A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain

Phase 1

Completed

Conditions: Radiculopathy Lumbar

Interventions: Drug: Placebo
Drug: LAT8881

Registration Number: NCT05298306

Lead Sponsor: Lateral Pharma Pty Ltd

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. 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. Subjects in Part A are randomized to receive placebo and LAT8881 according to the following treatment sequences. Two subjects are allocated to each treatment sequence, a total of eight subjects overall.

0.8 mg/kg/1.2 mg/kg/1.8 mg/kg;

0.8 mg/kg/1.2 mg/kg/Placebo;

0.8 mg/kg/Placebo/1.8 mg/kg;

Placebo/1.2 mg/kg/1.8 mg/kg.

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 either a 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

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 (NRS) 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo will be given as a single intravenous infusion in Part A and Part B
LAT8881	LAT8881	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.

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Adverse Events by Dose (Part A)	From first dose of LAT8881 to end of study visit (Day 14)	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)	From start of infusion to 6 hours after start of infusion	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

Name	Time	Method
Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A)	Up to 6 hours after the start of each infusion	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)	Up to 6 hours after the start of each infusion	LAT8881 was 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)	Up to 6 hours after the start of each infusion	LAT8881 was 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) was calculated only if there were at least three quantifiable data points.
Terminal Elimination Half Life (T1/2), (Part A)	Up to 6 hours after the start of each infusion	LAT8881 was 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 was only determined if there were at least three quantifiable elimination phase data points.
Patient General Impression of Change (Part B)	6 hours after the start of each infusion	The Patient General Impression of Change (PGIC) is a single-item rating by subjects of their improvement with treatment during a clinical trial. Participants were asked to select one of the following options after each treatment: very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse.
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B)	From start of infusion to end of study visit (Day 9)	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