A Randomized, Double-Blind, Placebo-Controlled Phase 1/2a Trial of PRO-1562 in Healthy Adults and Adults With Multiple Sclerosis and Chronic Optic Neuropathy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Phase 1 Incidence of ≥Grade 2 treatment-emergent adverse events
研究概览
简要总结
Phase 1 will test single oral doses of PRO-1562 in healthy adult subjects to characterize the safety and the amount of drug that is absorbed into the body. Some subjects will have lumbar punctures performed to measure the amount of drug that crosses the blood-brain barrier since that is the site of drug activity.
Phase 2a will be a 6-month trial to test the ability of once monthly dosing of PRO-1562 to promote remyelination of the CNS and provide clinical benefit to adult patients with relapsing multiple sclerosis (RMS) who also have long-term vision problems diagnosed as chronic optic neuropathy. The benefits of remyelination will be measured using tests of visual acuity, speed of optic nerve conduction signals, and clinical assessments of cognitive and motor function. PRO-1562 will be added on to a stable regimen of MS disease modifying therapy.
详细描述
Phase 1 is a randomized, double-blind, placebo-controlled, single-ascending dose (SAD) trial of PRO-1562 in healthy adult participants at a single clinical research unit to characterize the safety and pharmacokinetics of a range of oral doses of PRO-1562. Phase 2a is a randomized, double-blind, placebo-controlled, multi-center, 6-month trial of PRO-1562 in adult patients with relapsing multiple sclerosis who also have chronic optic neuropathy. Patients will remain on their stable regimen of an approved MS disease modifying therapy during the trial. Oral PRO-1562 or placebo will be dosed once a month at scheduled clinic visits. Participants will be given the option to continue on their assigned study treatment after completing the 6-month treatment period until the last patient completes the 6-month treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Phase 1 Inclusion Criteria:
- •Able and willing to provide written informed consent
- •Body weight ≥ 48 kg (105.6 lbs) and body mass index (BMI) ≥ 18.5 and ≤ 30 kg/m2
- •Must be in good health and without clinically significant abnormalities by review of medical and surgical history, physical examination, vital signs measurement, and 12-lead ECG
- •No clinically-significant laboratory abnormalities
- •Willing and able to use highly-effective forms of contraception for at least 30 days after the end of study visit.
排除标准
- •Ongoing medical condition requiring systemic therapy.
- •Ongoing infection
- •mRNA or live vaccine during the past 60 days
- •History of significant hypersensitivity, intolerance, or allergy to any drug/medication
- •Participation in another clinical trial with an investigational agent within 30 days prior to Check-in or 5 half-lives (if known) of the investigational drug's PK, PD, or biological activity (if known), whichever is longer
- •Positive alcohol breath test or urine screen for drugs of abuse.
- •Use or intent to use natural products or nutritional/dietary supplements (including St. John's wort), vitamins, minerals, and phytotherapeutic /herbal/plant-derived preparations within or received within 14 days or 5 half-lives prior to Check-in, whichever is longer.
- •Poor peripheral venous access.
- •Receipt of blood products within 2 months prior to Check-in.
- •Donation of blood or blood products during the 4 weeks prior to Check-in.
- •Participants who in the opinion of the Principal Investigator (or designee), should not participate in this study
研究组 & 干预措施
Phase 1, PRO-1562 Dose level 1
PRO-1562 oral capsule
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, PRO-1562 Dose level 2
PRO-1562 oral capsule
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, PRO-1562 Dose level 3
PRO-1562 oral capsule
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, PRO-1562 Dose level 4
PRO-1562 oral capsules
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, PRO-1562 Dose level 5
PRO-1562 oral capsule
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, PRO-1562 Dose level 6
PRO-1562 oral capsule
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 1, Placebo
Placebo oral capsule
干预措施: Placebo Oral Capsule (Drug)
Phase 2, PRO-1562 Oral Capsules Dose level 1
PRO-1562 low dose level selected from Phase 1 (oral capsule)
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 2, PRO-1562 Oral Capsules Dose level 2
PRO-1562 high dose level selected from Phase 1 (oral capsule)
干预措施: PRO-1562 Oral Capsules (Drug)
Phase 2, Placebo
Placebo oral capsule
干预措施: Placebo Oral Capsule (Drug)
结局指标
主要结局
Phase 1 Incidence of ≥Grade 2 treatment-emergent adverse events
时间窗: From enrollment until 7 days post dose
Incidence of treatment-emergent adverse events including clinically significant laboratory abnormalities of ≥Grade 2 in healthy participants
Phase 2 Change from baseline P100 VEP latency
时间窗: From enrollment until the end of 6 months of treatment
The change from baseline on visual evoked potential (VEP) in affected eye of RMS patients after 6 months of study treatment
次要结局
- Area under the concentration-time curve of PRO-1562 (Phase 1)(From enrollment until 7 days post dose.)
- Brain myelin content, change from baseline(From enrollment to the end of 6 months of treatment)
- Safety Phase 2 Incidence of ≥Grade 2 treatment-emergent adverse events(From enrollment until the end of 6-months of treatment)