Chronic Low-back Pain
Conditions
Keywords
Back pain, Low back pain, Lower back pain, Modic
Brief summary
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
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.
Interventions
DRUGPP353
active administered by intradiscal injection
OTHERPlacebo
Sham injection
Sponsors
Persica Pharmaceuticals Ltd
Micron Research Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part A is open label In Part B the pharmacist and injector will not be blinded to treatment allocation
Intervention model description
Part A is open label Part B is parallel placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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: 1. in the opinion of the investigator, after deep palpation of the vertebral spine, is contributing to the low back pain and/or 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | 0 to 12 months | All causality Treatment Emergent Adverse Events. Any event that was not present prior to the initiation of the treatment, or any event that was already present but increased in intensity or frequency following treatment, was recorded as a treatment-emergent adverse event |
| Change From Baseline in Low Back Pain Numerical Rating Scale (LBP NRS) Score | 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." A lower score indicates less pain. The Low Back Pain Numerical Rating 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 Part A PP353 was an open label arm (3 participants): this outcome measure was not determined. No summary analyses were conducted for efficacy in Part A. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Roland Morris Disability Questionnaire-23 Score | 12 months | The Roland Morris Disability Questionnaire (RMDQ)-23 is a self-administered disability measure consisting of 23 questions. Participants are asked to read a list of 23 sentences and answer "yes" or "no" to each question depending on how the participant feels each sentence describes them today. . The total number of "yes" responses gives a score from 0 to 23. A lower score indicates less disability. Participants required a score of at least 9 to enter the study Part A PP353 was an open label arm (3 participants): this outcome measure was not determined. No summary analyses were conducted for efficacy in Part A. |
| Clinically Relevant Improvement (≥30%) in RMDQ-23 | 12 months | The Roland Morris Disability Questionnaire (RMDQ)-23 is a self-administered disability measure consisting of 23 questions. Participants are asked to read a list of 23 sentences and answer "yes" or "no" to each question depending on how the participant feels each sentence describes them today. . The total number of "yes" responses gives a score from 0 to 23. A lower score indicates less disability. Participants required a score of at least 9 to enter the study Part A PP353 was an open label arm (3 participants): this outcome measure was not determined. No summary analyses were conducted for efficacy in Part A. |
| Change From Baseline in Oswestry Disability Index | 12 months | The ODI is a subject-completed questionnaire which gives a subjective percentage score of level of function (disability) in activities of daily living. A lower score indicates less disability. Scores are interpreted as follows: 0-20%: minimal disability 21-40%: moderate disability 41-60%: severe disability 61-80% crippled 81-100%: bed-bound Part A PP353 was an open label arm (3 participants): this outcome measure was not determined. No summary analyses were conducted for efficacy in Part A. |
Countries
Denmark, New Zealand, Spain, United Kingdom
Contacts
STUDY_CHAIRDuncan McHale, MBBS MRCP
Weatherden Ltd
Participant flow
Recruitment details
3 participants were recruited into Part A and 40 in Part B. Participants were recruited through community and hospital pain clinics, referrals from other centres and social media campaigns, between Jan 2020 to Dec 2023, at 10 trial sites: 6 in the UK, 2 in Spain, 1 in New Zealand and 1 in Denmark For Part B, the Full Analysis Set consisted of all enrolled subjects who received at least one dose of PP353 or placebo and had a valid post-baseline measurement for at least one efficacy variable.
Pre-assignment details
In Part A, 9 participants were screened, 3 of whom were included in the study. No summary analyses were conducted for efficacy in Part A. In Part B, 136 participants were screened, 40 of whom were randomised and met the criteria to be included in the Full Analysis Set (FAS).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants |
| Age, Continuous | 44 Years STANDARD_DEVIATION 6.82 |
| Low Back Pain Numerical Rating Scale (LBP NRS) Score | 6.9 Score (0-10) STANDARD_DEVIATION 1.52 |
| Race and Ethnicity Not Collected | 0 Participants |
| Roland Morris Disability Questionnaire-23 Score (RMDQ-23) | 14.9 Score (0-23) STANDARD_DEVIATION 3.83 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 3 / 3 | 15 / 20 | 18 / 20 |
| serious Total, serious adverse events | 0 / 3 | 0 / 20 | 1 / 20 |
Outcome results
None listed