2023-506963-32-00已完成2 期
A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of mRNA 3210 in Participants with Phenylketonuria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 7
- 主要终点
- Number of participants with TEAEs.
研究概览
简要总结
Evaluate the safety and tolerability of multiple doses at escalating dose levels of IV administered mRNA-3210.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomized
- 主要目的
- Follow-up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study if they meet all the following criteria:
- •Signed written informed consent obtained prior to performing any study procedure, including Screening procedures.
- •Age ≥18 to ≤70 years at the time of informed consent.
- •Confirmed diagnosis of PKU due to PAH deficiency by molecular genetic testing from a central lab. Note: Genetic confirmation of PKU due to PAH deficiency can be obtained during the Limited Screening Period as described in Section 4.1.1 of the protocol.
- •At least 3 blood Phe levels ≥600 μmol/L regardless of adherence to a Phe-restricted diet: 2 obtained during the Screening Period (at least 72 hours apart) and at least one historical value 6 to 24 months prior to start of Screening. Note: Blood samples collected to evaluate participants’ Phe levels to determine eligibility should be drawn in the absence of acute illness.
- •Have received documented approval from: a. Study dietitian confirming that participant is willing and able to maintain dietary protein intake consistent with baseline intake during study participation (as described in Section 8.9), AND b. Investigator’s clinical review confirming that diet alone will be sufficient to control the disease during study participation.
- •If applicable, maintained stable dose of neuropsychiatric medication (ie, for ADHD, depression, anxiety, or other psychiatric disorders) prior to enrollment (as described in Section 6.6.1 of the protocol) and willing to maintain stable dose throughout study participation unless, per Investigator assessment, a change is clinically indicated.
- •Sexually active females of childbearing potential and sexually active males of reproductive potential must agree to use a highly effective method of contraception during the study, and for 3 months following the last administration of the study intervention (Section 10.4.2 of the protocol).
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Receipt of sapropterin or large-neutral amino acids within 14 days or 5 half-lives (whichever is longer) of the start of Screening.
- •Positive HBsAg, positive PCR for HCV RNA, or HIV (positive HIV1/HIV-2 antibodies). Note: Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible for study participation. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA (Section 8.2.3.3).
- •History of hypersensitivity to any component/excipient used in this study.
- •History of hypersensitivity or contraindication to acetaminophen/paracetamol and/or ibuprofen or H1/H2 receptor blockers.
- •Participant has a history of anaphylaxis or severe hypersensitivity reactions to PEG (including, but not limited to, PEGylated LNP COVID-19 vaccines and other PEG-containing medications or products) or polysorbates.
- •Laboratory abnormality within an exclusionary threshold at Screening (Table 10) and/or any clinically relevant abnormal laboratory values at Screening per Investigator criteria.
- •Glomerular filtration rate <30 mL/min/1.73 m2 as estimated by the 2021 CKD-EPI creatinine equation.
- •Participants who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.
- •Participants who, in the Investigator’s opinion, are cognitively impaired and unable to complete study procedures such as the PRO assessments or providing consent.
- •Any other clinically significant medical condition (including but not limited to unstable cardiovascular disease, acute kidney, or liver failure) that, in the Investigator’s opinion, could interfere with the interpretation of study results or limit the participant’s participation in the study, or could potentiate the risk while participating in the study.
- •Participant plans to receive a COVID vaccine any time after 28 days before the first dose of study intervention and before 7 days after the third dose of study intervention.
- •Participants with BH4 deficiency or DNAJC12 deficiency confirmed by genetic testing from a central lab. Note: Genetic testing for BH4 and DNAJC12 deficiency can be obtained during the Limited Screening Period as described in Section 4.1.
- •History of substance or alcohol abuse that in the Investigator’s assessment would impair the participant’s ability to comply with the protocol.
- •Receipt of pegvaliase within 2 months of start of Screening (see Section 6.6 of the protocol).
- •For patients previously on pegvaliase: use or planned use of any injectable drugs containing PEG, including medroxyprogesterone injection, within 3 months prior to the start of Screening and during study participation with the exception of COVID-19 vaccinations (as described in Section 5.2 and Section 6.6.2 of the protocol).
- •Receipt of any investigational drug within 30 days or 5-half-lives (whichever is longer) of Screening.
- •Intake of medications known to interfere with folate metabolism (eg, aminopterin, methotrexate (amethopterin), pyrimethamine, trimethoprim, triamterene, etc.) within 14 days or 5 half-lives (whichever is longer) of start of Screening.
- •Having received gene therapy with PAH at any time previously.
- •Median QTcF of triplicate standard 12-lead ECGs >450 msec at Screening.
- •For female participants of reproductive potential, positive pregnancy test at Screening or Day 1 or currently breastfeeding.
结局指标
主要结局
Number of participants with TEAEs.
Number of participants with TEAEs.
次要结局
- • Changes from baseline in blood Phe levels. • Characterization of PD parameters, including Emax, AUEC, and duration of response.
- • Characterization of blood PK parameters of mRNA and SM 86, including, but not limited to, Cmax, Tmax, AUC, t½, CL, and Vz.
- • Presence and titers of anti-PEG antibodies.
研究者
Moderna Clinical Trials
Scientific
Moderna Therapeutics Inc.
研究点 (7)
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