Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease

NCT03009396 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: RHB-104-04
• Study Type: interventional
• Target: 54
• Locations: 7 countries
• Sites: 24

Brief Summary

An open label extension to the RHB-104-01 Study.

Conditions

Crohn Disease

Keywords

Crohn's Disease,; moderate to severe; remission; Mycobacterium avium paratuberculosis; antibiotic

Outcome Measures

Primary Outcomes (1)

• Number of Patients in Remission at Week 16

  The number of patients who achieved a reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150 points. Lower CDAI scores indicate a better outcome.

  Week 16

Secondary Outcomes (6)

• Response at Week 16

  Week 16

• The Number of Weeks for Patients to Achieve Remission

  Baseline through week 52

• Number of Weeks the Patients Are in Remission

  Baseline through week 52

• Number of Weeks to Achieve Response

  Baseline through week 52

• Number of Weeks the Patients Are in Response.

  Baseline through week 52

Other Outcomes (1)

• Increase in Milliseconds (ms) QT Wave

  week 52

Study Arms (2)

RHB-104 - patients on ACTIVE therapy in RHB-104-01 study

EXPERIMENTAL

Subjects who were on the active therapy arm in the RHB-104-01 clinical study will continue to receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study

Drug: RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)

RHB-104 - patients on PLACEBO therapy in RHB-104-01 study

EXPERIMENTAL

Subjects who were on the active therapy arm in the RHB-104-01 clinical study will receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study. The RHB-104 will be ramped up beginning at 1 capsule twice per day in week 1 increasing to 2 capsules twice per day in week 2, 3 capsules twice per day in week 3, 4 capsules per day in week 4 and achieving 5 capsules per day for the remainder of the study.

Drug: RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)

Interventions

RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine) DRUG

For patients on ACTIVE or PLACEBO in the parent study (RHB-104-01), who were not in remission after 26 weeks

Also known as: RHB-104

RHB-104 - patients on ACTIVE therapy in RHB-104-01 study; RHB-104 - patients on PLACEBO therapy in RHB-104-01 study

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed fully informed consent (ICF) provided as per this protocol.
• Participation in RHB-104-01 for 26 weeks, and a Crohn's Disease Activity Index (CDAI) score of ≥ 150 at Visit Week 26.
• More than 26 weeks, with a CDAI ≥150 at Visit Week 26 and all subsequent visits, and subject is between Week 26 and 52 within 4 weeks (28 days) of site activation (e.g. Subject with CDAI = 249 at week 26 and who is at week 38 at the time of site's activation for RHB-104-04 has a 4-week window to be enrolled in the open label study via the Optional Screening Visit)
• Current treatment with at least one of the following therapies which may be discontinued by the investigator as clinically indicated after 8 weeks of open label RHB-104 treatment:
• Oral 5-acetyl salicylic acid (5-ASA) compounds
• Azathioprine or 6-mercaptopurine (6-MP) or methotrexate
• Infliximab or adalimumab OR Current treatment with corticosteroid therapy which must begin tapering after 4 weeks of treatment with open label RHB-104 (Refer to Appendix 13)
• White blood cell count ≥ 3.5x109 at screening (RHB-104-01 Visit Week 26 visit or Optional Screening visit)
• Subject agrees to use the following effective contraceptive methods
• diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository
• IUD (intrauterine device) /IUS (intrauterine system)
• progestogen injection (Depo-Provera®) throughout the study and for at least 6 weeks after last study drug administration, unless subject or partner of subject is post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation, or has had a vasectomy. Post-menopausal is defined as having experienced 12 consecutive months without menstruation.
• In regions where local regulatory contraceptive requirements differ, the ICF (Informed Consent Form) will reflect local policies.

You may not qualify if:

• Positive stool results for C. difficile.
• Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or optometrist.
• Treatment with any medication that causes QT prolongation or Torsades de Pointes, including but not limited to: amiodarone, amitriptyline, astemizole, cisapride, citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide, dronedarone, ergotamine, ibutilide, ondansetron or other 5-HT3 (5-hydroxytryptamine three) receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolones, ranolazine, risperidone, sotalol, terfenadine and tolterodine. QT prolonging drugs may be referenced at the CredibleMeds® web site: https://crediblemeds.org/index.php/drugsearch/
• Treatment with the following CYP3A4 interactive medications: alfentanyl, alprazolam, amlodipine, anti-retroviral agents, apixaban, aprepitant, aripiprazole, atorvastatin, boceprevir, buspirone, carbamazepine, carvedilol, colchicine, cyclosporine, digoxin, diltiazem, estrogens, felodipine, fluconazole, fluvoxamine, grapefruit juice, haloperidol, ketoconazole, lovastatin, lurasidone, metoprolol, nefazodone, nifedipine, nisoldipine, nitrendipine, propranol, roflumilast, simvastatin, St. John's wort, and voriconazole.
• Any evidence of any newly diagnosed significant hematological, hepatic, renal, cardiac, pulmonary, metabolic, neurological, psychiatric or other disease (e.g. porphyria) that might interfere with subject's ability to safely enter and or complete the study requirements.
• Females who have a positive pregnancy test or are lactating.
• Refusal to sign the study informed consent form.
• Inability to be able to adequately communicate with the investigator or their respective designee and/or comply with the requirements of the entire study.
• Clinically significant abnormalities of hematology or biochemistry 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), Alkaline Phosphatase (ALP) or creatinine clearance less than 60 ml/min at screening via estimated Cockcroft-Gault formula:
• Creatinine Clearance = \[140 - age in years\] \* weight (kg) / 72 \* Serum Creatinine (mg/dl) \[multiply estimated rate by 0.85 for women\], using actual body weight.
• QTcF (shortening of the QT interval in the heart rate) \>450ms in males and QTcF\>460ms in females, bundle branch block, or major ST or T wave abnormalities that make the assessment of the QT impossible.

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (24)

Digestive Care Associates, Inc., 1000 Laurel Street

San Carlos, California, 94070, United States

Location

Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300

Marietta, Georgia, 30060, United States

Location

Cotton-O'Neil Clinical Research Center, 720 SW Lane St.

Topeka, Kansas, 66606, United States

Location

Chevy Chase Clinical Research, 5550 Friendship Blvd.

Chevy Chase, Maryland, 20815, United States

Location

Commonwealth Clinical Studies, 189 Quincy St.

Brockton, Massachusetts, 02302-2926, United States

Location

ClinSearch 6035 Shallowford Road Suite 109

Chattanooga, Tennessee, 37421, United States

Location

Discovery Clinical Services Ltd., 601 A Discovery St.

Victoria, British Columbia, V8T 5G4, Canada

Location

Gastroenterologie s.r.o. Manesova 646

Hradec Králové, 500 02, Czechia

Location

Hepato-Gastroenterologie HK, s.r.o., Hradecka poliklinika III Trida Edvarda Benese 1549/34

Hradec Králové, 500 12, Czechia

Location

Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard

Afula, 1834111, Israel

Location

Gastroenterology Institute, Division of Medicine, Hadassah - Hebrew University Medical Center POB 12000

Jerusalem, 91120, Israel

Location

Meir Medial Center, 59 Tchemacovsky St.

Kfar Saba, 44281, Israel

Location

Christchurch Hospital, 2 Riccarton Rd.

Christchurch, Canterbury, 80011, New Zealand

Location

Waikato Hospital, Department of Gastroenterology, Level B1, Menzies Building, Pembroke Street

Hamilton, Waikato Region, 3240, New Zealand

Location

NZOZ Specjalistyczne Centrum Gastrologii GASTROMED, Wiejska 81

Bialystok, 15-351, Poland

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW W Gdańsku Oddział Gastroenterologiczny, Ul. Kartuska 4/6

Gdansk, 80-104, Poland

Location

UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA. Specjalistyczne Centrum Medyczne Sp. z o.o., Kluczborska 15

Krakow, 31-271, Poland

Location

Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18

Olsztyn, 10-561, Poland

Location

EuroMedis sp. z.o.o., Al. Powstancow Wielkopolskich 33a

Szczecin, 70-111, Poland

Location

Centralny Szpital Kliniczny MSW w Warszawie. Klinika Chorob Wewnetrznych i Gastroenterologii, Woloska 137,

Warsaw, 02-507, Poland

Location

ARS MEDICA s.c., Powstancow Slaskich 56A/2

Wroclaw, 53-333, Poland

Location

Clinical Department of Gastroenterology and Hepatology Clinic for Internal Diseases Clinical Hospital Center Zvezdara Dimitrija Tucovica 161

Belgrade, 11000, Serbia

Location

Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun, Vukova 9

Belgrade, 11080, Serbia

Location

Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center Kragujevac, Zmaj Jovina 30

Kragujevac, 34000, Serbia

Location

Related Links

• RedHill home page

MeSH Terms

Conditions

Crohn Disease

Interventions

Clarithromycin; Rifabutin; Clofazimine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenazines; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Reza Fathi, Sn. VP Research and Development
• Organization: Redhill Biopharma

reza@redhillbio.com

972-(0)3-541-3131

Study Officials

• Ira N Kalfus, MD

  RedHill Biopharma Limited

  STUDY DIRECTOR

• David Y Graham, MD

  Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Active

Study Record Dates

• First Submitted: December 26, 2016
• First Posted: January 4, 2017
• Study Start: March 18, 2017
• Primary Completion: November 13, 2018
• Study Completion: August 19, 2019
• Last Updated: February 24, 2021
• Results First Posted: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); CA (1); SE (3); CZ (2); IL (3); PL (7); US (6)