A Phase IIIb, Multicenter, International Study to Evaluate the Efficacy, Safety and Tolerability of EK-12 in Patients With RRMS

NCT03283397 | Terminated Phase 3 DMC

• 1 other identifier: RAP-CS-01
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis is a chronic autoimmune, inflammatory neurological disease of the central nervous system. It is the most common disabling neurologic disease of young people. This study is planned for the evaluation of efficacy, safety and tolerability of neuropeptide combination of metenkefalin and tridecactide (EK-12) as compared to INF beta-1a (REBIF®) in patients with RRMS. The primary objective of this study is to prove the superiority of efficacy of neuropeptide combination of metenkefalin and tridecactide (EK-12) compared to INF beta-1a (REBIF®) in patients with RRMS on the basis of annualized protocol defined relapse rate by 144 weeks.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Superiority of efficacy of EK-12 to interferon beta-1a in patients with RRMS

  The primary objective of this study is to prove the superiority of efficacy of neuropeptide combination of metenkefalin and tridecactide (EK-12) compared to interferon beta-1a (INF beta-1a, 44 mcg, REBIF®) in patients with RRMS on the basis of annualized protocol defined relapse rate (ARR) by 144 weeks.

  weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

Secondary Outcomes (4)

• EDSS score

  weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

• clinical attacks

  weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

• T2 lesions

  weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

• T1 lesions

  weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

Study Arms (2)

EK-12

EXPERIMENTAL

This arm will be treated with 12 mg EK-12 in 2 mL 0.9 % NaCl solution (SC, three times per week) for 144 weeks

Drug: EK-12

INF Beta-1a

ACTIVE COMPARATOR

This arm will be treated with 44 mg INF Beta-1a in 0.5 mL solution (SC, three times per week) for 144 weeks

Drug: INF beta-1a

Interventions

EK-12 DRUG

10 mg metenkefalin acetate + 2 mg tridecactide acetate in 2 mL 0.9 % NaCl solution.

EK-12

INF beta-1a DRUG

Active substance is INF beta-1a, 44 mcg in 0.5 mL solution

INF Beta-1a

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients from both genders with a confirmed and documented diagnosis of MS as defined by the Revised McDonald criteria (2010), with relapse onset disease or a relapsing-remitting disease course, between 18 and 55 years of age at screening (inclusive).
• Ambulatory patients with EDSS score of 0 to 4.5 at both screening and randomization visits.
• Patients who meet one of the following disease activity criteria:
• At least 1 documented relapse within the last 12 months prior to screening or;
• At least 1 documented relapse occurred within the last 24 months prior to screening and documented evidence of at least 1 Gadolinium Enhancing (GdE) lesion on brain MRI scan within the last 12 months prior to randomization.
• Patients with a confirmed stable neurological condition, who are relapse-free and not on a corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or per os (PO)\] or adrenocorticotrophic hormone (ACTH) treatment, at least 30 days prior to randomization.
• Women of child-bearing potential (e.g. women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication. Acceptable methods of birth control include: intrauterine devices, barrier method (condom with spermicide or diaphragm with spermicide) and hormonal methods of birth control (e.g. oral contraceptive, contraceptive patch, and long-acting injectable contraceptive).
• Patients must be able to sign and date a written Informed Consent Form (ICF) prior to entering the study.
• Patients must be willing and able to comply with the study protocol requirements for the duration of the study

You may not qualify if:

• Patients with progressive forms of MS.
• Patients with disease duration of ≥10 years.
• Inability to complete an MRI examination. Contraindications for MRI examination include but are not restricted to overweight, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.
• Patients with neuromyelitis optica (NMO) or NMO spectrum disorders.
• Use of experimental or investigational drugs and/or participation in drug clinical studies within 6 months prior to randomization.
• Use of immunosuppressive agents or cytotoxic agents, including cyclophosphamide within 6 months prior to randomization.
• Use of either of the following agents within 2 years prior to randomization: natalizumab, rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.
• Use of teriflunomide within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization.
• Previous treatment with glatiramer acetate, interferon-beta (either 1a or 1b), fingolimod, dimethyl fumarate or intravenous immunoglobulin (IVIG) within 2 months prior to randomization.
• Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 30 days prior to randomization.
• Previous use of mitoxantrone, cladribine, or alemtuzumab.
• Previous use of EK-12.
• Previous total body irradiation or total lymphoid irradiation.
• Previous stem cell treatment, autologous bone marrow transplantation or allogeneic bone marrow transplantation.
• Use of moderate/strong inhibitors of CYP3A4 within 2 weeks prior to randomization (Appendix VII provides a list of such medications that are disallowed prior to and during the study).

Sponsors & Collaborators

• Bosnalijek D.D: lead
• MonitorCRO: collaborator

Study Sites (1)

Kocaeli University, Faculty of Medicine, Department of Neurology

Kocaeli, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

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

Study Officials

• Husnu Efendi, Prof

  Kocaeli University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A blinded examining neurologist/assessor will conduct neurological examinations, relapse and EDSS evaluations at each site. Treating investigators will not be blinded to the study treatment. Additionally, blinded evaluation of MRI scans will be performed at a central reading facility in which, anonymized and standardized images of patient with RRMS will be read by a treatment blinded assessor and data will be implemented in a post-hoc analysis for selected time-points.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to one of the two treatment arms and will be observed during the treatment period of 144 weeks

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: March 26, 2019
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: August 13, 2024

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)