Clinical trial NCT03009396: Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease
Official title: An Open Label Study to Assess the Efficacy and Safety of Fixed-Dose Combination RHB-104 in Subjects With Active Crohn's Disease Despite 26 Weeks of Participation in the MAP US RHB-104-01 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Crohn's Disease,
moderate to severe
remission
Mycobacterium avium paratuberculosis
antibiotic
Lead sponsor: RedHill Biopharma Limited
Sponsor class: INDUSTRY
First posted: 2017-01-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Active
Primary purpose: TREATMENT

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

Detailed description: An Open Label Phase III Study to Assess the Efficacy and Safety of Fixed-Dose Combination RHB-104 in Subjects with Active Crohn's Disease Despite 26 Weeks of Participation in the MAP US RHB-104-01 Study.

Eligibility criteria: Inclusion Criteria:

* 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.

OR

* 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.

Exclusion Criteria:

1. Positive stool results for C. difficile.
2. Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or optometrist.
3. 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/
4. 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.
5. 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.
6. Females who have a positive pregnancy test or are lactating.
7. Refusal to sign the study informed consent form.
8. Inability to be able to adequately communicate with the investigator or their respective designee and/or comply with the requirements of the entire study.
9. 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.
10. 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.

Primary outcomes:
measure: Number of Patients in Remission at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Response at Week 16
timeFrame: Week 16
measure: The Number of Weeks for Patients to Achieve Remission
timeFrame: Baseline through week 52
measure: Number of Weeks the Patients Are in Remission
timeFrame: Baseline through week 52
measure: Number of Weeks to Achieve Response
timeFrame: Baseline through week 52
measure: Number of Weeks the Patients Are in Response.
timeFrame: Baseline through week 52
measure: Durable Remission Week 16 Through Week 52
timeFrame: Week 16 through week 52
Other outcomes:
measure: Increase in Milliseconds (ms) QT Wave
timeFrame: week 52
Locations:
city: San Carlos
country: United States
facility: Digestive Care Associates, Inc., 1000 Laurel Street
state: California
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300
state: Georgia
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, 720 SW Lane St.
state: Kansas
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research, 5550 Friendship Blvd.
state: Maryland
city: Brockton
country: United States
facility: Commonwealth Clinical Studies, 189 Quincy St.
state: Massachusetts
city: Chattanooga
country: United States
facility: ClinSearch 6035 Shallowford Road Suite 109
state: Tennessee
city: Victoria
country: Canada
facility: Discovery Clinical Services Ltd., 601 A Discovery St.
state: British Columbia
city: Hradec Kralove
country: Czechia
facility: Gastroenterologie s.r.o. Manesova 646
city: Hradec Králové
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o., Hradecka poliklinika III Trida Edvarda Benese 1549/34
city: Afula
country: Israel
facility: Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard
city: Jerusalem
country: Israel
facility: Gastroenterology Institute, Division of Medicine, Hadassah - Hebrew University Medical Center POB 12000
city: Kfar-Saba
country: Israel
facility: Meir Medial Center, 59 Tchemacovsky St.
city: Christchurch
country: New Zealand
facility: Christchurch Hospital, 2 Riccarton Rd.
state: Canterbury
city: Hamilton
country: New Zealand
facility: Waikato Hospital, Department of Gastroenterology, Level B1, Menzies Building, Pembroke Street
state: Waikato
city: Białystok
country: Poland
facility: NZOZ Specjalistyczne Centrum Gastrologii GASTROMED, Wiejska 81
city: Gdansk
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW W Gdańsku Oddział Gastroenterologiczny, Ul. Kartuska 4/6
city: Kraków
country: Poland
facility: UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA. Specjalistyczne Centrum Medyczne Sp. z o.o., Kluczborska 15
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18
city: Szczecin
country: Poland
facility: EuroMedis sp. z.o.o., Al. Powstancow Wielkopolskich 33a
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSW w Warszawie. Klinika Chorob Wewnetrznych i Gastroenterologii, Woloska 137,
city: Wroclaw
country: Poland
facility: ARS MEDICA s.c., Powstancow Slaskich 56A/2
city: Belgrade
country: Serbia
facility: Clinical Department of Gastroenterology and Hepatology Clinic for Internal Diseases Clinical Hospital Center Zvezdara Dimitrija Tucovica 161
city: Belgrade
country: Serbia
facility: Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun, Vukova 9
city: Kragujevac
country: Serbia
facility: Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center Kragujevac, Zmaj Jovina 30
Study officials:
affiliation: RedHill Biopharma Limited
name: Ira N Kalfus, MD
role: STUDY_DIRECTOR
affiliation: Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston
name: David Y Graham, MD
role: PRINCIPAL_INVESTIGATOR
References: