A study to Evaluate the Safety, the Tolerability, the Pharmacokinetics and the Efficacy of HM15136 administered in pediatric Patients with Congenital Hyperinsulinism (CHI)
- Conditions
- Congenital Hyperinsulinism (CHI)MedDRA version: 20.0Level: PTClassification code 10061211Term: HyperinsulinismSystem Organ Class: 10027433 - Metabolism and nutrition disordersMedDRA version: 23.0Level: LLTClassification code 10083499Term: Congenital hyperinsulinemic hypoglycemiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2021-000508-39-DE
- Lead Sponsor
- Hanmi Pharm. Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
Subjects who meet all of the following criteria at screening will be eligible to participate in the clinical study.
Note: Subjects not eligible because of laboratory result(s) may have the laboratory test(s) (hematology, clinical chemistry including liver function tests, hemoglobin A1c [HbA1c], and electrocardiogram [ECG]) repeated once during the screening period at the discretion of the investigator to determine eligibility.
Inclusion Criteria
1. Cohort 1 (0.04 mg/kg): Male and female subjects aged =2 years (applicable to the US) and male and female subjects aged =12 years
(applicable to Germany, UK, and Israel); Cohort 2 (0.06 mg/kg): Male and female subjects aged =2 years in all countries.
2. Stable therapy with SoC medications with or without nutritional supplementation (nutritional supplementation includes enteral feeding such as gastric carbohydrates [administered orally, via nasogastric tube, or gastrostomy]) as described below:
a) Subjects aged =12 years on stable therapy with diazoxide or somatostatin analog (ie, octreotide and lanreotide) for at least 3 months prior to screening Note: Subjects treated with octreotide infusion could be included after review by the investigator and medical monitor.
b) Children aged 2 to 11 years on stable therapy with diazoxide or octreotide for at least 1 month prior to screening; if on lanreotide, stability should be for at least 3 months prior to screening
c) Subjects receiving other medications such as sirolimus or nifedipine could be included after review by the investigator and medical monitor
3. Subjects on long-acting somatostatin analog may be enrolled in the study if they have been on stable monthly (every 4 weeks) injections for at least 3 months before screening. Subjects would be required to synchronize their monthly somatostatin analog injection with the first and fifth injection of HM15136 (first dosing date = long-acting somatostatin injection date). Note: Lanreotide users not on every 4 weeks dosing regimen could be enrolled after discussion with the investigator and medical monitor
4. HbA1c <7%
5. Female subjects of childbearing potential must be nonpregnant and nonlactating. All females (regardless of age) of childbearing potential must have a negative urine/serum pregnancy test and must use highly effective methods of contraception throughout the duration of the study and until 60 days after final dose of HM15136 administration. Male subjects must agree to use condoms as a contraceptive measure throughout the duration of the study and until 60 days after final dose of HM15136 administration.
6. Following receipt of oral and written information about the trial, the subject (children) (depending on local Institutional Review Board/Independent Ethics Committee requirements, or local regulatory requirements) must provide an assent and one or both parents (a) or guardians of the subject must provide signed informed consent before any trial-related activity is carried out. Adult subjects must provide signed informed consent. Adult subjects unable to provide informed consent and who require his/her legally authorized representative to provide informed consent will not be enrolled in the study.
(a) If required by local regulations, both parents must give their permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child
Are the trial subjects under 18? yes
Number o
1.with type 1 / type 2 diabetes mellitus
2. Other reasons for hypoglycemia, including but not limited to drug-induced hyperinsulinemic hypoglycemia, exogenous insulin-induced hypoglycemia, insulinoma, insulin resistance syndrome, nonislet cells tumor hypoglycemia, postgastric bypass, postfundoplication for gastroesophageal reflux, or dumping syndrome with postprandial hypoglycemia, or hypoglycemia due to other endocrine or inherited metabolic diseases
3. Treatment of CHI with continuous intravenous glucose or glucagon infusion (requiring hospitalization of >1 W) within 1 M prior to screening (sc) (subj. treated with a transient intravenous glucose or glucagon infusion could be included after review by investigator & medical monitor)
4. History of or current active disease of any clinically-significant surgical, medical, or psychiatric condition that, in judgment of investigator, might interfere with absorption, distribution/ metabolism of study drug, interpretation of study assessments/ pose an additional safety risk in administering study drug to subj.
5. unable to tolerate adhesive tape or has any unresolved adverse skin reaction in area of CGMS sensor placement
6. with current use of any drugs known to interfere with study drug, glucose metabolism/ study procedures (eg, use of systemic glucocorticoids [exclude. topical, intra-articular or ophthalmic application, nasal spray, or inhaled forms] for >10 consecutive days within 3 M prior to Sc / insulin)
7. Consumption of alcohol in subj. <18 to 21 y. and heavy drinking in older adults
8. Has participated in an interventional clinical trial (investigational or marketed product) within1 M of Sc or 5 half-lives of drug under investigation (whichever comes first)/ plans to participate in another interventional CT
9. History of any major surgery within 6 M prior to sc (except for pancreatectomy)
10. History of any serious adverse reaction or hypersensitivity to study drug components
11. Anemia findings of hemoglobin <10 g/dL in clinical laboratory results at sc
12. Abnormal clinical laboratory results at sc:
a) History of renal disease/ abnormal kidney function tests at sc: estimated glomerular filtration rate <60 mL/min/1.73m2 as estimated using pediatric formula (Schwartz formula) for subj. <18 y. and chronic kidney disease epidemiology collaboration formula for subj. =18 y.
b) Clinically significant thyroid function abnormality in opinion of investigator. If sc thyroid stimulating hormone is >1.5 x ULN or <0.4 mIU/L, reflex laboratory testing for T3 and free T4 will be performed
c) Clinically significant abnormal hepatic function tests suggestive of hepatic impairment: alanine aminotransferase and/or aspartate aminotransferase >3 x ULN or total bilirubin >1.5 x ULN (unless due to Gilbert’s syndrome, total bilirubin >3.0 x ULN and direct bilirubin >1.5 x ULN).
13. History of any clinically significant hepatic findings including gallstones (including incidental finding by ultrasonography or other imaging modalities)
14. Hypertension or hypotension not on stable dose of supportive medication for at least 3 M prior to Scr
15. Any clinically significant abnormality at sc identified on ECG that in opinion of investigator would affect subject’s ability to participate in trial or cardiac arrhythmia requiring medical or surgical treatment within 6 M prior to sc
16. History of any active infection, other than mild viral illness within 30D prior to dosing as judged by investigator
17. History of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method