Clinical trial NCT04909502: Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Relapsing Forms of Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Relapsing Forms of Multiple Sclerosis
Keywords: Multiple Sclerosis
Nervous System Diseases
Demyelinating Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Relapsing Forms of Multiple Sclerosis
Relapsing Remitting Multiple Sclerosis
Relapsing Secondary Progressive Multiple Sclerosis
Lead sponsor: Emerald Health Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-06-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will initially be conducted with 2 treatment arms starting in parallel. Patients will initially receive a 25 mg OD or a 25 mg BID dose. After 28 days, each patient will increase to a 50 mg OD or 50mg BID dose level, respectively, if deemed to be safe by the investigator.
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Incidence and severity of Treatment Emergent Adverse Events
timeFrame: 168 days (24 weeks)
Secondary outcomes:
measure: Brain lesion activity measured by MRI
timeFrame: 168 days (24 weeks)
measure: Disease progression measured by MS Functional Composite (MSFC)
timeFrame: 168 days (24 weeks)
measure: Disease progression measured by Expanded Disability Status Scale (EDSS)
timeFrame: 168 days (24 weeks)
measure: Disease progression measured by Symbol Digit Modalities Test (SDMT)
timeFrame: 168 days (24 weeks)
measure: Disability status measured by MS Functional Composite (MSFC)
timeFrame: 168 days (24 weeks)
measure: Disability status measured by Expanded Disability Status Scale (EDSS)
timeFrame: 168 days (24 weeks)
measure: Disability status measured by Symbol Digit Modalities Test (SDMT)
timeFrame: 168 days (24 weeks)
measure: Time to first relapse
timeFrame: 168 days (24 weeks)
measure: Preliminary Annualized Relapse Rate (ARR)
timeFrame: 168 days (24 weeks)
measure: Percent of patients who experience a relapse
timeFrame: 168 days (24 weeks)
measure: Proportion of patients who remain qualified as relapse-free
timeFrame: 168 days (24 weeks)
measure: Change in blood levels of neurofilament light chain (NfL)
timeFrame: Baseline, 28 Days, 56 Days, 84 Days, 112 Days, 140 Days, 168 Days
Other outcomes:
measure: Microstructural analysis and assessment of potential remyelination measured by Magnetization Transfer Ratio (MTR)
timeFrame: 168 days (24 weeks)
measure: Assessment of white matter diffusivity and integrity measured by Diffusion Tensor Imaging (DTI)
timeFrame: 168 days (24 weeks)
measure: VCE-004.8 plasma trough levels for all patients
timeFrame: 197 Days (28 weeks)
measure: Pharmacokinetic profile of VCE-004.8 in terms of maximum observed plasma concentration (Cmax)
timeFrame: Day 1 (pre-dose) and at 0.5, 1, 2, 3, 4 and 6 hours post-dose on Day 1 and Day 28
measure: Pharmacokinetic profile of VCE-004.8 in terms of area under the plasma concentration-time curve (AUC)
timeFrame: Day 1 (pre-dose) and at 0.5, 1, 2, 3, 4 and 6 hours post-dose on Day 1 and Day 28
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates
state: Alabama
city: Fullerton
country: United States
facility: Fullerton Neurology and Headache Center
state: California
city: Port Orange
country: United States
facility: Accel Research Sites - Brain and Spine Institute of Port Orange
state: Florida
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
Study officials:
References: