Homozigot Ailesel Hiperkolesterolemide NGGT006 Gen Terapisi

Sade dilde özet

Bu çalışma, homozigot ailesel hiperkolesterolemi tanılı hastalarda NGGT006 adlı gen terapisini incelemektedir. Çalışmaya, LDL reseptörü (LDLR) geninde iki mutant alel taşıdığı genetik olarak doğrulanmış, 12-55 yaş arası hastalar alınmaktadır (ilk hastanın 18 yaş ve üzeri olması gerekmektedir). Erken Faz 1 aşamasında yürütülmekte ve katılımcı almaktadır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Erken Faz 1 (Early Phase 1)

Durum

Katılımcı alıyor

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Müdahale

NGGT006

Başlangıç

29.10.2023

Tahmini bitiş

01.11.2028

Ülkeler

China

İlgili genler

Merkezler

• Xi'an, China

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

Inclusion Criteria:

* Voluntarily sign informed consent form;
* Male or female, 12 ≤ age ≤ 55 years (first patient≥ 18 years), diagnosed as homozygous familial hypercholesterolemia with genetic confirmation of two mutant alleles of the LDL receptor (LDLR) gene;
* AAV8 neutralizing antibodies can be negative or reduced to negative levels through methods such as plasma exchange.
* Untreated LDL-C ≥10 mmol/L (386mg/ dL) or treated LDL-C ≥7 mmol/L (270mg/ dL) together with cutaneous or tendon xanthoma before age 18 years;
* Had been on stable medication for ≥30 days if receiving lipid-lowering therapy (or ≥60 days if receiving alirocumab or evolocumab) prior to screening and not scheduled for addition of new drugs or dose adjustments during the study;
* Agreed to follow a low-fat diet and comply with all study procedures;
* Agreed to maintain a similar exercise volume and intensity to baseline during the study period;
* Agreed to maintain good lifestyle habits;
* No history of alcohol abuse or alcohol dependence (diagnosed as F10 in ICD-10 code);
* No sexual activity for 14 days prior to administration and negative serum pregnancy test in female participants;
* Participants of childbearing potential agreed to use highly effective contraception for at least 365 days from administration of NGGT006;
* No plan of stent implantation within 3 months.

Exclusion Criteria:

* Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV) or syphilis test;
* Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) ≥2 × ULN;
* Baseline blood pressure ≥160/100 mmHg (1 repeat measurement is allowed);
* Uncontrolled myocardial infarction or heart failure, or had surgery plan within 1 year;
* Diabetes diagnosed within 3 months or with poor control (HbA1c ≥9%);
* Acute or chronic kidney failure;
* Hemoglobin (Hb) ≥120g/L (male), Hb ≥110 (female);
* Abnormal platelet counts or morphology;
* History or laboratory tests suggestive of thrombosis;
* Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia, active peptic ulcer);
* Life expectancy less than 1 year;
* With malignant tumors;
* Liver fibrosis or liver cancer;
* Previous gene therapy treatment;
* Hypersensitivity to AAV or cortisone or immunosuppressants (sirolimus, rituximab, tacrolimus);
* Participation in any other clinical trial within 3 months;
* History of stent implantation within 1 month or myocardial infarction within 3 months;
* Breastfeeding females;
* Any other condition that may not be appropriate for the study in the opinion of the Investigator.