Multiple Sclerosis, Relapsing-RemittingPhase 3NCT03283397
A Phase IIIb, Multicenter, International Study to Evaluate the Efficacy, Safety and Tolerability of EK-12 in Patients With RRMS
A Phase 3 study testing EK-12 and INF beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Bosnalijek D.D at 1 site in Turkey (Türkiye).
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- EK-12 and INF beta-1a
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 301 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 26 Mar 2019to 1 Jul 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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).
- Use of inducers 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).
- Pregnancy or breastfeeding.
- Serum levels ≥3x upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening.
- Serum direct bilirubin ≥2x ULN at screening.
- Patients with clinically significant or unstable medical or surgical condition or any other condition that cannot be well controlled by the allowed medications permitted by the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, Electrocardiography (ECG), laboratory tests, MRI scan or chest X-ray. Such conditions may include:
- A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, de-compensated congestive heart failure, pulmonary embolism, coronary revascularization) that occurred during the past 6 months prior to randomization.
- Any acute pulmonary disorder
- A Central Nervous System (CNS) disorder other than MS that may jeopardize the patient's participation in the study, including such disorders that are demonstrated at the baseline MRI scan.
- Chronic renal insufficiency as Glomerular Filtration Rate (GFR) ≤60 mL/min at the screening visit.
- Patients who use haloperidol or dopamine antagonists.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Kocaeli University, Faculty of Medicine, Department of Neurology
Kocaeli
About this study
Official title: A Phase IIIb, Multi-center, International, Randomized, Assessor-blind, Active-controlled Parallel Arm Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Neuropeptide Combination of Metenkefalin and Tridecactide (EK-12) in Comparison to Interferon Beta-1a (REBIF®) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
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
- Being tested
- EK-12, INF beta-1a
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EK-12Drug
10 mg metenkefalin acetate + 2 mg tridecactide acetate in 2 mL 0.9 % NaCl solution.
INF beta-1aDrug
Active substance is INF beta-1a, 44 mcg in 0.5 mL solution
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: INF beta-1a |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
Secondary outcomes (4)
EDSS score
slowing the progression of disability, assessed by EDSS score
Measured: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
clinical attacks
reducing the rate of clinical attacks
Measured: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
T2 lesions
reducing the total number of new and/or enlarging T2-hyperintense lesions
Measured: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
T1 lesions
reducing the total number of Gd (+) T1 lesions on MRI scan
Measured: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start26 Mar 2019
- Primary completion1 Jul 2023
- Study completion1 Jul 2023
Why it stopped: During the Covid-19 pandemic, the study was unable to enrol further patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to one of the two treatment arms and will be observed during the treatment period of 144 weeks
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 301 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bosnalijek D.D
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MonitorCRO
- Responsible party
- Sponsor
- Investigators
- Husnu Efendi, Prof, Principal investigator, Kocaeli University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03283397
- Sponsor's protocol ID
- RAP-CS-01
- Status last verified
- Feb 2023
- First submitted
- 12 Sep 2017
- Last updated
- 13 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb, Multi-center, International, Randomized, Assessor-blind, Active-controlled Parallel Arm Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Neuropeptide Combination of Metenkefalin and Tridecactide (EK-12) in Comparison to Interferon Beta-1a (REBIF®) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
- ClinicalTrials.gov ID
- NCT03283397
- Acronym / sponsor ID
- RAP-CS-01
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: During the Covid-19 pandemic, the study was unable to enrol further patients.
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Bosnalijek D.DIndustry (pharma, biotech, devices)
- Collaborators
- MonitorCRO
- Study start
- 26 Mar 2019 (actual)
- Primary completion
- 1 Jul 2023 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 14 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized to one of the two treatment arms and will be observed during the treatment period of 144 weeks
| Arm | Type | Receives |
|---|---|---|
| EK-12 | Experimental | Drug: EK-12This arm will be treated with 12 mg EK-12 in 2 mL 0.9 % NaCl solution (SC, three times per week) for 144 weeks |
| INF Beta-1a | Active comparator | Drug: INF beta-1aThis arm will be treated with 44 mg INF Beta-1a in 0.5 mL solution (SC, three times per week) for 144 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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:
- 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).
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EK-1210 mg metenkefalin acetate + 2 mg tridecactide acetate in 2 mL 0.9 % NaCl solution. | Drug | EK-12 |
| INF beta-1aActive substance is INF beta-1a, 44 mcg in 0.5 mL solution | Drug | INF Beta-1a |
Primary outcome
Superiority of efficacy of EK-12 to interferon beta-1a in patients with RRMS
Time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
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.
4 secondary outcomes
EDSS score
Time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
clinical attacks
Time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
T2 lesions
Time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
T1 lesions
Time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
Results and safety
The study was stopped early (reason given: During the Covid-19 pandemic, the study was unable to enrol further patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Husnu Efendi, Prof principal investigator
Kocaeli University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EK-12 and INF beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Bosnalijek D.D at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: During the Covid-19 pandemic, the study was unable to enrol further patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Superiority of efficacy of EK-12 to interferon beta-1a in patients with RRMS (time frame: weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024.