Persica 002 Phase 1b PP353 vs Placebo in the Treatment of Low Back Pain

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Chronic Low-back Pain

Intervention / Treatment
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* Drug: PP353
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PP353<br> | Drug: PP353<br>* active administered by intradiscal injection<br>|
| Placebo Comparator: Sham injection<br> | Other: Placebo<br>* Sham injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | 12 months | 
| Change from baseline in Low Back Pain Numerical Rating Scale (LBP NRS) score | 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: Low back pain intensity now Worst low back pain intensity in the last 14 days Average low back pain intensity over the last 14 days | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Low Back Pain Numerical Rating Scale (LBP NRS) score | 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: Low back pain intensity now Worst low back pain intensity in the last 14 days Average low back pain intensity over the last 14 days | 3, 6 & 9 months | 
| Change from baseline in Roland Morris Disability Questionnaire-23 score |  | 3, 6, 9 & 12 months | 
| Clinically relevant improvement | 30 percent reduction from baseline in Roland Morris Disability Questionnaire-23 score | 3, 6, 9 &12 months | 
| Change from baseline in Oswestry Disability Index |  | 3, 6 & 12 months | 
| Plasma pharmacokinetics - Tdur (duration above a prescribed threshold) |  | 11 days | 
| Plasma pharmacokinetics - tmax (the time at which Cmax was apparent) |  | 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 - CL/F (the systemic clearance calculated from plasma) |  | 11 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Back pain, Low back pain, Lower back pain, Modic