Study of Safety and Efficacy of MGCND00EP1 as an Add on Treatment in Children and Adolescents With Resistant Epilepsies

NCT04406948 | Withdrawn Phase 2

• 1 other identifier: MGC-002
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

EudraCT: 2018-003887-29 Objective:To evaluate the safety and efficacy of: MGCND00EP1 from MGC PHARMACEUTICALS d.o.o. Study Design: Randomized, double blind, placebo controlled parallel grouped study Sample Size: 103 subjects Study Population: Children from 1 year to 18 years of age Comparator Product :Placebo solution, oral IMP Product : MGCND00EP1 (each ml of solution containing 100 mg of cannabidiol and 5 mg of (-)-trans-Δ9- tetrahydrocannabinol as active substance) from MGC PHARMACEUTICALS D.O.O. According to dosing scheme up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller) for 6 weeks titration and 6 weeks of treatment, oral administration

Conditions

Resistant Epilepsy, Drug; Adolescent Epilepsy; Children Epilepsy; Children and Adolescents With Resistant Epilepsies

Keywords

epilepsy; resistant epilepsy; adolescents; children

Outcome Measures

Primary Outcomes (2)

• The proportion of patients showing a >50% reduction in frequency of seizures at week 12 of the study, in the treatment versus placebo groups

  study drug overall efficiency as a seizure reducing treatment compared to placebo group

  12 weeks

• Change in number of epileptic seizures as documented by patient diaries (Visit 2 level compared to Visit 3 level and Visit 4) in treatment and placebo group.

  study drug overall efficiency as a seizure reducing treatment

  16 weeks

Secondary Outcomes (8)

• The incidence of adverse events will be summarized by organ class, severity and duration on weeks 12 and 18 of the study.

  12-18 weeks

• Any change in physical examination, vital signs, lab tests results, ect will be collected and analyzed.

  18 weeks

• Change in duration of epileptic seizures as documented by patient diaries (Visit 2 level compared to Visit 3 level and Visit 4 level compared to Visit 2 level) by treatment group.

  12-18 weeks

• Change in score from Quality of Life in Childhood Epilepsy Questionnaire 55 (QOLCE-55 questionnaire) scoring 0-100 points, higher scoring indicates better condition. scoring will be compared between Visit 2 level and Visit 4 level.

  18 weeks

• Change in Clinical Global Impressions Scale (CGI scale) scoring 1-7 points, low scoring indicates better condition. Visit 2 level compared to Visit 4 level by treatment group.

  18 weeks

Study Arms (2)

MGCND00EP1

EXPERIMENTAL

Participants who will assigned to receive add on MGCND00EP1 will receive carrier oil containing THC and CBD in ratio 20:1, (10% of cannabidiol and 0.5 % and (-)-trans-Δ9-tetrahydrocannabinol) . Titration Dose: 1 to 2 mg/kg body weight/day. dose will be increased every week by 2 mg/kg body weight/day up to a maximum 25 mg/kg body weigh/day or maximum daily dose 800 mg (the smaller of those 2 values) (divided into two daily doses). After titration, patients will be receiving a stable maintenance dose of IMP (up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller)) for 6 weeks period. During forth treatment period participants will commence a 2 weeks down-titration taper period, followed by 4 weeks observational follow up period of previous standard AE treatment without IMP.

Drug: MGCND00EP1; Diagnostic Test: ECG; Diagnostic Test: EEG; Diagnostic Test: Blood and urine collection

PLACEBO

PLACEBO COMPARATOR

Participants who are assigned to receive add on PLACEBO will be administered the carrier oil (without the active ingredients). Titration Dose: 1 to 2 mg/kg body weight/day. dose will be increased every week by 2 mg/kg body weight/day up to a maximum 25 mg/kg body weigh/day or maximum daily dose 800 mg (the smaller of those 2 values) (divided into two daily doses). After titration, patients will be receiving a stable maintenance dose of IMP (up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller)) for 6 weeks period. During forth treatment period participants will commence a 2 weeks down-titration taper period, followed by 4 weeks observational follow up period of previous standard AE treatment without IMP.

Drug: Placebo; Diagnostic Test: ECG; Diagnostic Test: EEG; Diagnostic Test: Blood and urine collection

Interventions

MGCND00EP1 DRUG

Patients will take cannabis oil during the study

Also known as: Cannabis oil

MGCND00EP1

Placebo DRUG

Patient will take carrier oil during the study

PLACEBO

ECG DIAGNOSTIC_TEST

A standard 12-lead ECG will be recorded using digital ECG recording equipment provided to the investigational site. The ECG has to be performed prior to laboratory samplings at time points indicated in the Schedule of Assessments. The ECG recording will be reviewed by investigator and case of need consultation with cardiologist will be performed. The investigator has the final decision on the clinical significance of the ECG results.

MGCND00EP1; PLACEBO

EEG DIAGNOSTIC_TEST

An EEG is an electrophysiological monitoring method that records the electrical activity and measures voltage fluctuations resulting from ionic current within the neurons of the brain. In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a period of time.

MGCND00EP1; PLACEBO

Blood and urine collection DIAGNOSTIC_TEST

safety blood tests - hematology\\blood count and biochemistry standard blood tests urinalysis - urine test analysis

Also known as: blood tests

MGCND00EP1; PLACEBO

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient has documented clinically confirmed diagnosis of epilepsy;
• Patient did not respond to at least 2 AED's therapy given in adequate doses;
• Patients current therapy is considered inadequate (not completely controlled by AEDs); patients had four or more countable seizures with a motor component per 4 week period;
• Patient is aged 1 year - 18 years inclusive at screening age;
• Patient took one or more AEDs treatment at dose which has been stable for at least 4 weeks before enrolment;
• Females of childbearing potential can only participate in the study if willing to use acceptable, effective methods of contraception during the trial and for three month after end of trial participation as defined in point 7.10 of this protocol;
• Patient/parent is able to read/understand informed consent.
• Male patients must either be surgically sterile or he and his female spouse/partner who is of childbearing potential must be willing to use highly effective methods of contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study.
• All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation (VNS) were stable for four weeks prior to screening and participants were willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not counted as an AED.

You may not qualify if:

• Known history or presence of clinically significant unstable medical condition other that epilepsy which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• Known history or presence of serious cardiovascular disease
• Known or suspected history or family history of: schizophrenia, or other psychotic illness, severe personality disorder or other significant psychiatric disorder.
• Known or suspected allergy hypersensitivity or idiosyncratic reaction to cannabinoids or any other drug substances with similar activity or to any of the excipients of the IMP.
• Participant has clinically relevant abnormalities in the 12-lead electrocardiogram measured at screening or randomisation.
• Patients were currently using or had in the past used recreational or medicinal cannabis or synthetic CBD based medications or preparations within last 3 months or had previous or current treatment with cannabis-based therapy within last 3 months.
• History of drug or alcohol addiction requiring treatment.
• History of malabsorption within the last year or presence of clinically significant gastrointestinal disease or surgery that may affect drug bioavailability, including but not limited to cholecystectomy.
• Presence of hepatic or renal dysfunction.
• Females who: are pregnant (serum hCG level consistent with pregnancy diagnosis); or are lactating;
• Participation in a clinical trial that involved administration of an investigational medicinal product within 90 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results;
• Participant has clinically significant abnormal laboratory values (e.g. liver enzymes);
• Participant has clinically significant findings from a physical examination (fever);
• In case of ketogenic diet or VNS; the diet need to be stable for at least 4 weeks, and VNS ramping needs to be stable at least 12 weeks before enrolment.

Sponsors & Collaborators

• MGC Pharmaceuticals d.o.o: lead

Study Sites (2)

Schneider Children's Medical Center of Israel

Petach Tikvah, Central District, 4920235, Israel

Location

University Children's Hospital Ljubljana University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

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Related Links

• nice.org-( dne: 14.februarja 2016)

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy

Interventions

nabiximols; Electrocardiography; Electroencephalography; Blood Specimen Collection; Urine Specimen Collection; Hematologic Tests

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Diagnostic Techniques, Neurological; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rubi Zomer

  MGC Pharmacuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Treatment with current antiepileptic therapy 28 days - Various combinations of anti-epileptic (AE) medications * Add on treatment 42 days (6 weeks) - titration period - MGCND00EP1 or placebo in addition to AE medications. * Add on treatment 42 days (6 weeks) Maintenance stable treatment period - MGCND00EP1 or placebo in addition to AE medications * Add on treatment 14 days (2 weeks)- taper - down titration period - MGCND00EP1 or placebo in addition to AE medications * Follow up 28 days - Standard/ previous AE treatment

Study Record Dates

• First Submitted: May 17, 2020
• First Posted: May 29, 2020
• Study Start: May 30, 2024
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1); IL (1)