A Phase 1/2 Randomized, Blinded, Dose-escalation Study to Evaluate the Safety and Efficacy of Intrathecal Administration of AAV9-ABCD1 Gene Therapy (SBT101) in Adult Patients With Adrenomyeloneuropathy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Adverse Events to SBT101
研究概览
简要总结
This is a Phase 1/2 randomized, blinded, dose-escalation study to evaluate the safety and efficacy of intrathecal (IT) administration of SBT101, a recombinant adeno-associated virus serotype 9 (AAV9) containing a functional copy of the human adenosine triphosphate (ATP)-binding cassette transporter subfamily D member 1 (ABCD1; hABCD1) gene, in adult patients with adrenomyeloneuropathy (AMN) aged 18-65 years.
Patients will receive a single dose of SBT101 via IT route (or an imitation procedure) and will be followed for safety and efficacy for 2 years. Patients receiving SBT101 will be followed for an additional 3 years (5 total) for Safety. Patients receiving an imitation procedure will be offered the opportunity to receive SBT101 after 2 years, as data indicate.
详细描述
The study consists of two parts after infusion of SBT101:
Part 1: A blinded 24-month core study period to evaluate the safety and potential impact of SBT101 on disease progression. Part 1 will consist of 2 phases:
Phase 1: Dose-Escalation Phase: Two (2) doses of SBT101 (Dose level 1 cohort and Dose Level 2 cohort) will be evaluated to establish the maximum tolerated dose (MTD).
Phase 2: Dose-Expansion Phase: Additional patients will be enrolled to receive SBT101 at the MTD
Part 2: An unblinded 3-year long-term safety follow-up period with annual follow-up visits to evaluate the safety of SBT101 and disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Maintain masking to all but those are perform the actual procedure
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with X-linked adrenoleukodystrophy (ALD), including proven mutation in the ABCD1 gene through confirmatory genetic testing, and supported by elevated circulating VLCFA levels.
- •Clinical evidence of spinal cord involvement but still able to ambulate independently
排除标准
- •Evidence of or past diagnosis of inflammatory cerebral disease.
- •15 years or more have elapsed since the initial onset of myeloneuropathy manifestations such as walking or running difficulties, bladder dysfunction, increased muscular tone, spasticity, weakness, balance problems, etc.
- •Contraindications for MRI procedure and/or contrast materials.
- •Contraindication to steroids, sirolimus, tacrolimus, and/or anesthetic medications.
- •Unstable adrenal function (e.g., untreated or inappropriately treated adrenal insufficiency).
- •History of diabetes or abnormal fasting plasma glucose (≥126 mg/dL) or hemoglobin A1C ≥6.5%.
- •Patients who have received a gene therapy.
结局指标
主要结局
Adverse Events to SBT101
时间窗: 2 years
Safety and tolerability of SBT101 administration
Adverse Events to SBT101. Any Serious TEAE. Any Serious TEAE Related to the Study Procedure or Study Drug.
时间窗: 2 years
Any Treatment Emergent Adverse Event (TEAE). TEAE was defined as any adverse event which started during or after the administration of IMP or the immunosuppressant pre-medication.
次要结局
- Disease progression(2 years)