Back to resultsA Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain
Primary Purpose
Radiculopathy Lumbar
Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
LAT8881
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Radiculopathy Lumbar
Eligibility Criteria
Key Inclusion Criteria:
For PART A, the following inclusion criteria apply:
- Male or female healthy participants, aged 18-49 years inclusive at screening;
- Body mass index of ≥ 19.0 kg/m2 to ≤ 32.0 kg/m2 at screening;
- Female participants must not be pregnant or breastfeeding
- Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment
For PART B, the following key inclusion criteria apply:
- Male or female participants with unilateral pain, aged 18-65 years inclusive at screening;
- Body mass index of ≥ 19.0 kg/m2 to ≤ 35.0 kg/m2 at screening.
- Female participants must not be pregnant or breastfeeding
- Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment
- Presenting with a history of unilateral pain, radiating into a lower limb, of lancinating, burning, stabbing or electric quality, of duration of 3 months to 12 months.
- Pain scores (VAS) for average daily leg pain at rest at the relevant nerve root of a mean of ≥4/10 and ≤9/10 for 3 days prior to treatment, with a minimum of >3/10 on any day.
- Demonstration of a disc herniation within 6 months by CT or MRI at a segmental level consistent with the clinical features.
- The site of the disc herniation must affect L1-2, L2-3, L3-4, L4-5 or L5-S1.
- The patient is willing to keep all analgesic medication and other therapy usage stable or decreased in the week prior to, and a week after, IP administration.
- The patient is in good general health, with the exception of the presenting condition under study
Key Exclusion Criteria:
The following key exclusion criteria apply for both PART A and PART B:
- Any condition which might be a risk to participant safety or interfere with study evaluation
- Unwillingness to abstain from alcohol or nicotine products as required
The following additional key exclusion criteria apply to PART B:
- A history of significant pain unrelated to disc herniation that would significantly compromise assessment of leg radicular pain.
- Clinical evidence of radicular pain at more than one spinal nerve.
- Radiological evidence of foraminal stenosis or of clinically significant spinal stenosis .
- Lumbar back surgery related to the specific disc.
- Injection of an epidural corticosteroid injection within 3 months of screening.
Sites / Locations
- PARC Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LAT8881
Placebo
Arm Description
In Part A, LAT8881 will be given as a single intravenous infusion on separate days at doses of 0.8, 1.2 and 1.8 mg/kg. In Part B, LAT8881 will be given as a single intravenous infusion. The dose will be determined from the results of Part A.
Matching placebo will be given as a single intravenous infusion in Part A and Part B
Outcomes
Primary Outcome Measures
The number of participants with adverse events by dose (Part A)
The number of participants in Part A with the following adverse events will be reported by dose (with all placebo subjects combined)
All adverse events
Serious adverse events
Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP)
Adverse events by intensity
Adverse events by relationship to IMP
Change in baseline pain with intravenous LAT8881 in patients with lumbar radicular pain (Part B)
Change in pain from baseline is measured on on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10.
VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement
Secondary Outcome Measures
Maximum plasma LAT8881 concentration (Cmax) after intravenous LAT8881 (Part A)
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Time to maximum plasma LAT8881 concentration (Tmax) after intravenous LAT8881 (Part A)
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) after intravenous LAT8881 (Part A)
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. (AUC0-inf) will only be calculated if there are at least three quantifiable data points
Terminal elimination half life (T1/2), (Part A)
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. The terminal elimination half life will only be determined if there are at least three quantifiable elimination phase data points.
Patient general impression of change (Part B)
The Patient General Impression of Change (PGIC) is a a single-item rating by subjects of their improvement with treatment during a clinical trial. It asks the subject to rate their improvement with therapy on a 7-point scale, ranging from substantially worse ("0") to substantially improved ("7"), with no change ("4") as the mid-point. A score above 4 indicates an improvement.
The number of participants with adverse events after intravenous LAT8881 in patients with lumbar radicular pain (Part B)
The number of participants in Part B with the following adverse events will be reported after placebo and after intravenous LAT8881
All adverse events
Serious adverse events
Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP)
Adverse events by intensity
Adverse events by relationship to IMP
Full Information
NCT ID
NCT05298306
First Posted
March 3, 2022
Last Updated
July 27, 2023
Sponsor
Lateral Pharma Pty Ltd
Collaborators
Southern Star Research Pty Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05298306
Brief Title
A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain
Official Title
A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
May 17, 2022 (Actual)
Primary Completion Date
May 12, 2023 (Actual)
Study Completion Date
June 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lateral Pharma Pty Ltd
Collaborators
Southern Star Research Pty Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study consists of two parts. Part A will evaluate the safety and tolerability of intravenous LAT8881 in healthy volunteers using an ascending dose schedule. Part B will evaluate the analgesic efficacy of a single intravenous dose of LAT8881, compared with placebo, in patients with lumbar radicular pain.
Healthy volunteers are not accepted for Part B.
Detailed Description
Part A of this study is a double-blind, randomized, placebo-controlled, single ascending dose study of intravenous administration of LAT8881 over 5 minutes in healthy volunteers. Eight participants will be enrolled. Each participant has three treatment days, 1 infusion per dosing day, on Days 1, 4 and 7 as well as two short visits for safety blood sampling on Days 3 and 6. Participants are randomised, so on each treatment day, 6 participants receive LAT8881 and 2 receive placebo (different participants to receive placebo each treatment day). LAT8881 doses administered are 0.8 mg/kg on Day 1, 1.2 mg/kg on Day 4 and 1.8 mg/kg on Day 7.
Part B of this study is is a placebo-controlled randomized double blind cross-over safety and efficacy study of LAT8881 in up to 20 patients with lumbar radicular pain. Participants will be randomly assigned to one of two groups, to receive either LAT8881 then placebo or placebo then LAT8881. Participants will receive a either single dose of LAT8881 [the Maximum Tolerated Dose from Part A of the study] or placebo via intravenous administration over 5 minutes on two consecutive days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radiculopathy Lumbar
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LAT8881
Arm Type
Experimental
Arm Description
In Part A, LAT8881 will be given as a single intravenous infusion on separate days at doses of 0.8, 1.2 and 1.8 mg/kg.
In Part B, LAT8881 will be given as a single intravenous infusion. The dose will be determined from the results of Part A.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo will be given as a single intravenous infusion in Part A and Part B
Intervention Type
Drug
Intervention Name(s)
LAT8881
Intervention Description
In Part A, LAT8881 will be given as a single intravenous infusion at doses of 0.8, 1.2 and 1.8 mg/kg.
In Part B, a single intravenous infusion of LAT8881 will be given, the dose to be determined by the results in Part A
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo'given as a single intravenous infusion at all dose levels
Primary Outcome Measure Information:
Title
The number of participants with adverse events by dose (Part A)
Description
The number of participants in Part A with the following adverse events will be reported by dose (with all placebo subjects combined)
All adverse events
Serious adverse events
Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP)
Adverse events by intensity
Adverse events by relationship to IMP
Time Frame
From first dose of LAT8881 to end of study visit (Day 14)
Title
Change in baseline pain with intravenous LAT8881 in patients with lumbar radicular pain (Part B)
Description
Change in pain from baseline is measured on on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10.
VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement
Time Frame
From start of infusion to 6 hours after start of infusion
Secondary Outcome Measure Information:
Title
Maximum plasma LAT8881 concentration (Cmax) after intravenous LAT8881 (Part A)
Description
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Time Frame
Up to 6 hours after the start of each infusion
Title
Time to maximum plasma LAT8881 concentration (Tmax) after intravenous LAT8881 (Part A)
Description
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Time Frame
Up to 6 hours after the start of each infusion
Title
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) after intravenous LAT8881 (Part A)
Description
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. (AUC0-inf) will only be calculated if there are at least three quantifiable data points
Time Frame
Up to 6 hours after the start of each infusion
Title
Terminal elimination half life (T1/2), (Part A)
Description
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. The terminal elimination half life will only be determined if there are at least three quantifiable elimination phase data points.
Time Frame
Up to 6 hours after the start of each infusion
Title
Patient general impression of change (Part B)
Description
The Patient General Impression of Change (PGIC) is a a single-item rating by subjects of their improvement with treatment during a clinical trial. It asks the subject to rate their improvement with therapy on a 7-point scale, ranging from substantially worse ("0") to substantially improved ("7"), with no change ("4") as the mid-point. A score above 4 indicates an improvement.
Time Frame
6 hours after the start of the second infusion
Title
The number of participants with adverse events after intravenous LAT8881 in patients with lumbar radicular pain (Part B)
Description
The number of participants in Part B with the following adverse events will be reported after placebo and after intravenous LAT8881
All adverse events
Serious adverse events
Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP)
Adverse events by intensity
Adverse events by relationship to IMP
Time Frame
From start of infusion to end of study visit (Day 9)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria:
For PART A, the following inclusion criteria apply:
Male or female healthy participants, aged 18-49 years inclusive at screening;
Body mass index of ≥ 19.0 kg/m2 to ≤ 32.0 kg/m2 at screening;
Female participants must not be pregnant or breastfeeding
Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment
For PART B, the following key inclusion criteria apply:
Male or female participants with unilateral pain, aged 18 years and above at screening;
Body mass index of ≥ 19.0 kg/m2 at screening.
Female participants must not be pregnant or breastfeeding
Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment
Presenting with a history of unilateral pain, radiating into a lower limb, of lancinating, burning, stabbing or electric quality, of duration of >3 months.
Pain scores (VAS) for average daily leg pain at rest at the relevant nerve root of a mean of ≥4/10 and ≤9/10 for 3 days prior to treatment, with a minimum of >3/10 on any day.
Demonstration of disc herniation within 6 months by CT or MRI at a segmental level consistent with the clinical features.
The site of disc herniation must affect L1-2, L2-3, L3-4, L4-5 or L5-S1.
The patient is willing to keep all analgesic medication and other therapy usage stable or decreased in the week prior to, and a week after, IP administration.
The patient is in good general health, with the exception of the presenting condition under study
Key Exclusion Criteria:
The following key exclusion criteria apply for both PART A and PART B:
Any condition which might be a risk to participant safety or interfere with study evaluation
Unwillingness to abstain from alcohol or nicotine products as required
The following additional key exclusion criteria apply to PART B:
A history of significant pain unrelated to disc herniation that would significantly compromise assessment of leg radicular pain.
Radiological evidence of foraminal stenosis or of clinically significant spinal stenosis .
Lumbar back surgery related to the specific disc.
Injection of an epidural corticosteroid injection within 3 months of screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guy Ludbrook, MBBS
Organizational Affiliation
Royal Adelaide Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
PARC Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
12. IPD Sharing Statement
Learn more about this trial
A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain
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