Clinical trial NCT05298306: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Radiculopathy Lumbar
Lead sponsor: Lateral Pharma Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Southern Star Research
First posted: 2022-03-28
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The crossover study (Part B) is preceded by a single ascending dose study (Part A)
Primary purpose: TREATMENT

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.

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 (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.

Primary outcomes:
measure: The Number of Participants With Adverse Events by Dose (Part A)
timeFrame: From first dose of LAT8881 to end of study visit (Day 14)
measure: Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B)
timeFrame: From start of infusion to 6 hours after start of infusion
Secondary outcomes:
measure: Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A)
timeFrame: Up to 6 hours after the start of each infusion
measure: Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A)
timeFrame: Up to 6 hours after the start of each infusion
measure: Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A)
timeFrame: Up to 6 hours after the start of each infusion
measure: Terminal Elimination Half Life (T1/2), (Part A)
timeFrame: Up to 6 hours after the start of each infusion
measure: Patient General Impression of Change (Part B)
timeFrame: 6 hours after the start of each infusion
measure: The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B)
timeFrame: From start of infusion to end of study visit (Day 9)
Other outcomes:
measure: The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch.
timeFrame: From start of infusion to 6 hours after start of infusion
Locations:
city: Adelaide
country: Australia
facility: PARC Clinical Research
state: South Australia
Study officials:
affiliation: Royal Adelaide Hospital
name: Guy Ludbrook, MBBS
role: PRINCIPAL_INVESTIGATOR
References: