NL-OMON54405招募中2 期
Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults with Hereditary Angioedema (HAE) - NTLA-2002 in Adults with Hereditary Angioedema (HAE)
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 4
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
- 年龄范围
- 18 至 99（—）
入选标准
- •Prospective approval of protocol deviations to recruitment and enrollment
- •criteria, also known as protocol waivers or exemptions, are not permitted.
- •Participants are eligible to be included in the study only if all of the
- •following criteria apply:
- •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
- •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
- •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
- •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
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •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
- •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
- •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
- 另有 2 项未显示
研究者
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