A Phase 1b Study Investigating the Safety, Tolerability and Efficacy of PP353 in the Treatment of Patients With Chronic Low Back Pain Associated With Vertebral Body Endplate Bone Oedema (Modic 1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 10
- 主要终点
- Change from baseline in Low Back Pain Numerical Rating Scale (LBP NRS) score
研究概览
简要总结
A Phase 1b study to investigate the efficacy of PP353 compared to placebo in the treatment of chronic low back pain associated with bone oedema.
详细描述
A 2-part study. In the first part the safety, tolerability and pharmacokinetics will be assessed in up to 6 participants. In the second part, the safety, tolerability and efficacy of PP353 will be assessed in up to 40 participants.
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
The pharmacist and injector will not be blinded to treatment allocation
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and 70 years, inclusive.
- •Chronic low back pain in the area associated with vertebral body endplate bone oedema (Modic 1) or vertebral body endplate bone oedema and fat (Modic 1 and 2) at a single lumbar level.
- •Average LBP NRS score at screening and at Day 1 pre-randomisation ≥ 4 on chronic pain medication and ≥ 6 if not on chronic pain medication; it should be higher than the leg pain NRS score
- •RMDQ-23 score ≥ 9 at screening and at Day 1 pre-randomisation.
- •Current episode of chronic low back pain has lasted for ≥ 6 months at the time of randomisation.
- •Bodyweight of ≥ 50 kg and ≤ 120 kg.
- •Failure of standard of care therapies used by their treating physician
排除标准
- •Any vertebra with Modic 2 only lesions which:
- •in the opinion of the investigator, after deep palpation of the vertebral spine, is contributing to the low back pain and/or
- •are present within 2 vertebrae from the target lumbar disc.
- •The target lumbar disc has lost more than half its original anticipated height at the centre or it is < 5mm in height over the central 15 mm portion
- •A clear alternative cause for back pain
- •Gross facet joint degeneration or cases where the investigator believes the primary pain generator to be the facet joints
- •Interventional back procedure in the 6 months prior to screening or major surgery in the 12 weeks prior to screening
- •History of alcohol abuse or drugs of abuse in the past 2 years
- •Any other significant illness
- •Previously been treated with antimicrobial agents for their low back pain or previously received any antimicrobial intradiscal injection.
研究组 & 干预措施
PP353
干预措施: PP353 (Drug)
Sham injection
干预措施: Placebo (Other)
结局指标
主要结局
Change from baseline in Low Back Pain Numerical Rating Scale (LBP NRS) score
时间窗: 12 months
Each question will be assessed by the subject on an 11-point scale with 0 = "no pain" and 10 = "the worst possible pain you can imagine." The LBP NRS score throughout this protocol is defined as the average of the score of the three questions: 1. Low back pain intensity now 2. Worst low back pain intensity in the last 14 days 3. Average low back pain intensity over the last 14 days
Incidence of adverse events
时间窗: 12 months
次要结局
- Change from baseline in Roland Morris Disability Questionnaire-23 score(3, 6, 9 & 12 months)
- Change from baseline in Low Back Pain Numerical Rating Scale (LBP NRS) score(3, 6 & 9 months)
- Clinically relevant improvement(3, 6, 9 &12 months)
- Plasma pharmacokinetics - Tdur (duration above a prescribed threshold)(11 days)
- Plasma pharmacokinetics - the area under the concentration versus time curve within a dosing interval(11 days)
- Plasma pharmacokinetics - Cmax (the maximum observed concentration)(11 days)
- Plasma pharmacokinetics - t½ (the apparent terminal half-life)(11 days)
- Plasma pharmacokinetics - tmax (the time at which Cmax was apparent)(11 days)
- Plasma pharmacokinetics - CL/F (the systemic clearance calculated from plasma)(11 days)
- Change from baseline in Oswestry Disability Index(3, 6 & 12 months)