A24110He in a placebo-controlled trial evaluating safety in subjects with elevated plasma triglycerides

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lipigon Pharmaceuticals AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Feb 2024 → 8 Jan 2026

Decision date (initial)

2024-02-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Safety, Pharmacodynamic

To evaluate the safety and local tolerability of A24110He in a multiple dose trial in subjects with elevated plasma triglyceride concentrations

Secondary objectives 2

1. To evaluate the exposure of A24110He in multiple dose regimen in subjects with and elevated plasma triglyceride concentrations
2. To characterise the pharmacodynamic profile of A24110He in multiple dose regimen in subjects with elevated plasma triglyceride concentrations

Conditions and MedDRA coding

Moderate to severe hypertriglyceridemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provision of signed and dated, written informed consent prior to any trial specific procedures.
2. Access to proper venous access as per Investigator discretion.
3. Willing to comply with CTP procedures and restrictions.
4. Age 18-78 years (both inclusive).
5. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and must be using a highly effective contraceptive method. All details that need to be applied are noted in the main body text of the CTP. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Male subjects who are sexually active and not surgically sterile must have undergone a vasectomy or be willing to use condom or practice sexual abstinence (only allowed when this is the preferred and usual lifestyle of the subject) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 6 months after last dosing with A24110He. Their female partner of childbearing potential must use contraception methods with a failure rate of < 1% to prevent pregnancy during the trial and until 180 days after the last dose of A24110He.
6. Body mass index (BMI) <38 kg/m2. Body weight ≥ 56 kg.
7. History of hypertriglyceridemia prior to screening. Any lipid-lowering therapy must have been stable for at least 1 month prior to screening (visit 1) and be kept stable until randomisation (visit 4). Stable treatment is defined as unchanged in terms of dose and compound. Change of product is allowed if active substance is the same.
8. Fasting TGpl levels ≥ 1.7 mmol/L at Visit 1.
9. Subjects with type 2 diabetes mellitus must be on stable glucose-lowering treatment (metformin, sulfonylurea, glitazones, DPP4-inhibitors, GLP-1 agonists, SGLT2-inhibitors, repaglinide) for 3 months prior to screening (visit 1) and be kept stable until randomisation (Visit 4). Stable treatment is defined as unchanged in terms of dose and compound. Change of product is allowed if active substance is the same. The subject´s glucose control must be acceptable in terms of safety, based on the Investigator´s discretion.

Exclusion criteria 23

1. Unstable body weight, defined as more than 5% self-reported change in body weight in the period from 30 days prior to Visit 1. Intention of losing body weight within 6 months from screening.
2. Current alcohol or drug addiction as judged by the Investigator or high-risk alcohol consumption. High-risk alcohol consumption is defined as more than 14 standard drinks for men and 9 standard drinks for women per week.
3. Overt hypothyroidism, or other conditions potentially affecting plasma triglyceride levels.
4. Any history of acute pancreatitis related to hypertriglyceridaemia (according to investigator judgment) or any other pancreatitis episode during the last 2 years.
5. ASAT, ALAT, ALP or GGT > 2.5 times upper limit of normal (ULN) or bilirubin >1.5 times ULN at Visit 1.
6. S-Creatinine > 1.5 x ULN at Visit 1.
7. HbA1c >70 mmol/mol at Visit 1.
8. Clinically significant disease, or in any other way unsuitable for participation in this trial, which in the opinion of the Investigator might interfere with the interpretation of results and/or safety of the subject.
9. Active inflammatory skin disease or contact dermatitis at Visit 1.
10. Active malignancy within the past 5 years except for in situ removal of basal cell carcinoma or non-melanoma skin cancer.
11. Participation in a clinical trial involving administration of an investigational or a marketed medicine within 3 months or five half-lives of the investigational medicine, whichever is longer, prior to Visit 4.
12. Previous enrolment in the present trial, defined as having participated in any visit beyond Visit 1.
13. Acute coronary syndrome < 3 months prior to Visit 1, stroke < 6 months prior to Visit 1, or symptomatic congestive heart failure.
14. Any significant medical/surgical procedure or trauma within 4 weeks of the first administration of IMP, at the discretion of the Investigator.
15. Any planned major surgery within the duration of the trial.
16. Uncontrolled or previously unknown hypertension; SBP ≥150 mmHg, or DBP ≥95 mmHg. Antihypertensive treatment must have been stable for at least 4 weeks prior to Visit 4.
17. Involved in the planning and/or conduct of the trial.
18. Treatment within 6 months prior to Visit 4 with therapeutic oligonucleotides. mRNA vaccines are allowed.
19. Women who are pregnant, lactating or planning to become pregnant during the trial period, or women of childbearing potential who are not using acceptable contraceptive methods.
20. Treatment with insulin or insulin derivatives during the last 3 months prior to Visit 4.
21. Start of any medication not previously used by the subject within 2 weeks prior to Visit 1.
22. > 1 hypoglycaemic episode during last month prior to Visit 1.
23. Plasma donation within 1 month of Visit 1 or any blood donation or corresponding blood loss during 3 months prior to Visit 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 9

1. Physical examination
2. Assessment of local tolerability
3. Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body temperature
4. 12- lead ECG
5. Safety laboratory tests - Clinical chemistry: creatinine (eGFR), cystatin C (eGFR), ASAT, ALAT, bilirubin, GGT, alkaline phosphatase, albumin, bicarbonate, chloride, phosphate, urea, potassium, calcium, sodium, fasting plasma glucose (FPG), f-insulin, HbA1c, C-reactive protein (CRP), TSH, LDH
6. Safety laboratory tests - Haematology: haemoglobin, EVF, MCV, MHC, MCHC, erythrocyte count, platelet count, leucocyte count with differential count, haptoglobin
7. Safety laboratory tests - Coagulation: APTT, INR
8. Safety laboratory tests - Urinalysis: erythrocytes, glucose, ketones, leucocytes, nitrite, pH, protein, hCG (women of childbearing potential only), albumin, creatinine, urinary albumin/creatinine ratio
9. Frequency, seriousness, intensity of adverse events (AEs)

Secondary endpoints 3

1. Plasma concentrations and PK parameters of A24110He. PK parameters to be determined: a) Maximum plasma concentration (Cmax); b) Time to Cmax (Tmax); c) Terminal half-life (t½) after the fourth dose. Cmax and Tmax will be evaluated in sampling frame up to 4 hours after dosing.
2. Fasting triglyceride levels (clinical routine enzymatic assay)
3. Triglyceride-glucose (TyG) index based on fasting triglyceride and glucose levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lipigon Pharmaceuticals AB

Sponsor organisation

Lipigon Pharmaceuticals AB

Address

Tvistevagen 48 C, Alidhem Alidhem

City

Umea

Postcode

907 36

Country

Sweden

Scientific contact point

Organisation

Lipigon Pharmaceuticals AB

Contact name

Lipigon contact point

Public contact point

Organisation

Lipigon Pharmaceuticals AB

Contact name

Lipigon contact point

Third parties 7

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications