HM15136 for Congenital Hyperinsulinism

Recruiting at7 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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 with persistent hypoglycemia while on standard of care treatment (SoC). HM15136 will be administered once weekly in multiple doses to subjects in multiple age including pediatric to find appropriate exposure-response data.

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.

What data supports the effectiveness of the drug HM15136 for treating congenital hyperinsulinism?

Research shows that HM15136, a long-acting glucagon analog, is more soluble and stable than natural glucagon, and it effectively normalizes glucose levels in rodent models of congenital hyperinsulinism by activating glucagon receptors and promoting glucose production in the liver. ^{1 2 3 4 5}

Is HM15136 safe for humans?

The safety data for HM15136, also known as Efpegerglucagon or LAPSGlucagon Analog, is limited to preclinical studies in animals, which showed it was more soluble and had a longer duration of action than natural glucagon. However, there is no specific safety data available for humans in the provided research articles. ^{1 2 6 7 8}

How does the drug HM15136 differ from other treatments for congenital hyperinsulinism?

HM15136 is a novel long-acting glucagon analog designed to address the limitations of natural glucagon, such as poor solubility and short duration of action. It is more soluble and has a longer half-life, making it potentially more effective in managing congenital hyperinsulinism compared to existing treatments. ^{1 2 3 6 7}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• HM15136 (GLP-1 Receptor Agonist)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Dasiglucagon for the treatment of congenital hyperinsulinism: a randomised phase 3 trial in infants and children. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A selective nonpeptide somatostatin receptor 5 agonist effectively decreases insulin secretion in hyperinsulinism. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. [2022]

5. Poland pubmed.ncbi.nlm.nih.gov

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management? [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Optimization of a Glucagon-Like Peptide 1 Receptor Antagonist Antibody for Treatment of Hyperinsulinism. [2023]

7. United States 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

The Use of Lanreotide in the Treatment of Congenital Hyperinsulinism. [2022]