Proof of Concept Study of RHB-104 as Add-On Therapy to Interferon Beta-1a in Relapsing Remitting Multiple Sclerosis (RRMS)

NCT01717664 | Completed Phase 2

• 1 other identifier: RHB-104-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Relapsing Remitting Multiple Sclerosis; MAP; antibiotic; Interferon beta 1-a; MS; MRI; EDSS; relapse rate

Outcome Measures

Primary Outcomes (1)

• Combined Unique Active lesions

  Baseline through Wk 24

Other Outcomes (16)

• Combined Unique Active lesions

  Week 24 to Week 48

• Change in cytokine panel

  Baseline to Week 24

• Change in cytokine panel

  Week 24 to Week 48

Study Arms (1)

RHB-104

EXPERIMENTAL

5 RHB-104 capsules administered orally BID

Drug: RHB-104

Interventions

RHB-104 DRUG

95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine

RHB-104

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (2)

RedHill MS Clinical Trial Site 002

Tel Aviv, Israel

Location

RedHill MS Clinical Trials Site 001

Zefat (Safed), Israel

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

• Ira N Kalfus, MD

  RedHill Biopharma

  STUDY DIRECTOR

• Radi Shahien, MD

  Ziv Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: October 30, 2012
• Study Start: June 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: July 1, 2016
• Last Updated: July 28, 2016

Record last verified: 2016-07

Locations

IL (2)