HM15136 for Congenital Hyperinsulinism

Recruiting at 8 trial locations

Overseen By JinHee Byeon

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Hanmi Pharmaceutical Company Limited

Must be taking: Standard care medications

Must not be taking: Systemic glucocorticoids, Insulin

Disqualifiers: Diabetes, Pheochromocytoma, Insulinoma, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HM15136 (also known as Efpegerglucagon or LAPSGlucagon Analog) for individuals with congenital hyperinsulinism (CHI), a condition where the body produces excessive insulin, leading to low blood sugar. The goal is to determine if adding HM15136 to regular treatments can better manage blood sugar levels. Participants should have CHI with persistent low blood sugar despite their current treatment plan. This study is open to those who have undergone surgery or are managing CHI without surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop your current medications, but you need to be on stable standard of care treatment. You cannot use drugs that interfere with the study drug or glucose metabolism, like systemic glucocorticoids or insulin.

Is there any evidence suggesting that HM15136 is likely to be safe for humans?

Research shows that HM15136, a new treatment for congenital hyperinsulinism (CHI), appears promising in early studies. In past research, HM15136 helped maintain stable blood sugar levels over time, suggesting it could serve as a helpful once-a-week treatment for CHI.

Regarding safety, HM15136 seems well-tolerated. Studies with overweight or obese adults found the treatment to be safe. These adults had other health issues but did not experience any major safety problems with HM15136.

While the safety of HM15136 in humans is still under investigation, early results are encouraging. More research is needed to fully understand its safety. This current trial aims to provide more information about how well people tolerate HM15136 and its safety when used with standard treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for congenital hyperinsulinism?

Researchers are excited about HM15136 for treating congenital hyperinsulinism because it offers a new approach compared to standard treatments like diazoxide and octreotide. Unlike these medications, which help control insulin levels by different mechanisms, HM15136 is designed to target the underlying causes of excessive insulin production more directly. This innovative approach could potentially lead to better management of blood sugar levels with fewer side effects, making it a promising option for those with this condition.

What evidence suggests that HM15136 might be an effective treatment for congenital hyperinsulinism?

Research has shown that HM15136, a new medication similar to glucagon, may help treat congenital hyperinsulinism (CHI). In animal studies, it maintained normal blood sugar levels, suggesting potential benefits for humans. Early results from human studies indicated that patients using HM15136 achieved better blood sugar control. This trial will evaluate HM15136, which uses a longer-lasting form of glucagon to balance blood sugar more effectively. Overall, these findings suggest that HM15136 could significantly advance CHI management. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 2 years or older with Congenital Hyperinsulinism who still have low blood sugar despite current treatments. They may have had surgery or be managed without it, and must not have diabetes or use medications that affect blood sugar levels.

Inclusion Criteria

I am on a stable standard treatment plan, with or without extra nutrition.

I have had most of my pancreas removed or am being treated without surgery because I can't have pancreatic surgery.

I am 2 years or older with CHI and still have low blood sugar despite treatment.

Exclusion Criteria

I've had CHI treatment with IV glucose or glucagon in the last 3 months.

My low blood sugar is not caused by medications or other known reasons.

I am not currently using any medications that could affect the study drug or my blood sugar levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HM15136 (efpegerglucagon) once weekly for 8 weeks as add-on therapy to standard of care treatment

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HM15136

Trial Overview The study tests HM15136 as an additional weekly treatment to see if it's safe and effective in managing low blood sugar in patients with CHI. It will also look at how the body processes the drug across different ages.

How Is the Trial Designed?

Group I: HM15136 active Experimental Treatment 1 Intervention

Cohort 1 / Cohort 2

Who Is Running the Clinical Trial?

Hanmi Pharmaceutical Company Limited

Lead Sponsor

Trials

196

Recruited

62,100+

Young Choi

Hanmi Pharmaceutical Company Limited

Chief Medical Officer since 2023

PhD in Pharmacology from Yonsei University

Jae-Hyun Park

Hanmi Pharmaceutical Company Limited

Chief Executive Officer since 2024

MD from Seoul National University

Published Research Related to This Trial

In a trial involving 32 children with congenital hyperinsulinism, dasiglucagon, when added to standard care, significantly reduced the frequency of hypoglycemia episodes detected by continuous glucose monitoring by 43% compared to standard care alone.

Dasiglucagon was found to be safe and well tolerated, although it did lead to more skin and gastrointestinal side effects compared to standard care alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasiglucagon for the treatment of congenital hyperinsulinism: a randomised phase 3 trial in infants and children. Thornton, PS., De Leon, DD., Empting, S., et al.[2023]

In a study of 31 Polish patients with congenital hyperinsulinism of infancy (CHI), it was found that CHI is associated with increased birth weight, lower Apgar scores, and a high rate of perinatal complications (74%) and neurological implications (48%).

The study proposed a novel clinical algorithm to standardize management, which includes prioritizing pharmacotherapy, genetic screening, and diagnostic imaging, aiming to optimize treatment and reduce complications, as inconsistent diagnostic and therapeutic approaches were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management? Buraczewska, M., Szymanska, E., Brandt, A., et al.[2017]

A new antibody antagonist, TB-222-023, has been developed that is more potent than the existing GLP-1R antagonist, exendin-(9-39), in reducing insulin secretion in models of congenital hyperinsulinism (HI).

This innovative therapy effectively increased plasma glucose levels and decreased the insulin to glucose ratio in mouse models and human islets, suggesting it could be a promising treatment option for patients with diazoxide-unresponsive HI, who currently face limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a Glucagon-Like Peptide 1 Receptor Antagonist Antibody for Treatment of Hyperinsulinism. Peterson, SM., Juliana, CA., Hu, CF., et al.[2023]

HM15136, a novel long-acting glucagon analog, shows significantly improved solubility and stability compared to natural glucagon, making it a promising therapeutic option for congenital hyperinsulinism (CHI).

In animal studies, HM15136 demonstrated a much longer half-life (36 hours) and effectively reversed hypoglycemia, suggesting it could be developed as a once-weekly treatment for managing blood glucose levels in CHI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism. Heo, YH., Kim, JK., Lee, JS., et al.[2023]

After near-total pancreatectomy for diffuse congenital hyperinsulinism, 59% of children experienced mild hypoglycemia that typically resolved within 5 years, but many also developed hyperglycemia, with 100% incidence by 13 years post-surgery.

In contrast, children with focal congenital hyperinsulinism had a much better outcome, with rare and transient hypoglycemia or hyperglycemia, indicating that limited surgery can effectively cure this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. Beltrand, J., Caquard, M., Arnoux, JB., et al.[2022]

CRN02481, a selective SST5 agonist, effectively reduced insulin secretion and prevented fasting hypoglycemia in a mouse model of congenital hyperinsulinism (KATP-HI), demonstrating its potential as a new treatment option for this condition.

The compound also showed efficacy in suppressing insulin secretion from healthy human islets and islets from infants with KATP-HI, indicating its broad applicability in managing hyperinsulinism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A selective nonpeptide somatostatin receptor 5 agonist effectively decreases insulin secretion in hyperinsulinism. Juliana, CA., Chai, J., Arroyo, P., et al.[2023]

In a pilot study involving 9 infants with congenital hyperinsulinism (K(ATP)HI), the GLP-1 receptor antagonist exendin-(9-39) significantly increased fasting blood glucose levels, indicating its potential to help manage hypoglycemia in these patients.

The study suggests that targeting the GLP-1 receptor could be a promising therapeutic approach for treating children with K(ATP)HI, as exendin-(9-39) effectively inhibited insulin secretion in response to amino acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. Calabria, AC., Li, C., Gallagher, PR., et al.[2022]

In a study of 54 individuals with congenital hyperinsulinism treated with lanreotide, the therapy significantly increased the duration of fasting with plasma glucose levels above 70 mg/dL, improving from an average of 5.1 hours to 8.6 hours (P = 0.001).

Lanreotide was found to be well-tolerated, with 42% of patients able to discontinue other treatments, although some side effects like subcutaneous nodules (26%) and gallstones (11%) were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Lanreotide in the Treatment of Congenital Hyperinsulinism. Cuff, H., Lord, K., Ballester, L., et al.[2022]

Citations

1. nature.com nature.com/articles/s41598-022-21251-y

A novel glucagon analog with an extended half-life ... A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism. Yong Ho ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511771/

Treatment of Congenital Hyperinsulinism With a Novel ... Outcome and Follow-up. The patient has continued to demonstrate improvement in glycemic control while on efpegerglucagon. This has been ...

3. hanmipharm.com hanmipharm.com/science/pipeline/focused/hm15136.hm

efpegerglucagon | Pipeline Safety and efficacy of efpegerglucagon in patients with congenital hyperinsulinism: interim results from a phase 2 study. European Society for Paediatric ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04732416

HM15136 (Efpegerglucagon) Treatment for 8 Weeks in ... This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of HM15136 when used as add-on therapy in subjects with CHI ...

5. withpower.com withpower.com/trial/phase-3-congenital-hyperinsulinism-9-2021-4e5f0?condition=HH&overallStatus=Recruiting&hasNoPlacebo=false

HM15136 for Congenital Hyperinsulinism This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of HM15136 when used as add-on therapy in subjects with CHI ...

6. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15162

Safety, tolerability, pharmacokinetics and pharmacodynamics ... This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.