Efpegerglucagon for Congenital hyperinsulinism (CHI)

Inclusion criteria

• {"criterion_text":"- Male and female subjects with CHI and persistent hypoglycemia defined as experiencing ≥3 level 1 or level 2 hypoglycemia events per week (blood glucose <70 mg/dL [<3.9 mmol/L]) despite current SoC treatment according to the investigator's evaluation or documentation\n- Stable therapy with SoC medications or documented to be nonresponsive to 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\n- 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\n- HbA1c <7%\n- 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.\n- 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 one parent has legal responsibility for the care and custody of the child\n- Criteria for Optional Extension Treatment Period: If the subject has not experienced any clinically significant AEs in the opinion of the investigator and sponsor during the 8-week core treatment period, the subject will be given an opportunity to participate in the optional extension treatment period."}

Exclusion criteria

• {"criterion_text":"- With type 1 / type 2 diabetes mellitus\n- History of any serious adverse reaction or hypersensitivity to study drug components\n- Anemia findings of hemoglobin <10 g/dL in clinical laboratory results at sc\n- 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).\n- History of any clinically significant hepatic findings including gallstones (including incidental finding by ultrasonography or other imaging modalities)\n- Hypertension or hypotension not on stable dose of supportive medication for at least 3 M prior to Scr\n- 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\n- History of any active infection, other than mild viral illness within 30D prior to dosing as judged by investigator\n- History of/ positive test for hepatitis B surface antigen, hepatitis C virus antibody, or HIV type 1 or type 2 antibody at sc\n- Any anticipated procedures (eg surgery) that might interfere with compliance or completion of trial\n- Presence of clinically significant physical examination, ECG, or clinical laboratory finding at sc that in opinion of investigator, may interfere with any aspect of study conduct / interpretation of results\n- Other reasons for hypoglycemia, including but not limited to druginduced 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\n- Pregnant female subjects based on sc and baseline pregnancy tests\n- With history of major depression, anxiety, or other psychiatric disorders (within last 6 M), requiring active and ongoing medication regimen adjustments including selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, antipsychotics, or lithium.\n- Baseline period exclusion criteria include following: - Use of glucagon within 24 hours before 1st HM15136 administration - Significant changes to CHI medications during sc - Less than 3 hypoglycemia events/ W before baseline period\n- Criteria for Optional Extension Treatment Period: if subject experiences clinically significant AEs with HM15136 treatment where the risks outweigh expected benefits or has other new complications that in the opinion of the investigator and/or sponsor would preclude continued participation, not be allowed to participate in optional extension treatment period.\n- 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)\n- 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.\n- Unable to tolerate adhesive tape or has any unresolved adverse skin reaction in area of CGMS sensor placement\n- 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)\n- Consumption of alcohol in subj. <18 to 21 y. and heavy drinking in older adults\n- 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\n- History of any major surgery within 6 M prior to sc (except for pancreatectomy)"}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability endpoints: 1. Incidence of adverse event (AE), treatment-emergent AE (TEAE), and serious AE (SAE) for the following: ° level of severity ° related to/not related to study drug ° leading to discontinuation of study drug ° AE of special interest ° death","definition_or_measurement_approach":"Incidence and classification of AEs, TEAEs, SAEs; severity, relationship to study drug, discontinuations, AEs of special interest, death as recorded during study."}
• {"endpoint_text":"- 2. Incidence of clinical laboratory abnormalities","definition_or_measurement_approach":"Clinical laboratory test results compared to baseline; incidence of abnormalities recorded."}
• {"endpoint_text":"- 3. Immunogenicity","definition_or_measurement_approach":"Assessment of anti-drug antibodies/immunogenic response (no further detail in dataset)."}
• {"endpoint_text":"- 4. Incidence and severity of clinical findings on physical examination","definition_or_measurement_approach":"Physical exam findings assessed for incidence and severity versus baseline."}
• {"endpoint_text":"- 5. Change from baseline in vital signs (blood pressure, heart rate, respiratory rate, and body temperature)","definition_or_measurement_approach":"Vital signs measured and change from baseline recorded."}
• {"endpoint_text":"- 6. Change from baseline in 12-lead ECG parameters; the primary ECG endpoint will be QT interval corrected for heart rate using Fridericia's formula (QTcF)","definition_or_measurement_approach":"12-lead ECG measurements with QTc corrected using Fridericia's formula (QTcF) as primary ECG endpoint."}
• {"endpoint_text":"- Pharmacokinetic endpoints: 1. Maximum concentration (Cmax)","definition_or_measurement_approach":"Serum pharmacokinetic sampling to determine Cmax."}
• {"endpoint_text":"- 2. Time to reach Cmax (tmax)","definition_or_measurement_approach":"PK sampling to determine tmax."}
• {"endpoint_text":"- 3. Trough serum concentration (Ctrough)","definition_or_measurement_approach":"PK sampling to measure trough concentrations at steady state."}
• {"endpoint_text":"- 4. Area under the concentration-time curve (AUC), eg, AUC from time 0 to time t (AUC0-t) at steady state during the period of injection","definition_or_measurement_approach":"Calculation of AUC0-t from PK concentration-time data at steady state."}
• {"endpoint_text":"- 5. Terminal elimination rate constant (kel)","definition_or_measurement_approach":"PK analysis to estimate terminal elimination rate constant."}
• {"endpoint_text":"- 6. Terminal half-life (t1/2)","definition_or_measurement_approach":"PK analysis to estimate terminal half-life."}
• {"endpoint_text":"- 7. Apparent clearance at steady state (CLss/F)","definition_or_measurement_approach":"PK parameter estimation for clearance at steady state."}
• {"endpoint_text":"- 8. Apparent volume of distribution at steady state during the terminal phase (Vss/F)","definition_or_measurement_approach":"PK parameter estimation for volume of distribution at steady state."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in average weekly number and rate of level 1 or level 2 hypoglycemia events at Week 8 (Day 50 to Day 56) by the 7-point SMBG ° level 1 or level 2 hypoglycemia event: glucose <70 mg/dL (<3.9 mmol/L)","definition_or_measurement_approach":"Change from baseline in weekly number/rate of hypoglycemia events measured by 7-point self-monitored blood glucose (SMBG); level 1/2 defined as glucose <70 mg/dL (<3.9 mmol/L)."}
• {"endpoint_text":"- Change from baseline in weekly rate of level 1 or level 2 hypoglycemia events in Diary ° level 1 or level 2 hypoglycemia event: glucose <70 mg/dL (<3.9 mmol/L) 44-week Optional Extension Treatment Period","definition_or_measurement_approach":"Diary-recorded weekly rate of hypoglycemia events during optional extension; level 1/2 defined as glucose <70 mg/dL (<3.9 mmol/L)."}
• {"endpoint_text":"- Incidence of AE, TEAE, and SAE for the following: ° level of severity ° related to/not related to study drug ° leading to discontinuation of study drug ° AESIs ° death","definition_or_measurement_approach":"Incidence and classification of safety events as recorded."}
• {"endpoint_text":"- Incidence of clinical laboratory abnormalities","definition_or_measurement_approach":"Laboratory results compared to baseline; incidence recorded."}
• {"endpoint_text":"- Immunogenicity","definition_or_measurement_approach":"Assessment of immunogenic response (anti-drug antibodies) during study."}
• {"endpoint_text":"- Incidence and severity of clinical findings on physical examination","definition_or_measurement_approach":"Physical exams assessed for incidence and severity."}
• {"endpoint_text":"- Change from baseline in vital signs (BP, HR, respiratory rate, and body temperature)","definition_or_measurement_approach":"Measurement of vital signs and comparison to baseline."}
• {"endpoint_text":"- Change from baseline in 12-lead ECG parameters; the primary ECG endpoint will be QTcF","definition_or_measurement_approach":"12-lead ECG parameter changes with QTcF as primary ECG metric."}

Germany

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

701

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Hanmi Pharm. Co. Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Korea, Republic of

Contract research organisations

Name

Fortrea Inc.

Responsibilities

codes:1,10,11,12,2,5,6,8

Name

Bioclinica Inc.

Responsibilities

ECG (sponsorDuties code 15)

Name

Q Squared Solutions LLC

Responsibilities

Pharmacodynamic samples (sponsorDuties code 15)

Name

Labcorp Central Laboratory Services SARL

Responsibilities

code:4

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"codes:1,10,11,12,2,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"15 (ECG)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"15 (Pharmacodynamic samples)","organisation_type":"Laboratory/Research/Testing facility"}