Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Relapsing Forms of Multiple Sclerosis

Relapsing Forms of Multiple Sclerosis Clinical Trial

Official title:

A Phase IIa, Open-label, Multicentre Dose-Finding Trial in Patients With Relapsing Forms of Multiple Sclerosis (RMS) to Evaluate the Safety, Tolerability and Preliminary Efficacy of EHP-101

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04909502
• Other study ID #: EHP-101-MS02
• Status: Suspended
• Phase: Phase 2
• Start date: October 19, 2021
• Est. completion date: April 2024

Study information

• Verified date: April 2022
• Source: Emerald Health Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of EHP-101 in adult subjects with Relapsing Forms of Multiple Sclerosis (RMS).

Description:

An interventional, open label, randomized design will be used to test safety, tolerability, pharmacokinetics, and preliminary efficacy of EHP-101 in 50 patients ≥ 18 and ≤ 55 years of age with documented RMS. There will be a screening period of up to 28 days, 168 days treatment period, and 28 days follow-up.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 50
• Est. completion date: April 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male and female adults aged 18 to 55 years at the time of consent;
• Confirmed diagnosis of MS according to the revised 2017 McDonald criteria;
• Relapsing forms of MS (RMS) including Relapsing-Remitting MS (RRMS) and active Secondary Progressive MS (SPMS);
• Patients must have experienced at least 1 of the following within 12 months prior to Visit 1: an acute clinical relapse, gadolinium-enhancing T1 lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI;
• Neurologically stable with no evidence of clinical relapse of MS or corticosteroid treatment within 28 days prior to the first investigational product administration;
• Naïve to prior MS treatment or discontinuing current MS treatment due to (1) intolerability, (2) laboratory abnormalities, (3) current treatment perceived by the patient to be ineffective, (4) patient preference, or (5) based on investigator judgement to switch MS therapy;
• An EDSS score of 0 to 6.0 (inclusive) at screening and enrolment visit;
• Willing and able to provide informed consent and capable of understanding and complying with the protocol.

Exclusion Criteria:

• Primary progressive MS (PPMS) or non-active secondary progressive MS (SPMS);
• Relapse during the 28 days prior to first investigational product administration;
• Total lymphoid irradiation, T-cell or T-cell receptor vaccination, total body irradiation, or total lymphoid irradiation at any time;
• Treatment with alemtuzumab, mitoxantrone, cyclophosphamide or cladribine at any time;
• MS treatment that may impact the efficacy or safety assessment defined as follows:

1. 52 weeks or less prior to first investigational product administration:

Immunosuppressant agents (e.g., cyclosporine, methotrexate, mycophenolate)

2. 36 weeks or less prior to first investigational product administration: CD20 depletion therapies such as rituximab, ocrelizumab, ofatumumab or others. Condition for inclusion of patients who had CD20 depletion therapies more than 36 weeks prior to the first investigational product administration: may only be included if there is no clinically relevant B cell depletion and possible safety risk to patients based on the Investigator's opinion.

3. 12 weeks or less prior to first investigational product administration:

natalizumab

4. 8 weeks or less prior to first investigational product administration:

dimethyl-fumarate fingolimod

5. 4 weeks or less prior to first investigational product administration:

corticosteroids intravenous immunoglobulin (IVIG) ozanimod, siponimod, or ponesimod glatiramer acetate interferons

6. 2 weeks or less prior to first investigational product administration:

teriflunomide. Subject must exhibit no active agent in serum levels; cholestyramine or activated charcoal washout may be used to achieve this;

• Any one of the following values for laboratory test at screening:

1. Haemoglobin < 9 g/dL;

2. Neutrophils < 1.0 x 10^9/L;

3. Platelets < 75 x 10^9/L;

4. Serum transaminases > 2.0 x upper limit of normal;

5. Total bilirubin = 1.5 x upper limit of normal;

6. Thyroid-stimulating hormone level >10% above of the upper limit of normal;

7. Estimated glomerular filtration rate =60 mL/min/1.73m2 (using the Cockcroft-Gault equation);

8. Lymphocytes < 1 × 10^9/L;

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Forms of Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• EHP-101 25 mg OD
25 mg OD during the first 28 Days of the trial
• EHP-101 25 mg BID
25 mg BID during the first 28 Days of the trial
• EHP-101 50 mg OD
After 28 Days of treatment with 25 mg OD, patients will escalate to 50 mg OD up to the end of the trial
• EHP-101 50 mg BID
After 28 Days of treatment with 25 mg BID, patients will escalate to 50 mg BID up to the end of the trial

Locations

Country	Name	City	State
Australia	St. Vincent's Hospital	Melbourne	Victoria
United States	North Central Neurology Associates	Cullman	Alabama
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Accel Research Sites - Brain and Spine Institute of Port Orange	Port Orange	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Emerald Health Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microstructural analysis and assessment of potential remyelination measured by Magnetization Transfer Ratio (MTR)		168 days (24 weeks)
Other	Assessment of white matter diffusivity and integrity measured by Diffusion Tensor Imaging (DTI)		168 days (24 weeks)
Other	VCE-004.8 plasma trough levels for all patients		197 Days (28 weeks)
Other	Pharmacokinetic profile of VCE-004.8 in terms of maximum observed plasma concentration (Cmax)		Day 1 (pre-dose) and at 0.5, 1, 2, 3, 4 and 6 hours post-dose on Day 1 and Day 28
Other	Pharmacokinetic profile of VCE-004.8 in terms of area under the plasma concentration-time curve (AUC)		Day 1 (pre-dose) and at 0.5, 1, 2, 3, 4 and 6 hours post-dose on Day 1 and Day 28
Primary	Incidence and severity of Treatment Emergent Adverse Events	This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments	168 days (24 weeks)
Secondary	Brain lesion activity measured by MRI		168 days (24 weeks)
Secondary	Disease progression measured by MS Functional Composite (MSFC)	The MSFC consists of three assessments of walking speed, processing speed and finger dexterity. The scores are combined to provide a Z-score (number of standard deviations away from mean of a normal population) with lower scores representing greater abnormality	168 days (24 weeks)
Secondary	Disease progression measured by Expanded Disability Status Scale (EDSS)	The EDSS is an ordinal scale used for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) and an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. The FSs are the Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral functions. The FSs and EDSS steps will be assessed in a standardized manner	168 days (24 weeks)
Secondary	Disease progression measured by Symbol Digit Modalities Test (SDMT)	The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution	168 days (24 weeks)
Secondary	Disability status measured by MS Functional Composite (MSFC)	The MSFC consists of three assessments of walking speed, processing speed and finger dexterity. The scores are combined to provide a Z-score (number of standard deviations away from mean of a normal population) with lower scores representing greater abnormality	168 days (24 weeks)
Secondary	Disability status measured by Expanded Disability Status Scale (EDSS)	The EDSS is an ordinal scale used for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) and an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. The FSs are the Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral functions. The FSs and EDSS steps will be assessed in a standardized manner	168 days (24 weeks)
Secondary	Disability status measured by Symbol Digit Modalities Test (SDMT)	The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution	168 days (24 weeks)
Secondary	Time to first relapse		168 days (24 weeks)
Secondary	Preliminary Annualized Relapse Rate (ARR)		168 days (24 weeks)
Secondary	Percent of patients who experience a relapse		168 days (24 weeks)
Secondary	Proportion of patients who remain qualified as relapse-free		168 days (24 weeks)
Secondary	Change in blood levels of neurofilament light chain (NfL)		Baseline, 28 Days, 56 Days, 84 Days, 112 Days, 140 Days, 168 Days

External Links

•   Sponsor website