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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03009396




Registration number
NCT03009396
Ethics application status
Date submitted
26/12/2016
Date registered
4/01/2017
Date last updated
24/02/2021

Titles & IDs
Public title
Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease
Scientific 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
Secondary ID [1] 0 0
RHB-104-04
Universal Trial Number (UTN)
Trial acronym
MAPUS2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn Disease 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)

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

Experimental: RHB-104 - patients on PLACEBO therapy in RHB-104-01 study - 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.


Treatment: Drugs: RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)
For patients on ACTIVE or PLACEBO in the parent study (RHB-104-01), who were not in remission after 26 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Patients in Remission at Week 16
Timepoint [1] 0 0
Week 16
Secondary outcome [1] 0 0
Response at Week 16
Timepoint [1] 0 0
Week 16
Secondary outcome [2] 0 0
The Number of Weeks for Patients to Achieve Remission
Timepoint [2] 0 0
Baseline through week 52
Secondary outcome [3] 0 0
Number of Weeks the Patients Are in Remission
Timepoint [3] 0 0
Baseline through week 52
Secondary outcome [4] 0 0
Number of Weeks to Achieve Response
Timepoint [4] 0 0
Baseline through week 52
Secondary outcome [5] 0 0
Number of Weeks the Patients Are in Response.
Timepoint [5] 0 0
Baseline through week 52
Secondary outcome [6] 0 0
Durable Remission Week 16 Through Week 52
Timepoint [6] 0 0
Week 16 through week 52

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
76 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/08/2019
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Czechia
State/province [8] 0 0
Hradec Kralove
Country [9] 0 0
Czechia
State/province [9] 0 0
Hradec Králové
Country [10] 0 0
Israel
State/province [10] 0 0
Afula
Country [11] 0 0
Israel
State/province [11] 0 0
Jerusalem
Country [12] 0 0
Israel
State/province [12] 0 0
Kfar-Saba
Country [13] 0 0
New Zealand
State/province [13] 0 0
Canterbury
Country [14] 0 0
New Zealand
State/province [14] 0 0
Waikato
Country [15] 0 0
Poland
State/province [15] 0 0
Bialystok
Country [16] 0 0
Poland
State/province [16] 0 0
Gdansk
Country [17] 0 0
Poland
State/province [17] 0 0
Kraków
Country [18] 0 0
Poland
State/province [18] 0 0
Olsztyn
Country [19] 0 0
Poland
State/province [19] 0 0
Szczecin
Country [20] 0 0
Poland
State/province [20] 0 0
Warsaw
Country [21] 0 0
Poland
State/province [21] 0 0
Wroclaw
Country [22] 0 0
Serbia
State/province [22] 0 0
Belgrade
Country [23] 0 0
Serbia
State/province [23] 0 0
Kragujevac

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
RedHill Biopharma Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
An open label extension to the RHB-104-01 Study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03009396
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ira N Kalfus, MD
Address 0 0
RedHill Biopharma Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries