NL-OMON55279撤回3 期
A Phase 3 Global, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of ION-682884 in Patients with Hereditary Transthyretin-Mediated Amyloid Polyneuropathy - NEURO-TTRANSFORM
适应症
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 2
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
- •1. Must have given written informed consent (signed and dated) and any
- •authorizations required by local law and be able to comply with all study
- •requirements
- •2. Aged 18 to 82 years at the time of informed consent
- •3. Satisfy the following:
- •a. Females: must be non-pregnant and non-lactating and either:
- •i. Surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral
- •salpingectomy, bilateral oophorectomy)
- •ii. Post-menopausal (defined as 12 months of spontaneous amenorrhea in females
- •> 55 years of age or, in females * 55 years, 12 months of spontaneous
- •amenorrhea without an alternative medical cause and FSH levels in the
- •postmenopausal range for the laboratory involved)
- •iii. Abstinent* or
- •iv. If engaged in sexual relations of child-bearing potential, agree to use
- •highly effective contraceptive methods (refer to Section 6.3.1) from the time
- •of signing the informed consent form until at least 24 weeks after the last
- •dose of ION*682884 or inotersen and agree to receive a monthly pregnancy test
- •b. Males: Surgically sterile (i.e., bilateral orchidectomy) or, if engaged in
- •sexual relations with a woman of child bearing potential (WOCBP), the patient
- •or the patient*s non-pregnant female partner must use a highly effective
- •contraceptive method (refer to Section 6.3.1) from the time of signing the
- •informed consent form until at least 24 weeks after the last dose of ION*682884
- •or inotersen.
- •* Abstinence (i.e., refraining from heterosexual intercourse throughout the
- •duration of study participation) is only acceptable as true abstinence, i.e.,
- •when this is in line with the preferred and usual lifestyle of the patient.
- •Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation
- •methods), declaration of abstinence for the duration of a trial and withdrawal
- •are not acceptable methods of contraception.
- •4. hATTR-PN as defined by meeting all 3 of the following criteria:
- •a. Stage 1 (ambulatory without assistance) or Stage 2 (ambulatory with
- •assistance) according to the Familial Amyloid Polyneuropathy (FAP) or Coutinho
- •b. Documented genetic mutation in the TTR gene
- •c. Symptoms and signs consistent with neuropathy associated with transthyretin
- •amyloidosis, including NIS * 10 and * 130
- •5. Willingness to adhere to vitamin A supplementation per protocol
排除标准
- •1. Clinically significant abnormalities in medical history (e.g., previous
- •acute coronary syndrome within 6 months of Screening, major surgery within 3
- •months of Screening) or physical examination
- •2. Screening laboratory results as follows, or any other clinically significant
- •abnormalities in screening laboratory values that would render a patient
- •unsuitable for inclusion:
- •a. Urine protein/creatinine ratio (UPCR) * 1000 mg/g. In the event of UPCR
- •above this threshold, eligibility may be confirmed by a repeat random urine
- •test with UPCR < 1000 mg/g or a quantitative total urine protein measurement of
- •< 1000 mg/24 hr
- •b. Renal insufficiency as defined by estimated glomerular filtration rate
- •(eGFRcreat-cys) < 45 mL/min/1.73 m2 at Screening (eGFRcreat-cys is calculated
- •using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]
- •creatinine-cystatin C equation from 2012) (Inker et al. 2012)
- •c. Positive test (including trace) for blood on urinalysis. In the event of a
- •positive test, eligibility may be confirmed with urine microscopy showing * 5
- •red blood cells per high power field
- •d. Alanine aminotransferase/ aspartate aminotransferase (ALT/AST) > 2 × upper
- •limit of normal (ULN)
- •e. Bilirubin * 1.5 × ULN (patients with bilirubin * 1.5 × ULN may be allowed on
- •study if indirect bilirubin only is elevated, ALT/AST is not greater than the
- •ULN and genetic testing confirming Gilbert*s disease)
- •f. Platelets < 125 × 109/L
- •g. HbA1C * 7%
- •h. Abnormal thyroid function tests with clinical significance per Investigator
- •judgement in consultation with the Sponsor Medical Monitor
- •i. Serum vitamin A (or retinol) level at Screening < lower limit of normal
- •(LLN). For patients with a TTR mutation at position 84 (e.g., Ile84Ser or
- •Ile84Asn) and vitamin A < LLN the exclusion criterion is signs or symptoms of
- •vitamin A deficiency (such as dry eye, Bitots* spot observed in the
- •ophthalmology exam, that in the opinion of the ophthalmologist is consistent
- •with vitamin A deficiency)
- •1. Active infection requiring systemic antiviral or antimicrobial therapy that
- •will not be completed prior to Study Day 1
- •2. Unwillingness to comply with study procedures, including follow up, as
- •specified by this protocol, or unwillingness to cooperate fully with the
- •Investigator
- •3. Known history of or positive test for human immunodeficiency virus (HIV),
- •hepatitis C (patients confirmed as cured from previous hepatitis C can be
- •included) or chronic hepatitis B
- •4. Uncontrolled hypertension (BP > 160/100 mm Hg)
- •5. Malignancy within 5 years, except for basal or squamous cell carcinoma of
- •the skin or carcinoma in situ of the cervix that has been successfully
- •treated. Patients with a history of other malignancies that have been treated
- •with curative intent and which have no recurrence within 5 years may also be
- •6. Current treatment with any approved drug for hereditary TTR amyloidosis such
- •as Vyndaqel® / Vyndamax* (tafamidis), Tegsedi* (inotersen), Onpattro*
- •(patisiran), off-label use of diflunisal, doxycycline or tauroursodeoxycholic
- •acid (TUDCA). If previously treated with Vyndaqel® / Vyndamax*, diflunisal or
- •doxycycline, and TUDCA, must have discontinued treatment at least 2 weeks prior
- 另有 2 项未显示
研究者
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