EUCTR2021-001693-33-ES进行中（未招募）1 期
Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults with Hereditary Angioedema (HAE)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Subjects = 18 years of age at the time of signing the informed consent.
- •2. Documented diagnosis of HAE (Type I or II) confirmed by laboratory assessment of functional C1-INH level and C1-INH concentration:
- •a. For HAE Type I: Both functional C1-INH level AND C1-INH concentration should be <50% of normal limits (or per local standard)
- •b. For HAE Type II: Functional C1-INH level should be <50% of normal limits (or per local standard). C1-INH concentration may be normal or
- •above normal.
- •C1-INH testing during screening, at either the central or an accredited local laboratory, or previously documented results from an accredited
- •local laboratory may be used to confirm eligibility. If frequent use of C1- INH for the prevention or treatment of HAE attacks would confound
- •interpretation of C1-INH testing, genetic testing for known variants in the SERPING1 gene in a local laboratory may be used to confirm
- •eligibility upon consultation with the Sponsor.
- •3. Investigator-confirmed attacks (per Appendix 3 in Section 10.3):
- •a. Phase 1 only: Subjects must have an Investigator-confirmed and documented historical HAE attack number of at least 3 during the
- •previous 3 months (90 days) from the start of screening.
- •b. Phase 2 only: Subjects must have an Investigator-confirmed and documented historical HAE attack number of at least 3 during the
- •previous 3 months (90 days) to enter the Screening/Run-In period and an Investigator-confirmed and documented HAE attacks number of at
- •least 2 during the up to 8-week (up to 56-day) Screening/Run-In period (or at least 3 to be eligible for early enrollment and randomization).
- •c. Netherlands only: For both Phase 1 and Phase 2, subjects must have had inadequate control of HAE attacks, as determined by the
- •Investigator, while receiving at least one prior prophylactic regimen, or have required discontinuation from, or otherwise be ineligible for,
- •available prophylactic agents.
- •4. Phase 2 only: Subjects must agree to refrain from the use of prophylactic therapies from within 5 half-lives prior to the start of the
- •Screening/Run-In period through the end of the 16-week primary observation period, and the Investigator must confirm that this is
- •medically appropriate and does not place the subject at undue safety risk. See Section 10.2 for a list of prophylaxis agents, half-lives, and
- •recommended wash-out period.
- •5. Subjects must have access to, and the ability to use, = 1 acute medication(s) to treat angioedema attacks.
- •6. Subjects must meet the following laboratory criteria during Screening:
- •a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (see exception for Gilbert's Syndrome below) = upper
- •limit of normal (ULN) range at Screening.
- •b. For subjects with a history of Gilbert's Syndrome, total bilirubin = 2 × ULN on screening evaluation.
- •c. Serum creatinine is = ULN, or, for subjects in whom serum creatinine is above the ULN, they can be included if the estimated glomerular
- •filtration rate (eGFR) is > 60 mL/min/1.73 m2 as measured by the Modification of Diet in Renal Disease equation at Screening.
- •d. Platelet count = 100,000 cells/mm3 at Screening.
- •e. Within reference range or Principal Investigator (PI)-determined clinically non-significant activated partial thromboplastin time (aPTT),
- •international normalized ratio (INR), fibrinogen and d-dimer levels at Screening.
- •7. Male subjects with partners of childbearing potential must agree to using a condom as of the date of informed consent an
排除标准
- •1. Use of ecallantide from 1 week prior to the start of Screening through the 16-week primary observation period.
- •2. Use of C1 esterase inhibitor (C1-INH) for HAE within 5 half-lives of the agent before initiation of the Phase 2 Screening/Run-In period, i.e., 24-
- •hour washout is required before starting the Screening/Run-In period after the use of rabbit purified C1-INH (ruconest), and 4-day washout is
- •required before starting the Screening/Run-In period after the use of human plasma purified C1-INH (berinert). Note: during the
- •Screening/Run-In period, C1-INH may be used to treat an acute HAE attack.
- •3. Concurrent diagnosis of any other type of recurrent angioedema, including acquired or idiopathic angioedema.
- •4. Subjects who have known hypersensitivity to any lipid nanoparticles (LNP) component (or its excipients) or who have previously received
- •LNP and experienced any treatment-related clinically significant laboratory abnormalities or AEs listed below:
- •a. ALT or AST > 3 × ULN if baseline was normal or > 3 × baseline if baseline was above normal.
- •b. INR, aPTT or d-dimer > 1.5 × ULN if baseline was normal or > 1.5 × baseline if baseline was above normal.
- •c. Any LNP treatment-related AEs classified as CTCAE Grade 3 or higher.
- •d. Infusion-related reaction (IRR) to an LNP-containing product (or excipients) requiring treatment or discontinuation of infusion; NOTE:
- •slowing of the infusion rate to mitigate an IRR is not considered exclusionary.
- •e. Any LNP treatment-related AEs which in the opinion of the Investigator should be exclusionary.
- •5. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 90
- •days prior to study drug administration.
- •6. Unable or unwilling to take the required pre-treatment medication regimen.
- •7. Female subjects of childbearing potential are excluded from the study if they:
- •a. are breastfeeding or plan to breastfeed during treatment and for an additional 12 months after the last study drug administration.
- •b. have a positive pregnancy test at screening and/or Day 1.
- •8. Antithrombotic therapy other than aspirin (e.g., warfarin, dabigatran, apixaban) within 14 days prior to study drug administration.
- •9. History of thrombophilia, or positive genetic test for Factor V Leiden and/or prothrombin 20210.
- •10. History of cirrhosis.
- •11. Known or suspected systemic viral, parasitic, or fungal infection including coronavirus disease (COVID-19) or received antibiotics for
- •bacterial infection within 14 days prior to Screening.
- •12. History of Hepatitis B or C infection or positive Hepatitis B surface antigen (HbsAg) or Hepatitis C virus antibody (HCVAb) test at Screening.
- •13. History of positive human immunodeficiency virus (HIV) status.
- •14. Prior liver, heart, or other solid organ transplant or bone marrow transplant or anticipated transplant within 1 year of Screening. Note: prior history of or planned corneal transplant is not exclusionary.
- •15. Subject has a history of alcohol or drug abuse within 3 years prior to Screening.
- •16. Any condition, laboratory abnormality, psycho-social stressor, pattern of behavior, or other reason that, in the Investigator's opinion,
- •could adversely affect the safety of the subject, impair the assessment of study results, or preclude compliance with the study.
- •17. Unwilling to comply with study procedures including follow-up as specified by the protocol or unwilling to cooperate fully with the
- •Investigator.
研究者
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