A phase II randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of an oral solution of 9-Δ tetrahydrocannabinol/cannabidiol (THC/CBD) in multiple sclerosis patients with chronic neuropathic pain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ferraz Lynce Especialidades Farmaceuticas S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Sep 2025 → ongoing

Decision date (initial)

2025-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ferraz Lynce · FERRAZ, LYNCE, ESPECIALIDADES FARMACÊUTICAS, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of an oral solution of THC:CBD (25 mg + 25 mg/mL) in relieving chronic neuropathic pain due to MS, after 4 weeks of optimized treatment compared with placebo

Secondary objectives 9

1. To evaluate the efficacy of an oral solution of THC:CBD (25 mg + 25 mg/mL) in relieving chronic neuropathic pain due to MS after 12 weeks of optimized treatment
2. To evaluate the efficacy of an oral solution of THC:CBD (25 mg + 25 mg/mL) in relieving spasticity symptoms after 4 and 12 weeks of optimized treatment
3. To evaluate the impact of an oral solution of THC:CBD (25 mg + 25 mg/mL) on sleep quality and disturbances, after 4 and 12 weeks of optimized treatment
4. To evaluate the impact of an oral solution of THC:CBD (25 mg + 25 mg/mL) on health status, after 12 weeks of optimized treatment
5. To evaluate the impact of an oral solution of THC:CBD (25 mg + 25 mg/mL) on overall impression of change after 4 and 12 weeks of optimized
6. To evaluate the impact of an oral solution of THC:CBD (25 mg + 25 mg/mL) on disability, after 4 and 12 weeks of optimized treatment
7. To evaluate the impact of an oral solution of THC:CBD (25 mg + 25 mg/mL) on motor coordination, after 4 and 12 weeks of optimized treatment
8. To evaluate the pharmacokinetics of an oral solution of THC:CBD (25 mg + 25 mg/mL) in MS patients following a 25 mg + 25 mg/mL
9. To evaluate the safety and tolerability of an oral solution of THC:CBD (25 mg + 25 mg/mL) during the treatment period

Conditions and MedDRA coding

Chronic neuropathic pain due to multiple sclerosis (MS)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Infarmed

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Native Portuguese speakers who provided free written informed consent prior to any procedure required by the study.
2. Willing to accept and comply with all study procedures and restrictions, including not driving motorized vehicles from first administration until EoS or safety follow-up
3. Male or female subjects with age between 18 to 65 years old, inclusive at the time of signing the informed consente
4. No clinically relevant abnormalities on vital signs
5. No clinically relevant abnormalities on 12-lead ECG
6. No clinically relevant abnormalities on clinical laboratory tests
7. Diagnosis of MS for more than 6 months, according to the 2017 revised McDonald criteria, including any subtype of MS (Relapsing-Remitting MS, Secondary Progressive MS, Primary Progressive MS, and Progressive-Relapsing MS)
8. Chronic neuropathic pain due to MS for at least 6 months
9. Patients refractory or intolerante to at least one drug for the treatment of chronic neuropathic pain.
10. Stable dose of Disease Modifying Therapies (DMTs) for at least 6 months and willingness to maintain this regimen for the duration of the study
11. Stable regimen of concomitant medications and non-pharmacological therapies for at least 4 weeks prior to screening visit and willing to maintain these regimens for the duration of the study
12. A female patient is eligible if she meets one of the following criteria: - is of non-childbearing potential (refer to Section 6.4.- Contraception Requirements for the criteria for non-childbearing potential status); or - is of childbearing potential and agrees to use an highly effective contraceptive method (refer to Section 6.4.- Contraception Requirements for a list of accepted methods) from admission to study period until at least 3 months after the last investigational product administration. – Women choosing to use a hormonal contraceptive should also use a barrier method (condom).
13. A male patient who is sexually active with a female partner of childbearing potential (pregnant or non-pregnant) must use contraception (condom) from admission until at least 3 months following the last investigational product administration
14. A male patient must ensure that his non-pregnant female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception (see Section 6.4.)
15. A male patient must be willing not to donate sperm from admission until 3 months days following the last investigational product administration

Exclusion criteria 33

1. Pain symptom that could clearly be attributed to reasons other than neuropathic pain, as judgment of principal Investigator
2. Baseline QTcF interval >450 msec if man or >470 msec if woman, or <350 msec
3. Systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <60 mmHg
4. Known or suspected personal or family history of schizophrenia or other psychotic disorders, history of severe personality disorders, significant anxiety or depression (e.g., Hospital Anxiety and Depression Scale [HADS] ≥11), or any other significant psychiatric condition.
5. Estimated renal creatinine clearance (CLCr) <60 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula
6. Participation in another clinical trial within 30 days prior to screening
7. Any condition that, in the opinion of the Investigator may either put the subject at risk, would interfere with the patient's ability to comply with the study protocol or give informed consent
8. Average NRS pain score <4 points during the screening period (mean of the last four available ratings in the 7 days prior to the visits).
9. New pain treatments or significant changes in existing pain treatments during the screening period
10. If WOCBP, positive pregnancy test in urine
11. Any other condition that the Investigator considers to render the patient unsuitable for the study period
12. Known or suspected hypersensivity to cannabinoids or any of the excipients of the study medication.
13. Patients who did not attain clinical benefit by the end of the treatment period
14. Veins unsuitable for intravenous puncture on either arm
15. Unable to attain the 25 mg + 25 mg dose
16. History of epilepsy
17. Use of the following medications , within 30 days prior to enrolment on the extension period: - inibitors of CYP3A4 isoenzymes such as macrolides (e.g., clarithromycinand erythromycin), antifungals (e.g., itraconazole, fluconazole, ketoconazole, and miconazole), HIV protease inibitors (e.g.ritonavir), and verapamil. – inducers of CYP3A4 such as carbamazepine, fenobarbital, phenytoin, rifampicin, efavirenz, rifabutin, and troglitazone. – strong inibitors of CYP2C9 (e.g. amiodarone, clopidogrel, fluconazole, fluoruracil, metronidazole, sulfamethoxazole, and valproic acid, St. John’s wort). – strong inducers of CYP2A9 (e.g., barbiturates, carbamazepine,phenytoin, rifampicin, rifabutin, and St. John’s wort). – strong inhibitors of CYP2C19 (e.g., chloramphenicol, clopidogrel, efavirenz, esomeprazole, fluconazole, fluoxetine, fluvoxamine, isoniazid, modafinil, omeprazole, oxcarbazepine, voriconazole). – strong inducers of CYP2C19 (e.g., barbiturates, carbamazepine, phenytoin, primidone, rifampicin, St. John’s wort).
18. Known or suspected history of alcohol or substance abuse
19. Any clinically significant cardiovascular or respiratory conditions that could be exacerbated by THC:CBD use
20. Patients on warfarin, insulin and/or sulfonylureas.
21. Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months
22. If woman of childbearing potential (WOCBP), positive pregnancy test Se mulher com potencial para engravidar (WOCBP), teste de gravidez positivo.
23. Patients with severe unstable cardiovascular disease
24. Use of cannabinoids or cannabinoid-based medications within 30 days prior to screening and unwillingness to abstain for the duration for the study
25. Posed a significant risk of a suicide attempt based on history or the Investigator’s judgment; answer “yes” to Suicidal Ideation items 4 or 5 on the C-SSRS for current or past 3 months on the “Baseline/Screening version”; have had suicidal behavior in his/her lifetime as measured by the C-SSRS; or are at imminent risk of suicide or violent behavior based on the Investigator’s clinical assessment or the C-SSRS assessment of lifetime suicidal ideation or behavior.
26. Patients with liver failure (Child-Pugh B or C)
27. Scheduled elective surgery or other procedures, which require general anaesthesia during the study
28. Use of the following medications, within 30 days prior to screening: - systemic corticoids, non-steroidal anti-inflammatory drugs other than those used at stable doses for conditions unrelated to neuropathic pain. - immunomodulatory or immunosuppressive therapies (other than DMTs)
29. Use of other concomitant medications and non-pharmacological therapies that may lead to patient non-enrolment in this study, according to Investigator judgment. * Unless therapeutic drug monitoring is available, digoxin, lithium, phenytoin, carbamazepine, valproate, clobazam, and theophylline will not be allowed.
30. Use of concomitant medications not on stable regímen for at least 4 weeks prior to screening visit or with a regímen that is expected to change during the study.
31. If woman, she is breast-feeding
32. Positive result in urine ethanol test.
33. Patients who did not take the last four doses of IMP as per protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: Change in pain intensity as measured by the Numeric Rating Scale (NRS 0-10) between baseline (Day 1) and 4 weeks of optimized treatment (corresponding to Week 6 visit); the mean of the last four available ratings in the 7 days prior to a study visit will be considered.

Secondary endpoints 16

1. Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment
2. Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment
3. Efficacy: Change in pain intensity as measured by the NRS 0-10 between baseline (Day 1) and 12 weeks of optimized treatment
4. Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment
5. Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment
6. Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 4 weeks of optimized treatment.
7. Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 12 weeks of optimized treatment.
8. Efficacy: Change in spasticity symptom measured by the NRS 0-10 between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment (0: No spasticity - The patient experiences no increase in muscle tone or involuntary muscle spasms; 10: Worst possible spasticity - The patient experiences extreme muscle stiffness, severe spasms, and significant difficulty with movement)
9. Efficacy: Change in Pittsburgh Sleep Quality Index (PSQI) component scores and global score between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment
10. Efficacy: Change in EuroQol 5-Dimensions, 5-Levels (EQ-5D-5L) index score between baseline (Day 1) and 12 weeks of optimized treatment
11. Efficacy: Change in EQ-5D-5L visual analogue scale (VAS) score between baseline (Day 1) and 12 weeks of optimized treatment
12. Efficacy: Proportion of patients reporting improvement in their condition with Patient Global Impression of Change (PGIC) scale after 4 and 12 weeks of optimized treatment
13. Efficacy: Change in the Expanded Disability Status Scale (EDSS) score between baseline (Day 1) and 4 weeks of optimized treatment and from baseline and 12 weeks of optimized treatment
14. Efficacy: Change in the Nine-Hole Peg test (NHPT) completion time from baseline (Day 1) and 4 weeks of optimized treatment and between baseline and 12 weeks of optimized treatment.
15. Efficacy: Reduction of at least a 30% Neuropathic Pain Symptom Inventory (NPSI) score after 4 and 12 weeks of optimized treatment.
16. Safety: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AE) leading to study discontinuation. Clinically relevant abnormalities in vital signs, 12-lead electrocardiogram (ECG) and laboratory parameters will be reported as AEs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ferraz Lynce Especialidades Farmaceuticas S.A.

Sponsor organisation

Ferraz Lynce Especialidades Farmaceuticas S.A.

Address

Estrada Consiglieri Pedroso 123, Queluz De Baixo Queluz De Baixo

City

Barcarena

Postcode

2734-501

Country

Portugal

Scientific contact point

Organisation

Ferraz Lynce Especialidades Farmaceuticas S.A.

Contact name

Sara Mota

Public contact point

Organisation

Ferraz Lynce Especialidades Farmaceuticas S.A.

Contact name

Sara Mota

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications