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Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 305)

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ClinicalTrials.gov Identifier: NCT03559517
Recruitment Status : Recruiting
First Posted : June 18, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of SHP647 in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

Condition or disease Intervention/treatment Phase
Crohn's Disease Biological: SHP647 Other: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1032 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 305)
Actual Study Start Date : June 25, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: SHP647 25 mg
Participants will receive 25 mg of SHP647 subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.
Biological: SHP647
Subcutaneous injection of SHP647 will be administered using a prefilled syringe.
Other Name: PF-00547659

Experimental: SHP647 75 mg
Participants will receive 75 mg of SHP647 subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.
Biological: SHP647
Subcutaneous injection of SHP647 will be administered using a prefilled syringe.
Other Name: PF-00547659

Placebo Comparator: Placebo
Participants will receive placebo matching with SHP647 subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.
Other: Placebo
Subcutaneous injection of placebo matched with SHP647 will be administered using a prefilled syringe.




Primary Outcome Measures :
  1. Number of Participants With Clinical Remission at Week 16 [ Time Frame: Week 16 ]
    Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11 point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

  2. Number of Participants With Endoscopic Response at Week 16 [ Time Frame: Week 16 ]
    Endoscopic response as measured as a decrease from baseline in simple endoscopic score for Crohn's disease (SES-CD) (ranging from 0 to 56, with higher values indicating more severe disease). Number of participants with endoscopic response will be reported.


Secondary Outcome Measures :
  1. Number of Participants With Clinical Remission as Measured by Crohn's Disease Activity Index (CDAI) at Week 16 [ Time Frame: Week 16 ]
    Clinical remission is defined by Crohn's Disease Activity Index CDAI score. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical remission as measured by CDAI will be reported.

  2. Number of Participants With Enhanced Endoscopic Response at Week 16 [ Time Frame: Week 16 ]
    Enhanced endoscopic response is measured by a decrease from baseline in SES-CD (range from 0 to 56, with higher values indicating more severe disease). Number of participants with enhanced endoscopic response will be reported.

  3. Number of Participants With Clinical Remission by 2-item Patient Reported Outcome (PRO) at Week 16 [ Time Frame: Week 16 ]
    Clinical remission is determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

  4. Number of Participants With Clinical Response at Week 16 [ Time Frame: Week 16 ]
    Clinical response as per 2-item PRO score is to meet at least 1 of the 2 criteria over the 7 most recent days: 1. A decrease in the average daily abdominal pain based on 11-point NRS ranging 0 (No pain) to 10 (Worst imaginable pain), with stool frequency of type 6/7 (very soft/liquid stools) either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission, that is based on the average daily stool frequency of type 6/7 as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]). 2. A decrease from baseline in the average daily stool frequency of type 6/7 as per the BSFS, with the average daily worst abdominal pain either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission (based on average daily abdominal pain using a 11-point NRS). Number of participants with clinical response will be reported.

  5. Number of Participants With Clinical Remission and Endoscopic Response at Week 16 [ Time Frame: Week 16 ]
    Number of participants with both clinical remission by 2-item PRO as determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days and endoscopic response, as measured by a decrease in SES-CD (range from 0 to 56, with higher values indicating more severe disease).

  6. Number of Participants With Complete Endoscopic Healing at Week 16 [ Time Frame: Week 16 ]
    Endoscopic healing at Week 16 as measured by SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) will be assessed. Number of participants with complete endoscopic healing will be reported.

  7. Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -100 at Week 16 [ Time Frame: Week 16 ]
    Clinical response as measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -100 at Week 16 will be reported.

  8. Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -70 at Week 16 [ Time Frame: Week 16 ]
    Clinical response as measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -70 at Week 16 will be reported.

  9. Number of Participants With Clinical Remission Over Time [ Time Frame: Baseline up to Week 16 ]
    Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11-point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

  10. Change From Baseline in Individual and Total Sign/Symptom Score Based on Participant Daily e-Diary Entries at Week 16 [ Time Frame: Baseline, Week 16 ]
    Patient-reported CD clinical signs and symptom data will be collected using a daily e-diary. Participants record abdominal pain severity (numeric rating scale [NRS]), very soft stool/liquid stool frequency (as shown by BSFS [ranging from type 1 {separate hard lumps-like stools} to type 7 {entirely liquid stools}] type 6/7), total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity (none to severe), vomiting frequency, incontinence frequency, abdominal pain used in CDAI and general wellbeing (generally well to terrible).

  11. Number of Participants With Endoscopic Healing at Week 16 [ Time Frame: Week 16 ]
    Endoscopic healing at Week 16 measured as SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) individual variables (Size of Ulcers, Ulcerated surface, Affected surface and Presence of Narrowing) will be assessed as well. Number of participants with endoscopic healing will be reported.

  12. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score [ Time Frame: Baseline, Week 8, Week 12, up to Week 16, or early termination ]
    The IBDQ consists of 32 items grouped into 4 domains scored as bowel (10 to 70), systemic (5 to 35), emotional (12 to 84), and social function (5 to 35). The total score ranges from 32 to 224. For each domain and the total score, a higher score indicates better health-related quality of life

  13. Change From Baseline in Short Form (SF)-36 at Week 16 [ Time Frame: Baseline, Week 16 ]
    The Short form-36 health survey is used to assess HRQL. It consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role- emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

  14. Incidence of Hospitalizations and Total Inpatient Days [ Time Frame: Baseline up to Week 32 ]
    Incidence of all cause hospitalizations and total inpatient days.

  15. Incidence of Crohn's Disease (CD)-related and Other Surgeries [ Time Frame: Baseline up to Week 32 ]
    Incidence of Crohn's disease-related surgeries and other surgical procedures.



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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participants must be between greater than or equal to (>=) 16 and less than or equal to (<=) 80 years of age; participants less than (<) 18 years of age must weigh >=40 kg and must have body mass index >=16.5 kg/m^2.
  • Participants must have active moderate to severe ileal, ileocolic, or colonic CD at baseline as defined by CDAI, presence of ulcerations that are characteristic to CD as determined by a colonoscopy and as defined by the SES-CD score and assessed by the average worst daily abdominal pain and/or average daily stool frequency.
  • Participants must have a documented diagnosis (endoscopic with histology) of CD for >=3 months before screening.
  • Participants must be willing and able to undergo a colonoscopy during screening after all other inclusion criteria have been met.
  • Participants must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as sulfasalazine or mesalamine (5-aminosalicylic acid [5-ASA]), glucocorticoids, or immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) or anti-tumor necrosis factor (anti-TNF). Participants who have had an inadequate response to sulfasalazine or mesalamine should have also failed at least 1 other conventional treatment such as glucocorticoids.
  • Participants receiving any treatment(s) for CD are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
  • Participants are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential.

Key Exclusion Criteria:

  • Participants with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of ulcerative colitis.
  • Participants with colonic dysplasia or neoplasia.
  • Participants with past medical history or presence of toxic megacolon.
  • Participants with presence of enterovesical or enterovaginal fistulae.
  • Participants with current symptomatic diverticulitis or diverticulosis.
  • Participants with obstructive colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period.
  • Participants with past medical history of multiple small bowel resections resulting in clinically significant short bowel syndrome.
  • Participants requiring total parenteral nutrition.
  • Participants with past medical history of bowel surgery resulting in an existing or current stoma.
  • Participants have had prior treatment with SHP647 (formerly PF-00547659).
  • Participants with active enteric infections, Clostridium difficile infection or pseudomembranous colitis, evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that could predispose the participants to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before baseline.
  • Participants with abnormal chest x-ray or other imaging findings at screening, such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy.
  • Participants with evidence of active or latent infection with Mycobacterium tuberculosis (TB) who have not completed a generally accepted full course of treatment before baseline are excluded. All other participants must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon-gamma release assay (IGRA) performed.
  • Participants with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening.
  • Participants with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
  • Participants with a significant concurrent medical condition at the time of screening or baseline, including, but not limited to, the following:

    1. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, GI [except disease under study], endocrine, cardiovascular, pulmonary, immunologic [eg, Felty's syndrome], or local active infection/infectious illness) that, in the investigator's judgment will substantially increase the risk to the participant if he or she participates in the study.
    2. Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
    3. Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.
    4. History of significant cerebrovascular disease within 24 weeks before screening.
  • Participants who have had significant trauma or major surgery within 4 weeks before screening, or with any major elective surgery scheduled to occur during the study.
  • Participants with evidence of or suspected liver disease, liver injury due to methotrexate or primary sclerosing cholangitis.
  • Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).
  • Participants with positive hepatitis C antibody (HCVAb) with confirmation by HCV-ribonucleic acid (RNA) polymerase chain reaction (PCR) reflex testing.
  • Participants with any of the following abnormalities in hematology and/or serum chemistry profiles during screening.

    1. Alanine aminotransferase and aspartate aminotransferase levels >=2.5 times the upper limit of normal (ULN)
    2. Total bilirubin level >=1.5 times the ULN (except where attributed to elevation in unconjugated bilirubin in participants with documented diagnosis of Gilbert's syndrome)
    3. Hemoglobin level <=80 grams per liter (g/L) (8.0 gram per deciliter [g/dL])
    4. Platelet count <=100 × 10^9 per liter (/L) (100,000 cells per cubic millimeter [cells/mm^3]) or >=1000 × 10^9/L (1,000,000 cells/mm^3)
    5. White blood cell count <=3.5 × 10^9/L (3500 cells/mm^3)
    6. Absolute neutrophil count <2 × 10^9/L (2000 cells/mm3)
    7. Serum creatinine level >1.5 times the ULN or estimated glomerular filtration rate <30 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) based on the abbreviated Modification of Diet in Renal Disease Study Equation.
  • Participants with a known infection with human immunodeficiency virus, as documented in their medical history.
  • Participants who have, or who have a history of (within 2 years before screening), serious psychiatric disease, alcohol dependency, or substance/drug abuse.
  • Participants using marijuana (cannabis) or related products for recreational purposes, who have a known dependency per the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (including urine drug screen and medical history).
  • Participants with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
  • Female participants who are planning to become pregnant during the study period.
  • Male participants who are planning to donate sperm and do not agree not to do so for the duration of the study and through 16 weeks after last dose of investigational product.

NOTE: The above Inclusion/Exclusion criteria are NOT exhaustive and other Inclusion/ Exclusion criteria as defined in the protocol may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03559517


Contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
United States, California
Om Research LLC Recruiting
Lancaster, California, United States, 93534
Contact: Jatinder Pruthi    310-684-2494    jpruthi@synergistresearch.com   
Principal Investigator: Jatinder Pruthi, MD         
United States, Indiana
Laporte County Institute For Clinical Research Recruiting
Michigan City, Indiana, United States, 46360
Contact: Minesh Patel    219-879-0333    minbeni1@yahoo.com   
Principal Investigator: Minesh Patel, MD         
United States, Louisiana
Clinical Trials of SWLA LLC Recruiting
Lake Charles, Louisiana, United States, 70601
Contact: Ricardo McCall    337-493-5310    rmccall@insearchgroup.net   
Principal Investigator: Ricardo McCall, MD         
United States, Ohio
Consultants For Clinical Research Inc Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Pradeep Bekal    513-872-4549    pbekal@aol.com   
Principal Investigator: Pradeep Bekal, MD         
United States, Tennessee
Gastro One Recruiting
Germantown, Tennessee, United States, 38138
Contact: Ziad Younes    901-820-0090    zyounes@gastro1.com   
Principal Investigator: Ziad Younes, MD         
Australia, Victoria
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Miles Sparrow    +61398950369    m.sparrow@alfred.org.au   
Principal Investigator: Miles Sparrow, MBBS, MD         
St Vincents Hospital Melbourne Recruiting
Melbourne, Victoria, Australia, 3065
Contact: Nik Ding    +61392312211    nik.ding@svha.org.au   
Principal Investigator: Nik Ding, MD         
Sponsors and Collaborators
Shire
Investigators
Study Director: Study Director Shire

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03559517     History of Changes
Other Study ID Numbers: SHP647-305
First Posted: June 18, 2018    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases