Proof of Concept Study of RHB-104 as Add-On Therapy to Interferon Beta-1a in Relapsing Remitting Multiple Sclerosis (RRMS) (CEASE-MS)
Verified February 2014 by RedHill Biopharma Limited
Information provided by (Responsible Party):
RedHill Biopharma Limited
First received: October 24, 2012
Last updated: February 20, 2014
Last verified: February 2014
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.
Relapsing Remitting Multiple Sclerosis
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Combined Unique Active lesions [ Time Frame: Baseline through Wk 24 ] [ Designated as safety issue: No ]
Other Outcome Measures:
- Combined Unique Active lesions [ Time Frame: Week 24 to Week 48 ] [ Designated as safety issue: No ]
- Change in cytokine panel [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
- Change in cytokine panel [ Time Frame: Week 24 to Week 48 ] [ Designated as safety issue: No ]
- MAP status as established by polymerase chain reaction (PCR) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
- MAP status as established by polymerase chain reaction (PCR) [ Time Frame: Week 24 to Week 48 ] [ Designated as safety issue: No ]
- Relapses [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
- Relapses [ Time Frame: Week 24 to Week 48 ] [ Designated as safety issue: No ]
- Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
- Expanded Disability Status Scale (EDSS) [ Time Frame: Week 24 to Week 48 ] [ Designated as safety issue: No ]
- Number of participants with adverse events [ Time Frame: Baseline through Week 24 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2014 (Final data collection date for primary outcome measure)
5 RHB-104 capsules administered orally BID
95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 ≥ 3.5x109.
- Treatment with any other biological therapies including but not limited to Interferon beta-1b, natalizumab, anti-tumor necrosis factor (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.
- 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 30 days before screening.
- 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 has the potential to prolong QT interval or cause Torsades de Pointes within 7 days of screening, including: Cisapride, pimozide,astemizole, terfenadine, ergotamine, dihydroergotamine, quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilde, dofetilide and dronedarone.
- Treatment with any medication that is a CYP3A4 substrate, including: colchicine, simvastatin, lovastatin, atorvastatin, verapamil, amlodipine, diltiazem, sildenafil, tadalafil, vardenafil, fluconazole and midazolam.
- Treatment with any contraindicated medications as listed in the prescriber information for each respective antibiotic found in RHB-104. (See Investigator Brochure (IB))
- Serious adverse reaction or hypersensitivity to the study drug or any medications related to the study drug.
- Clinically significant abnormalities of hematology or biochemistry, including but not limited to, elevations greater than 2 times the upper limit of normal of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase or creatinine clearance less than 60 ml/min at screening.
- Serum potassium, magnesium or calcium outside the normal reference range.
- Positive stool results for C. difficile.
- A positive serology for Hepatitis B, Hepatitis C or HIV at screening.
History of the following diseases:
- Atypical mycobacterial infections (other than MAP)
- Active tuberculosis requiring treatment in the past 3 years
- Positive quantiFERON 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.
- 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 are not post-menopausal for at least the previous 12 months, have not had a hysterectomy or tubal ligation or females of child bearing potential who:
- have a positive pregnancy test
- are lactating
- have not used oral contraceptives for at least three continuous months prior to date of screening
- do not use nonhormonal contraceptive methods such as barrier (i.e. diaphragm, cervical cap, and contraceptive sponge) with spermicidal foam/gel/cream/suppository, or intrauterine device (IUD) unless their partner(s) use barrier contraceptive methods with spermicidal foam/gel/cream/suppository or have had a vasectomy
- 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.
- 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).
- Corrected QT interval (QTc)>440ms, bundle branch block, or major 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; New York Heart Association Class 3-4 congestive heart failure; history of ventricular tachycardia, ventricular fibrillation, personal or family history of sudden death, Long QT Syndrome, or Torsade de Pointes; heart rate <50 beats per minute; taking any Class 1 or Class 3 antiarrhythmic medications or medicines known to prolong the QT interval or be associated with Torsade de Pointes.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01717664
|RedHill MS Clinical Trial Site 002
|Tel Aviv, Israel |
|Contact: Oren Weintraub firstname.lastname@example.org |
|Principal Investigator: Arnon Karni |
|RedHill MS Clinical Trials Site 001
|Zefat (Safed), Israel |
|Contact: Wedad Nachle email@example.com |
|Principal Investigator: Radi Shahien, MD |
RedHill Biopharma Limited
||Ira N Kalfus, MD
||Radi Shahien, MD
||Ziv Medical Center
No publications provided
||RedHill Biopharma Limited
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 24, 2012
||February 20, 2014
||Israel: Ministry of Health
Keywords provided by RedHill Biopharma Limited:
Relapsing Remitting Multiple Sclerosis
Interferon beta 1-a
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 24, 2014
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Immune System Diseases
Interferon beta 1a
Physiological Effects of Drugs