin lispro is as safe as Humulin R.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. Glazer, NB., Zalani, S., Anderson, JH., et al.[2019]

Insulin lispro, a rapid-acting human insulin analog, is more effective than regular human insulin in controlling post-meal blood glucose levels and may reduce the risk of hypoglycemic episodes, particularly at night, in patients with type 1 diabetes.

Compared to regular human insulin, insulin lispro has a faster onset and shorter duration of action, which enhances dosing convenience and improves patients' quality of life by allowing for more flexible injection times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin lispro: its role in the treatment of diabetes mellitus. Campbell, RK., Campbell, LK., White, JR.[2017]

A 34-year-old woman with a systemic allergy to human insulin was able to tolerate insulin lispro, suggesting it may be a safe alternative for patients with similar allergies.

Insulin lispro produced a significantly lower allergic reaction compared to human insulin, and over time, the patient's reactivity to both types of insulin decreased, indicating that lispro has a reduced immunogenic potency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lispro analog for treatment of generalized allergy to human insulin. Kumar, D.[2019]

Insulin lispro (Humalog®) offers a faster and more effective way to control blood sugar levels after meals compared to human insulin, reducing the risk of delayed hypoglycemia, especially at night.

The new Humalog® 200 U/ml formulation is bioequivalent to the 100 U/ml version and is designed for patients needing more than 20 units of insulin per day, providing a more convenient injection experience with a novel pen design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Humalog® 200 U/ml KwikPen™]. Scheen, AJ.[2016]

In a study involving 24 Japanese patients with Dravet syndrome, adding stiripentol to their existing treatment of clobazam and valproate resulted in a 66.7% responder rate, with some patients experiencing a complete cessation of seizures.

Stiripentol was well tolerated, with only mild-to-moderate side effects reported, and it significantly reduced the duration of clonic or tonic-clonic seizures, indicating its efficacy as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of add-on stiripentol to clobazam and valproate in Japanese patients with Dravet syndrome: additional supportive evidence. Inoue, Y., Ohtsuka, Y.[2022]

In a study of 28 patients with Dravet syndrome, the addition of stiripentol (STP) significantly increased serum concentrations of valproate (VPA), indicating a potential interaction that requires careful monitoring during treatment.

Patients receiving both STP and topiramate (TPM) experienced marked increases in VPA levels, leading to severe side effects like anorexia and thrombocytopenia, highlighting the importance of adjusting VPA dosages in this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on stiripentol elevates serum valproate levels in patients with or without concomitant topiramate therapy. Jogamoto, T., Yamamoto, Y., Fukuda, M., et al.[2018]

In a study of 54 patients with Dravet syndrome, the long-term use of stiripentol (STP) combined with valproate (VPA) and clobazam (CLB) was maintained by 96% of participants due to its effectiveness in reducing seizure frequency and severity.

Despite the treatment, most patients (96%) continued to experience seizures, indicating that while the combination therapy is beneficial, achieving complete seizure freedom remains a challenge for the majority.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with dravet syndrome in the era of stiripentol: A French cohort cross-sectional study. De Liso, P., Chemaly, N., Laschet, J., et al.[2018]

In a study involving 82 children with Dravet syndrome, stiripentol significantly reduced overall seizure frequency and prolonged seizures, especially in those receiving it alongside other medications like clobazam and valproate.

Stiripentol was generally well-tolerated, with only 5% of patients discontinuing due to side effects, primarily sedation and reduced appetite, indicating it is a viable treatment option for managing seizures in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stiripentol in Dravet syndrome: results of a retrospective U.S. study. Wirrell, EC., Laux, L., Franz, DN., et al.[2018]

In a 12-week study involving 19 patients with insulin-dependent diabetes mellitus (IDDM), lispro insulin significantly reduced postprandial blood glucose levels, indicating its efficacy in improving metabolic control.

Lispro was found to be safe, with only one serious adverse event reported (ketoacidosis due to a dosing error) and mild hypoglycemic episodes in ten patients, suggesting it is a beneficial addition to insulin therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of insulin lispro in patients with diabetes mellitus. Cheţa, D., Străchinariu, R., Trifan, E., et al.[2022]

Insulin lispro (Humalog) is designed to be absorbed more quickly than regular insulin due to its modified amino acid sequence, which reduces self-association, leading to a faster onset of action.

This rapid absorption allows for better timing of insulin administration with meals, improving glycemic control after eating and reducing the risk of hypoglycemia before the next meal, as it can be injected just before eating rather than 30 minutes prior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin lispro: a new quick-acting insulin analogue. Gale, EA.[2019]

Stiripentol (STP) shows nonlinear pharmacokinetics, with younger children (under 6 years) having significantly lower serum concentrations compared to older patients, indicating that age affects how the drug is processed in the body.

Drug interactions are important; for instance, medications like phenobarbital and phenytoin can significantly reduce STP concentrations, while clobazam can moderately increase them, highlighting the need for careful therapeutic drug monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentrations of stiripentol in children and adults with epilepsy: the influence of dose, age, and comedication. May, TW., Boor, R., Mayer, T., et al.[2013]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31551249/

A 6-Month Phase 2b Study in Type 1 Diabetes

Among poorly controlled participants, bolus insulin doses at end point were ∼25% lower with HDV-L (P = 0.02), despite similar A1C outcomes; in better-controlled ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02794155

Study of HDV Insulin Versus Insulin in Type 1 Diabetes ...

This will be a Phase 2b, multicenter, randomized, double blind, titration clinical study, evaluating the efficacy and safety in the HDV Insulin Lispro Group ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9546184/

Reduced hypoglycaemia using liver‐targeted insulin in ...

Unexpectedly, participants with baseline HbA1c less than 8.5% exhibited no effect on either HbA1c or level 2 hypoglycaemia with the use of HDV‐insulin lispro.

4.

diabetesjournals.org

diabetesjournals.org/care/article/42/11/2154/36351/Divergent-Hypoglycemic-Effects-of-Hepatic-Directed

Divergent Hypoglycemic Effects of Hepatic-Directed Prandial ...

We report here a 6-month randomized, double-blind, noninferiority study of HDV-insulin lispro (HDV-L) compared with insulin lispro (LIS) in conjunction with ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03096392?term=Insulin%20lispro%20AND%20water&rank=1

Comparison of Hepatic Directed Vesicle (HDV)-Insulin ...

This is a double blind, active comparator controlled multiple dose safety, tolerability and efficacy study comparing HDV insulin lispro with insulin lispro ...

6.

diasome.com

diasome.com/articles/hdv-technology-primary-endpoint-in-phase-2b

n

In subjects with baseline HbA1C ≥8.5% treated with HDV-L there was a ~0.5% HbA1C decrease from baseline (comparable to control Lispro) with ~25% less bolus ...