NCT04984278: RELEASE MSS5

Evaluation of the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Participants With Multiple Sclerosis

Terminated Phase 3 Results posted Last updated 11 December 2024

What this trial tests

Phase 3 trial testing Nabiximols in Spasticity With Multiple Sclerosis in 56 participants. Terminated before completion.

Timeline

16 August 2021

Primary endpoint
11 November 2022

11 November 2022

Quick facts

Lead sponsor	Jazz Pharmaceuticals
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	56
Start date	16 August 2021
Primary completion	11 November 2022
Estimated completion	11 November 2022
Sites	30 locations across United Kingdom, Poland, United States, Spain, Czechia

Drugs / interventions tested

• Nabiximols — full drug profile →
• Placebo

Conditions studied

• Spasticity With Multiple Sclerosis — all drugs for Spasticity With Multiple Sclerosis →

Sponsor

Jazz Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Spasticity With Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Lower Limb Muscle Tone-6 (LLMT-6) Primary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-6 score is being reported. Negative values indicate an improvement in muscle tone.

Group	Value	95% CI
Nabiximols	-0.32	± 0.072
Placebo	-0.04	± 0.075

Change From Baseline in Lower Limb Muscle Tone-4 (LLMT-4) Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

LLMT-4 is defined as the average of the 4 individual MAS transformed scores of knee flexors and knee extensors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-4 score is being reported. Negative values indicate an improvement in muscle tone.

Group	Value	95% CI
Nabiximols	-0.34	± 0.079
Placebo	-0.09	± 0.082

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product.

Group	Value	95% CI
Nabiximols	19
Placebo	6

Change From Baseline in Blood Pressure Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Systolic blood pressure

Group	Value	95% CI
Nabiximols	-2.5	± 11.27
Placebo	-4.4	± 8.26

Diastolic blood pressure

Group	Value	95% CI
Nabiximols	-1.9	± 7.74
Placebo	-2.8	± 7.66

Change From Baseline in Heart Rate Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Group	Value	95% CI
Nabiximols	0.9	± 8.97
Placebo	-0.1	± 9.13

Change From Baseline in Clinical Laboratory Test Values Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Leukocytes

Group	Value	95% CI
Nabiximols	0	± 1.68
Placebo	-0.07	± 1.94

Neutrophils

Group	Value	95% CI
Nabiximols	0.071	± 0.94
Placebo	-0.399	± 0.53

Basophils

Group	Value	95% CI
Nabiximols	-0.01	± 0.07
Placebo	0	± 0.07

Eosinophils

Group	Value	95% CI
Nabiximols	0.04	± 0.22
Placebo	0.04	± 0.19

Lymphocytes

Group	Value	95% CI
Nabiximols	-0.041	± 0.48
Placebo	0.033	± 0.48

Monocytes

Group	Value	95% CI
Nabiximols	0.01	± 0.22
Placebo	0.03	± 0.20

Platelets

Group	Value	95% CI
Nabiximols	2.4	± 23.20
Placebo	4.6	± 25.91

Change From Baseline in Erythrocytes Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Group	Value	95% CI
Nabiximols	-0.138	± 0.20
Placebo	-0.090	± 0.19

Change From Baseline in Hemoglobin Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Group	Value	95% CI
Nabiximols	-0.34	± 0.62
Placebo	-0.21	± 0.53

Change From Baseline in Hematocrit Ratio Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Hematocrit was measured in whole blood samples. The ratio of packed cells to total volume was assessed. Normal ratio ranges from 0.350-0.470 female and 0.400-0.540 male (normal ranges per our central lab), 0.37 (or 37%) to 0.52 (or 52%) in adults. Lower hematocrit ratios indicate worse clinical outcome.

Group	Value	95% CI
Nabiximols	-0.012	± 0.0191
Placebo	-0.009	± 0.0191

Change From Baseline in Erythrocyte Mean Corpuscular Volume Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Group	Value	95% CI
Nabiximols	-0.12	± 2.08
Placebo	-0.38	± 1.89

Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Group	Value	95% CI
Nabiximols	0.1	± 0.64
Placebo	0.1	± 0.57

Change From Baseline in Electrocardiogram Parameters Secondary · Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

PR duration

Group	Value	95% CI
Nabiximols	-3.1	± 27.35
Placebo	0.5	± 26.78

QRS duration

Group	Value	95% CI
Nabiximols	2.0	± 6.10
Placebo	1.7	± 5.54

QT interval

Group	Value	95% CI
Nabiximols	5.4	± 15.35
Placebo	4.0	± 17.79

QTcB interval

Group	Value	95% CI
Nabiximols	-0.8	± 16.04
Placebo	4.9	± 15.20

QTcF interval

Group	Value	95% CI
Nabiximols	2.5	± 12.60
Placebo	5.2	± 13.84

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse event (TEAE) data were collected from baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nabiximols

Serious: 0/30 (0%)

Deaths: 0/30

Placebo

Serious: 0/30 (0%)

Deaths: 0/30

Other adverse events (2 terms — click to expand)

Reaction	System	Nabiximols	Placebo
Fatigue	General disorders	—	—
Vertigo	Ear and labyrinth disorders	—	—

Data from ClinicalTrials.gov NCT04984278 adverse events section.

Sponsor's own description

This study will be conducted to evaluate the effect of multiple doses of nabiximols compared with placebo on a clinical measure of velocity-dependent muscle tone in the lower limbs (Lower Limb Muscle Tone-6 \[LLMT-6\]) in participants with multiple sclerosis (MS). LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS)-transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis.
   Filippini G, Minozzi S, Borrelli F, Cinquini M, et al · · 2022 · cited 41× · PMID 35510826 · DOI 10.1002/14651858.cd013444.pub2