cPKU Olan Yetişkin Bireylerde NGGT002'nin Güvenlilik ve Etkinlik Çalışması

Sade dilde özet

Bu çalışma, klasik fenilketonüri (classical phenylketonuria, cPKU) olan yetişkinlerde NGGT002 gen terapisinin güvenliliğini ve etkinliğini incelemektedir; bu hastalık PAH genindeki değişikliklerden kaynaklanır. PAH geninde iki alelli patojenik varyant taşıyan, 18-55 yaş arası ve yüksek kan Phe düzeyleri olan hastalar dahil edilebilmektedir. Çalışma Faz 1/Faz 2 aşamasında yürütülmekte ve halen katılımcı almaktadır.

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

Deney bilgileri

Faz

PHASE1/PHASE2

Durum

Katılımcı alıyor

Sponsor

NGGT (Suzhou) Biotechnology Co., Ltd.

Müdahale

NGGT002

Başlangıç

25.07.2024

Tahmini bitiş

30.07.2031

Ülkeler

China

İlgili genler

Merkezler

• Bengbu, China
• Shanghai, China

Uygunluk kriterleri

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

Inclusion Criteria:

1. Voluntarily participating in the study and signing the informed consent form;
2. Gender is not limited; patients must carry biallelic pathogenic or likely pathogenic variants in the PAH gene;
3. Adult patients aged 18 to 55 years;
4. In the past 24 months, at least two blood Phe concentrations have been ≥600 μmol/L (10 mg/dL), with at least one of these measurements taken within 6 months prior to the screening period;
5. Willing and able to manage their diet;
6. According to the investigator's opinion, willing and able to comply with the study procedures and requirements;
7. Women of childbearing potential must have a negative serum HCG test within 7 days before dosing. Participants must agree to use highly effective contraceptive measures for at least one year after receiving NGGT002.

Exclusion Criteria:

1. Presence of anti-AAV8 neutralizing antibodies（≥1:5）
2. Subjects whose disease is well-controlled with existing therapies, such as those currently receiving medications like Sapropterin Dihydrochloride tablets, Pegvaliase-pqpz, etc.;
3. Before dosing, the patient's hematological laboratory tests exceed any of the following limits:

   * Alanine Transaminase (ALT) \> 1.5×ULN and/or Aspartate Aminotransferase (AST) \> 1.5×ULN
   * Alkaline Phosphatase (ALP) \> 1.5×ULN
   * Total Bilirubin (TBil) \> 1.5×ULN, Direct Bilirubin \> 1.5×ULN
   * International Normalized Ratio (INR) \> 1.5
   * Serum Creatinine (Scr) \> 1.5×ULN
   * Hematological values outside the normal range (Hemoglobin: \<110 g/L for males, \<100 g/L for females, White Blood Cells \<3.0×10\^9/L, Neutrophils \<1.5×10\^9/L, Platelets \<100×10\^9/L)
   * Glycated Hemoglobin (HbA1c) \> 6% or Fasting Blood Glucose \> 6.1 mmol/L
4. At screening, clinically significant abnormal vital signs, physical examination, laboratory test results, or other relevant findings that, in the investigator's opinion, make the subject unsuitable for inclusion;
5. In the investigator's assessment, the subject has contraindications to corticosteroid use or conditions that could lead to a worsening of the condition;
6. Hepatitis A virus infection, active or occult hepatitis B virus infection, active hepatitis C virus infection, positive for Human Immunodeficiency Virus (HIV) antibodies, positive syphilis test, active or latent tuberculosis (TB) infection;
7. A significant history of liver disease, such as steatosis, fibrosis, non-alcoholic steatohepatitis, and cirrhosis, biliary diseases, within 6 months prior to signing the informed consent form, except for Gilbert's syndrome;
8. History of malignant tumors;
9. Imaging (liver ultrasound) evidence of severe liver diseases such as hepatic fibrosis or cirrhosis;
10. In the investigator's assessment, the subject has a history of serious cardiovascular, respiratory, gastrointestinal, endocrine, renal, hematological, neurological, psychiatric, or other systemic diseases before screening;
11. History of allergy to human serum albumin;
12. Subjects with a history of substance abuse (e.g., alcohol, heroin, amphetamines, etc.);
13. Subjects who have received gene therapy at any time in the past.
14. Subjects who have participated in other non-gene therapy drug clinical trials and received the investigational drug within 3 months (or 5 half-lives of the other investigational drug) prior to screening;
15. Subjects with elevated Alpha-fetoprotein (AFP);
16. Other conditions that, in the investigator's opinion, make the subject unsuitable for inclusion, such as severe comorbidities associated with PKU (e.g., renal insufficiency or renal failure, osteoporosis, anemia, gastroesophageal reflux or peptic ulcer, major depressive disorder, epilepsy, etc.);
17. Subjects weighing more than 100 kg;
18. Subjects whose daily diet includes excessive natural protein intake (\>2 g/kg/day).