Magnetic Resonance Imaging Study of JM-4 in Multiple Sclerosis/Clinically Patients

• ClinicalTrials.gov Identifier: NCT03887065
• Recruitment Status: Unknown
• First Posted: March 22, 2019
• Last Update Posted: May 7, 2019
• Sponsor: Cook, Stuart, MD
• Information provided by (Responsible Party): Stuart Cook, MD, Cook, Stuart, MD

Study Description

Brief Summary:

This is a Phase 0/1 study of MS patients to determine the safety and potential efficacy of a novel, small human peptide designated as JM-4. The study will involve treatment for 5-7 days with JM-4 to determine the effects of Gadolinium(+) lesion number and volume in the brains of patients.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: JM-4	Early Phase 1

Detailed Description:

This study is the first study of JM-4 in patients with Multiple Sclerosis and is intended to show safety and potential efficacy in changing the size and/or number of GAD(+) lesions in the brain. The initial dose level of 1 mg/kg/ will establish safety of JM-4 treatment after 5-7 days of treatment via intravenous infusion over 30 minutes daily in3-5 patients with Multiple Sclerosis. MRI examinations will be conducted prior to treatment with JM-4 and 8 days after the initiation of treatment for the purpose of quantitating GAD(+) brain lesions. Once initial safety is established, the next group of 3-5 patients will receive 4 mg/kg/ of JM-4 daily for 5-7 days via 30 minute intravenous infusions, with MRI scans conducted prior to treatment and 8 days after the initial dose of JM-4. Once safety is established in this cohort of patients, a third group of patients may receive 9 mg/kg/ of JM-4 daily for 5-7 days via 30 minute infusions, with MRI scans conducted prior to the initial treatment and 8 days after the initial treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Magnetic Resonance Imaging 12 Day Study for Multiple Sclerosis/Clinically Isolated Syndrome Trial of JM-4 Novel Human Peptide
• Estimated Study Start Date: June 15, 2019
• Estimated Primary Completion Date: December 15, 2019
• Estimated Study Completion Date: March 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Starting dose; Three to five patients will receive a daily dose of 1 mg/kg JM-4 (in normal saline) delivered via intravenous infusion for no more than 30 minutes for up to 7 consecutive days.	Drug: JM-4; Novel small human peptide derived from erythropoietin
Experimental: Intermediate dose of JM-4; Three to five patients will receive a daily dose of 4 mg/kg of JM-4 (in normal saline) via intravenous infusion for no more than 30 minutes for up to 7 consecutive days.	Drug: JM-4; Novel small human peptide derived from erythropoietin
Experimental: High dose of JM-4; Three to five patients will receive a daily dose of 9 mg/kg of JM-4 (in normal saline) via intravenous infusion for no more than 30 minutes for up to 7 consecutive days.	Drug: JM-4; Novel small human peptide derived from erythropoietin

Outcome Measures

Primary Outcome Measures :

1. Number of patients with treatment-related adverse events [ Time Frame: From initial dose through 8 days after initiation of dosing ]
   To determine the incidence of adverse events and any abnormal laboratory values
2. Change in GAD(+) brain lesions measured via MRI scan [ Time Frame: From initial dose through 8 days after initiation of dosing ]
   Measurement of the number and size of GAD(+) brain lesions from baseline to post-dosing 8 days after initiation of treatment

Secondary Outcome Measures :

1. Changes in the ability of patients to complete a timed 25-foot walk [ Time Frame: From initial dosing through 8 days post-initiation of dosing ]
   To determine changes in timed 25 foot walk prior to treatment or 8 days after treatment
2. Treatment-induced changes in Expanded Disability Status Score in patients [ Time Frame: Prior to initial dose through 8 days post-initial treatment ]
   Measurement of Expanded Disability Status scores in patients prior to treatment and after completion of treatment
3. Changes in neurological exam [ Time Frame: Prior to initial dose through 8 days post-initial treatment ]
   Neurological examination of patients to check for optic nerve changes and vision changes

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Definite MS (McDonald criteria) or CIS
• GAD(+) MRI brain lesion on screening exam, with or without clinical activity followed by a baseline MRI
• EDSS of 0-5.5 inclusive
• Weight of 40-115 kg
• Females must be post-menopausal or surgically sterilized or use a hormonal contraceptive, intra-uterine device or diaphragm with spermicide during the study
• Not be pregnant or breast feeding
• Males must be willing to use contraception during each day of the study
• Be willing to comply with study procedures and protocols for the duration of the study
• Voluntarily provide informed consent
• Be wiling and physically able to attend the study center as required for all study screening and procedures

Exclusion Criteria:

• Taking Tysabri, Gilenya, Tecfidera, Aubagio, Ocrevus or other immunosuppressive drugs within the prior 3 months
• Received Mitoxantrone or Lemtrada at any time
• Consumption of corticosteroids within the past 30 days
• Current or less than 5 years prior malignancy (excluding basal cell or squamous cell skin cancer)
• Serious systemic disorder which might, in the opinion of the investigators, interfere with safety, compliance, treatment or evaluation of efficacy. Conditions would include but not be limited to significant cardiac, liver, kidney, lung or cerebrovascular disease, HIV, serious infections, serous psychiatric disease or poorly controlled diabetes mellitus
• aversion, intolerance or allergy to repeated MRI with gadolinium administration

Contacts and Locations

Contacts

Contact: Stuart Cook, MD; (201) 213-5052; cookstu@comcast.net

Sponsors and Collaborators

Cook, Stuart, MD

Investigators

• Principal Investigator: Stuart Cook, MD; VA Medical Center

More Information

• Responsible Party: Stuart Cook, MD, Professor, Cook, Stuart, MD
• ClinicalTrials.gov Identifier: NCT03887065
• Other Study ID Numbers: JM-4-001
• First Posted: March 22, 2019
• Last Update Posted: May 7, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases