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Crohn DiseasePhase 3MAPUS2NCT03009396

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

A Phase 3 study testing RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine) in people with Crohn Disease, run by RedHill Biopharma Limited at 24 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

An open label extension to the RHB-104-01 Study. Read more about this study

Who is it for?
Ages 18 to 76 years
Conditions the study is for
Crohn Disease
What is being tested?
RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
24 sitesin 7 countries
Study dates
18 Mar 2017to 19 Aug 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 76 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

24 sites in 7 countries.

24 sites in 7 countries

Poland7 sites
  • NZOZ Specjalistyczne Centrum Gastrologii GASTROMED, Wiejska 81

    Bialystok, 15-351

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

    Gdansk, 80-104

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

    Krakow, 31-271

  • Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18

    Olsztyn, 10-561

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

    Szczecin, 70-111

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

    Warsaw, 02-507

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

    Wroclaw, 53-333

Other trials in Poland

United States6 sites
  • Commonwealth Clinical Studies, 189 Quincy St.

    Brockton, Massachusetts, 02302-2926

  • ClinSearch 6035 Shallowford Road Suite 109

    Chattanooga, Tennessee, 37421

  • Chevy Chase Clinical Research, 5550 Friendship Blvd.

    Chevy Chase, Maryland, 20815

  • Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300

    Marietta, Georgia, 30060

  • Digestive Care Associates, Inc., 1000 Laurel Street

    San Carlos, California, 94070

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

    Topeka, Kansas, 66606

Other trials in United States

Israel3 sites
  • Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard

    Afula, 1834111

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

    Jerusalem, 91120

  • Meir Medial Center, 59 Tchemacovsky St.

    Kfar Saba, 44281

Other trials in Israel

Serbia3 sites
  • Clinical Department of Gastroenterology and Hepatology Clinic for Internal Diseases Clinical Hospital Center Zvezdara Dimitrija Tucovica 161

    Belgrade, 11000

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

    Belgrade, 11080

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

    Kragujevac, 34000

Other trials in Serbia

Czechia2 sites
  • Gastroenterologie s.r.o. Manesova 646

    Hradec Králové, 500 02

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

    Hradec Králové, 500 12

Other trials in Czechia

New Zealand2 sites
  • Christchurch Hospital, 2 Riccarton Rd.

    Christchurch, Canterbury, 80011

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

    Hamilton, Waikato Region, 3240

Other trials in New Zealand

Canada1 site
  • Discovery Clinical Services Ltd., 601 A Discovery St.

    Victoria, British Columbia, V8T 5G4

Other trials in Canada

About this study

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

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

Read the 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.

Conditions
Crohn Disease
Being tested
RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)
Keywords
Crohn's Disease,, moderate to severe, remission, Mycobacterium avium paratuberculosis, antibiotic
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called RHB-104

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

Study groups in NCT03009396
Study groupRoleWhat they receive
RHB-104 - patients on ACTIVE therapy in RHB-104-01 studyExperimentalSubjects 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
Receives: 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 studyExperimentalSubjects 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.
Receives: Drug: RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 16

Secondary outcomes (6)
  1. Response at Week 16

    Reduction of the total Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points Lower CDAI scores indicate a better outcome.

    Measured: Week 16

  2. The Number of Weeks for Patients to Achieve Remission

    [Date of first observed remission (CDAI less than 150) - date of first dose, or date of randomization if not dosed, plus 1] / 7 days. Subject who never experience remission during the study are censored at the time of their last CDAI assessment.

    Measured: Baseline through week 52

  3. Number of Weeks the Patients Are in Remission

    Duration of remission is defined as the number of weeks the subject is in remission (CDAI score < 150). It is calculated as the first date following remission at which CDAI is ≥150 minus the date of first remission, plus 1 day, divided by 7. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.

    Measured: Baseline through week 52

  4. Number of Weeks to Achieve Response

    [Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.

    Measured: Baseline through week 52

  5. Number of Weeks the Patients Are in Response.

    Duration of response is defined as the number of weeks the subject is in a state of response (a reduction from baseline of ≥ 100 in CDAI score). It is calculated as the first date following response at which the reduction from baseline in CDAI is <100 minus the date of first response, plus 1 day, divided by 7. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.

    Measured: Baseline through week 52

  6. Durable Remission Week 16 Through Week 52

    When a subject is in remission with a maximum CDAI score of 149 at every visit from week 16 through and including week 52.

    Measured: Week 16 through week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2017 (estimated)
  2. Study start18 Mar 2017
  3. Primary completion13 Nov 2018
  4. Study completion19 Aug 2019

Resources

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Active
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03009396
Sponsor's protocol ID
RHB-104-04
Acronym
MAPUS2
Status last verified
Feb 2021
First submitted
26 Dec 2016
Last updated
24 Feb 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine) in people with Crohn Disease, run by RedHill Biopharma Limited at 24 sites in 7 countries.

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 14 inclusion and 11 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 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Poland, United States, Israel, Serbia, Czechia and 2 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Patients in Remission at Week 16 (time frame: Week 16). 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 24 Feb 2021.

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