EUCTR2021-005733-16-PT进行中（未招募）1 期
A Phase 1/2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Single Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia Followed by an Open-Label Extension - Part B, C of first in human study of DNL593 in FTD patients
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
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.Aged = 18 to = 80 years
- •2.Have a BMI of = 18 to = 32 kg/m2
- •3.Are willing and able to give informed consent for study participation or have a care partner or LAR who is willing and
- •able to provide consent
- •4.Have a study partner who is able to reliably complete the CDR plus NACC FTLD with participant and will accompany
- •the participant to study visits or be available by telephone at designated times. Study partner must have frequent
- •contact with participant (> 10 hours per week) and be able to reasonably participate in all CDR plus NACC FTLD
- •assessments in the study period.
- •Note: A second study partner may serve as backup, but it is preferred that one study partner be primarily responsible
- •for the CDR plus NACC FTLD assessments.
- •5.Are able to communicate with the investigator and staff either independently or through a caregiver
- •6.Are willing and able to comply with the requirements of the study, including scheduled visits, study restrictions,
- •laboratory tests, and all other study procedures. In the investigator’s opinion, both participant and caregiver are able to
- •complete all required study procedures and visits during the Part B period of 24 weeks.
- •7.Women of non-childbearing potential, defined as must have been surgically sterilized (hysterectomy, bilateral
- •oophorectomy/salpingectomy, or bilateral tubal ligation; proper documentation required) > 3 months prior to dosing
- •(Essure fallopian tube coil placement is not accepted as surgical sterilization because of the high failure rate), or be
- •postmenopausal (amenorrheic for > 12 consecutive months before dosing, with a FSH level of > 40 IU/L at screening).
- •Women who are of childbearing potential but on highly effective, low user dependent contraceptive methods will be
- •8.For men: When engaging in sex with a WOCBP, both the male participant and his female partner must use highly
- •effective contraception consisting of two forms of birth control, one of which must be a male barrier method (such as a
- •latex or polyurethane condom), from the start of dosing, throughout the study period, and for 90 days after the final
- •administration of study intervention.
- •9.For men: The participant must not donate sperm at any time from the start of dosing, throughout the study period,
- •and for 90 days after the final administration of study intervention.
- •10.Have a diagnosis of FTD, including the probable bvFTD or PPA. Other diagnosis related to FTD syndrome,
- •including, but not limited to, CBS or progressive supranuclear palsy (PSP) syndrome, are allowed pending Sponsor
- •and investigator agreement.
- •11.Have a CDR plus NACC FTLD global score = 0.5
- •12.Have confirmed GRN mutation via genetic testing or historical records available for review by investigator
- •13.Doses of other chronic prescription medications that may affect cognition or behaviour at the determination of the
- •investigator must be stable for = 1 month prior to screening; participant is expected to stay on a stable regimen
- •throughout the study. Participants who initiated or changed medication (described above) doses within 1 month prior
- •to screening may be rescreened after dose stabilization.
- •Participants from Part B who complete the double-blind period through the SFU visit are eligible to enter the 18-month
- •Part C OLE, at the discretion of the investigator and Sponsor. Each participant will be reconsented for the OLE.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
排除标准
- •1.Have any history of unstable or poorly controlled psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal,
- •hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders. Well
- •controlled conditions are permitted if investigator and Sponsor agree.
- •2.Have a history of malignancy within 5 years before screening, except fully resected basal cell carcinoma or other
- •malignancies (such as prostate cancer) at low risk of recurrence, depending on investigator and medical monitor
- •3.Have a history of clinically significant neurologic disorders other than FTD (for Part B only), including stroke, cognitive
- •impairment due to causes other than FTD, or seizure within 5 years of screening, or head trauma with loss of
- •consciousness within 2 years of screening. Note: Single incidence of provoked seizure with a clear cause may be
- •acceptable with Investigator and Sponsor approval.
- •4.Have the presence of any contraindication to MRI of the brain
- •5.Have a current significant psychiatric disorder, suicidal ideation in the previous 6 months as assessed by the
- •Baseline/Screening version of the C-SSRS (for Part B only)
- •6.Have evidence of hepatic impairment, including ALT or AST > 2 × ULN or bilirubin> 1.5 × ULN at screening or
- •7.Have a history of clinically significant renal impairment or an eGFR < 45 mL/min/1.73 m2 at screening
- •8.Have a history or presence of a clinically significant ECG abnormality
- •9.Have donated or lost > 500 mL whole blood within 30 days before entry in the treatment period
- •10.Received vaccination (including second dose or any booster shots) against SARS-CoV-2 within 4 weeks of the start
- •11.Have any other issue that, in the opinion of the investigator, would make the participant ineligible for study
- •participation
- •For full exclusion criterion for Part B, please refer to Section 5.1.2.2 of the protocol.
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