Relapsing Remitting Multiple SclerosisPhase 2CEASE-MSNCT01717664
Proof of Concept Study of RHB-104 as Add-On Therapy to Interferon Beta-1a in Relapsing Remitting Multiple Sclerosis (RRMS)
A Phase 2 study testing RHB-104 in people with Relapsing Remitting Multiple Sclerosis, run by RedHill Biopharma Limited at 2 sites in Israel.
Trial summary
The investigators hypothesize that Mycobacterium avium paratuberculosis positive Relapsing Remitting MS subjects will have a greater response to Interferon beta-1a therapy plus RHB-104 than from Interferon beta-1a alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- RHB-104
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesIsrael
- Study dates
- Jun 2013to Jul 2016
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged ≥18 years
- Signed fully informed consent provided as per this protocol and willing to comply with the required scheduled assessments of the protocol.
- Diagnosis of relapsing-remitting multiple sclerosis (McDonald Criteria (2010)) with dissemination in time and space.
- Currently treated with a stable dose of Rebif®, or Avonex® for a minimum of 3 months duration prior to the screening visit.
- Active MS with history of at least one flare within the past 12 months or two flares in the past 24 months prior to screening.
- An Expanded Disability Status Scale (EDSS) of 6.0 or less at the screening visit.
- White blood cell count ≥ to 3.5x109.
- Subject agrees to use barrier contraceptive methods (i.e. diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository, or IUD from study enrolment through 6 weeks after last dose of study medication, unless subject is post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation, or has had a vasectomy. Subject agrees to appropriate contraception method though completion of study.
Who cannot join
- Treatment with any other biological therapies including but not limited to Interferon beta-1b, natalizumab, anti-TNF biologic agents, or other agents intended to reduce TNF ≤ 8 weeks prior to screening or within 5 half-lives of agent prior to screening, whichever is longer.
- Previous treatment with rifabutin and/or clofazimine.
- Previous treatment with amiodarone.
- Oral or parenteral antibiotics in the 4 weeks prior to screening. (Topical antibiotics are permitted.)
- Use of Methylprednisolone sodium succinate, prednisone, or any other corticosteroid during the 30 days prior to screening.
- Relapse within the 30 days prior to screening, or between screening and baseline.
Show all 37Show fewer
- Initiation or dose modification of 4-aminopyridine within 60 days of screening.
- Use of azathioprine, 6-mercaptopurine (6-MP), methotrexate, cyclosporine or mycophenolate (CellCept) within 8 weeks prior to screening.
- Use of glatiramer acetate, cyclophosphamide, or plasma exchange within 12 weeks prior to screening.
- Use of mitoxantrone within one year prior to screening.
- Any previous treatment with cladribine, T cell vaccine, or altered peptide ligand.
- Previous total body irradiation or total lymphoid irradiation.
- Treatment with any medication that causes QT prolongation or Torsades de Pointes within 7 days prior to initiation of study drug, including but not limited to: Cisapride, pimozide, astemizole, terfenadine, ergotamine, dihydroergotamine, quinidine, procainamide, disopyramide, sotalol, ibutilde, dofetilide, dronedarone, ondansetron or other 5-HT3 receptor agonists, citalopram dose greater than 20 mg/day, tolteridine and quinine.
- Treatment with the following medications within 7 days prior to initiation of study drug: colchicine, roflumilast, apixabin, latuda, nefazodone, buspirone, fluvoxamine, simvastatin, lovastatin, atorvastatin, amlodipine, diltiazem, felodipine, nifedipine, nitrendipine, nisoldipine, fluconazole, ketoconazole, voriconazole, St. Johns wort, grapefruit juice, antiretroviral agents, alprazolam, alfentanyl, aprepitant, aripiprazole, cyclosporine, boceprevir, carbamazepine, haloperidol, digoxin, propranolol, carvedilol, metoprolol, and estrogens.
- Adverse reaction or hypersensitivity to the study drug or any medications related to the study drug.
- Clinically significant abnormalities of hematology or chemistry at screening as confirmed by repeat testing based on investigator's discretion, including but not limited to, elevations greater than 2 times the upper limit of normal of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or creatinine clearance less than 60 ml/min at screening.
- Serum potassium, magnesium or calcium outside the normal reference range considered clinically significant by the investigator.
- Positive stool results for C. difficile.
- A positive serology for Hepatitis B, Hepatitis C or HIV at screening except for the following:
- If positive history of previously treated Hepatitis C, but HCV PCR is undetectable off medications for at least 6 months prior to screening, and treating hepatologist or infectious disease specialist believes the subject is cured - subject may be enrolled
- One of the following:
- History of atypical mycobacterial infections (other than MAP). History of active tuberculosis (TB) requiring treatment in the past 3 years. Tuberculosis infection as determined by a positive diagnostic TB test result (defined as a positive or indeterminate (after two independent tests) quantiFERON TB Test Gold test).
- Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or optometrist.
- Any evidence of any other significant hematological, hepatic, renal, cardiac, pulmonary, metabolic, thyroid, neurological or psychiatric disease that might interfere with the subject's ability to safely enter and or complete the study requirements.
- History of malignancy within the past five years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
- Males who do not use barrier contraceptive methods (i.e. condom) with spermicidal foam/gel/cream/suppository or have not had a vasectomy.
- Females who:
- have a positive pregnancy test
- are lactating
- Refusal to sign the study informed consent form.
- Inability to adequately communicate with the investigator or their respective designee and/or comply with the requirements of the entire study.
- History of drug or alcohol abuse within the past 3 years.
- Participation in any experimental drug protocol within 12 weeks of date of screening.
- Cardiac pacemaker or any other type of metal implant or any other contraindication for MRI (including known allergy to gadolinium).
- QTc greater than 440ms, bundle branch block, or major ST or T wave abnormalities that make the assessment of the QT impossible.
- History of unstable cardiac syndromes including unstable angina, coronary artery bypass graft, myocardial infarction or coronary stenting within 2 months of screening; NYHA Class 3-4 CHF; history of ventricular tachycardia, ventricular fibrillation, personal or family history of sudden death, Long QT Syndrome, or Torsade de Pointes; HR<50BPM; having taken any Class 1 or Class 3 antiarrhythmic medications or medicines known to prolong the QT interval or be associated with Torsade de Pointes.
- Treatment with medical cannabis in the 4 weeks prior to screening.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
RedHill MS Clinical Trial Site 002
Tel Aviv
RedHill MS Clinical Trials Site 001
Zefat (Safed)
About this study
Official title: A Phase IIa Proof of Concept Study to Assess the Efficacy and Safety of Fixed Dose Combination RHB-104 as Add-On Therapy to Interferon Beta-1a in Patients Treated for Relapsing Remitting Multiple Sclerosis
The investigators hypothesize that Mycobacterium avium paratuberculosis positive Relapsing Remitting MS subjects will have a greater response to Interferon beta-1a therapy plus RHB-104 than from Interferon beta-1a alone.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- RHB-104
- Keywords
- Relapsing Remitting Multiple Sclerosis, MAP, antibiotic, Interferon beta 1-a, MS, MRI, EDSS, relapse rate
- 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.
RHB-104Drug
95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
| Study group | Role | What they receive |
|---|---|---|
| RHB-104 | Experimental | 5 RHB-104 capsules administered orally BID Receives: Drug: RHB-104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined Unique Active lesions
Measured: Baseline through Wk 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2012 (estimated)
- Study startJun 2013
- Primary completionDec 2015
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing Remitting Multiple SclerosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- RedHill Biopharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ira N Kalfus, MD, Study director, RedHill BiopharmaRadi Shahien, MD, Principal investigator, Ziv Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01717664
- Sponsor's protocol ID
- RHB-104-02
- Acronym
- CEASE-MS
- Status last verified
- Jul 2016
- First submitted
- 24 Oct 2012
- Last updated
- 28 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Proof of Concept Study to Assess the Efficacy and Safety of Fixed Dose Combination RHB-104 as Add-On Therapy to Interferon Beta-1a in Patients Treated for Relapsing Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01717664
- Acronym / sponsor ID
- CEASE-MS / RHB-104-02
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- Relapsing Remitting Multiple Sclerosis, MAP, antibiotic, Interferon beta 1-a, MS, MRI, EDSS, relapse rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- RedHill Biopharma LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 30 Oct 2012 (estimated)
- 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.
The investigators hypothesize that Mycobacterium avium paratuberculosis positive Relapsing Remitting MS subjects will have a greater response to Interferon beta-1a therapy plus RHB-104 than from Interferon beta-1a alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RHB-104 | Experimental | Drug: RHB-1045 RHB-104 capsules administered orally BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males and females aged ≥18 years
- Signed fully informed consent provided as per this protocol and willing to comply with the required scheduled assessments of the protocol.
- Diagnosis of relapsing-remitting multiple sclerosis (McDonald Criteria (2010)) with dissemination in time and space.
- Currently treated with a stable dose of Rebif®, or Avonex® for a minimum of 3 months duration prior to the screening visit.
- Active MS with history of at least one flare within the past 12 months or two flares in the past 24 months prior to screening.
Key exclusion criteria (37 listed)
- Treatment with any other biological therapies including but not limited to Interferon beta-1b, natalizumab, anti-TNF biologic agents, or other agents intended to reduce TNF ≤ 8 weeks prior to screening or within 5 half-lives of agent prior to screening, whichever is longer.
- Previous treatment with rifabutin and/or clofazimine.
- Previous treatment with amiodarone.
- Oral or parenteral antibiotics in the 4 weeks prior to screening. (Topical antibiotics are permitted.)
- Use of Methylprednisolone sodium succinate, prednisone, or any other corticosteroid during the 30 days prior to screening.
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 |
|---|---|---|
| RHB-10495 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine | Drug | RHB-104 |
Primary outcome
Combined Unique Active lesions
Time frame: Baseline through Wk 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2016.
Related trials for Relapsing Remitting Multiple Sclerosis
Active, not recruiting
Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)
PARKINSON DISEASE (Disorder), Multiple Sclerosis (MS) - Relapsing-remitting
Recruiting
Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study
Multiple Sclerosis (MS) - Relapsing-remitting, Upper Extremity Dysfunction
Not yet recruiting
Treatment of Memory Retrieval Impairments in MS With HDtDCS to the LIFG in a Placebo Controlled Trial
Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis (RRMS)
Recruiting
Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity
Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
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.
Ira N Kalfus, MD study director
RedHill Biopharma
Radi Shahien, MD principal investigator
Ziv Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RHB-104 in people with Relapsing Remitting Multiple Sclerosis, run by RedHill Biopharma Limited at 2 sites in Israel.
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 8 inclusion and 37 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: finished, as of the sponsor's last update on 28 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Combined Unique Active lesions (time frame: Baseline through Wk 24). 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 28 Jul 2016.