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Trial details
A study on the Efficacy and Safety of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Crohn’s Disease (CARMEN CD 307)
Current status:
Approved
|
Date registered:
07/01/2020
|
Date last updated:
07/01/2020
Trial version(s)
Current: 11/07/2019
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2019090265
Protocol number
SHP647-307
MOH registration number
3009243/23423
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
12/12/2019
Primary sponsor
Shire Human Genetic Therapies, Inc. ("Shire")
Primary sponsor: Country of origin
USA
Public title
A study on the Efficacy and Safety of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Crohn’s Disease (CARMEN CD 307)
Acronym
CARMEN CD 307
Scientific title
A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Crohn’s Disease (CARMEN CD 307)
Acronym
CARMEN CD 307
Brief summary of the study: English
This study is designed to evaluate the efficacy of SHP647 as maintenance therapy in subjects with moderate to severe CD who fulfilled the efficacy entry criteria of this study including the clinical and/or endoscopic response criteria defined in induction study SHP647-306.
Brief summary of the study: Arabic
تم تصميم هذه الدراسة لتقييم فعالية دواء الدراسة كعلاج الصيانة لدى الأشخاص الذين يعانون من مرض كرون المعتدل إلى الشديد والذين استوفوا معايير دخول فعالية هذه الدراسة بما في ذلك معايير الاستجابة SHP647-306 السريرية و / أو بالمنظار المحددة في الدراسة الحثية .
Health conditions/problem studied: Specify
Moderate to Severe Crohn Disease
Interventions: Specify
This study consists of a 52-week, double-blind treatment period, followed by a 16-week safety follow-up period for subjects who either discontinue treatment early or complete the treatment period and do not enter the long-term safety extension (LTS) study (SHP647-304). Eligible subjects who received active treatment in the induction study and fulfilled the efficacy entry criteria of this study, including achieving endoscopic and/or clinical response, will be randomized as follows: subjects who received 25 mg SHP647 in the induction study will be randomized (1:1) to receive either 25 mg SHP647 or placebo, and subjects who received 75 mg SHP647 in the induction study will be randomized (1:1) to receive either 75 mg SHP647 or placebo. Eligible subjects who received placebo in the induction study and fulfilled the efficacy entry criteria of this study, including achieving endoscopic and/or clinical response, will be randomized in a 2:2:1 ratio to receive 1 of 3 treatments (25 mg SHP647, 75 mg SHP647, or placebo, respectively) during this maintenance study. Subjects enrolled in this study (SHP647-307) will receive double-blind maintenance treatment in the form of SC injections, using a prefilled syringe (PFS), every 4 weeks for 52 weeks. Subjects will undergo efficacy, biomarker, pharmacokinetic (PK), safety, and health outcome assessments. Subjects who complete the double-blind treatment period in this maintenance study may be eligible to enter the LTS study (SHP647-304). Subjects who are withdrawn from the study prior to completing the double-blind treatment period due to fulfilling the criteria for treatment failure also may be eligible to enter the LTS study. The intent of providing rescue treatment in the LTS study rather than in this maintenance study following “treatment failure” is to maintain study integrity. Offering treatment in the LTS study after exiting this maintenance study allows non-responder subjects on placebo, as well as subjects on active study drug, to potentially benefit from a prolonged or different dose of active treatment. Subjects will enter a 16-week safety follow-up period if they withdraw early from the treatment period, are treatment failures and do not choose to enter the LTS study (SHP647-304), or who complete the study and do not wish to enter the LTS study. Treatment failure is defined in Section 4.5.1.
Key inclusion and exclusion criteria: Inclusion criteria
1. Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. 2. Subjects must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. 3. Subjects must have completed the 16-week induction treatment period from study SHP647-306 and met the following criteria at baseline in maintenance Study SHP647-307: a) Meet endoscopic response criteria of a reduction in SES-CD from induction study SHP647-306 baseline by ≥25% at Week 16 of induction study SHP647-306 OR b) Meet at least 1 of the following 4 criteria at baseline in maintenance study SHP647-307, in addition to no worsening of endoscopic score as measured by SES-CD relative to induction study SHP647-306 baseline: i. Achieving clinical remission as determined by meeting the criteria for clinical remission using the 2-item PRO, ie, 2-item PRO subscores of average worst daily abdominal pain ≤3 (based on 11-point numerical rating scale [NRS]) over the 7 most recent days* and average daily stool type frequency ≤2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days* ii. A decrease of at least 100 points in CDAI score (CDAI-100) from induction study SHP647-306 baseline. iii. A decrease of ≥30% and at least 2 points from induction study SHP647-306 baseline in the average daily worst abdominal pain over the 7 most recent days*, with the average daily stool frequency of type 6/7 (very soft stools/liquid stools) either: (i) not worsening from induction study SHP647-306 baseline and/or (ii) meeting the criteria for clinical remission, ie, 2-item PRO subscore of average daily stool frequency ≤2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days* iv. A decrease of ≥30% from induction study SHP647-306 baseline in the average daily stool frequency of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days*, with the average daily worst abdominal pain either: (i) not worsening from induction study SHP647-306 baseline and/or (ii) meeting the criteria for clinical remission, ie, 2-item PRO subscore of average worst daily abdominal pain ≤3 (based on 11-point NRS) over the 7 most recent days* *Note: The 7 days may or may not be contiguous during the 10 days of data collection before colonoscopy preparation, depending on days to be excluded because of missing data. If fewer than 7 days are available, the criterion will be calculated on all available most recent 6 or 5 days. If fewer than 5 days are available, the criterion will be treated as missing. 4. Subjects receiving any treatment(s) for CD described in Section 5.2.1 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
80
Key inclusion and exclusion criteria: Exclusion criteria
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in induction study SHP647-306. 2. Subjects who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in induction study SHP647-306. 3. Subjects who are likely to require surgery for CD during the study period, except minor interventions (eg, seton placement for anal fistulas). 4. Subjects are females who became pregnant during induction study SHP647-306, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue using appropriate contraception methods through the conclusion of study participation (Section 4.4). 5. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm, or female subjects who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product. 6. Subjects who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures. 7. Subjects who have developed obstructive colonic stricture, or enterovesical or enterovaginal fistulae during the induction study SHP647-306. 8. Subjects who have a newly diagnosed malignancy or recurrence of malignancy (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). 9. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal [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 subject if he or she participates in the study. 10. Subjects 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 subject inappropriate for entry into this study. 11. Subjects with known exposure to Mycobacterium tuberculosis since testing at screening in induction study SHP647-306 and who have been advised to require treatment for latent or active disease but who are without a generally accepted course of treatment. 12. Subjects with any of the following abnormalities in hematology and/or serum chemistry profiles during the evaluation of the last visit in the SHP647-306 study. If the results are considered by the investigator to be transient and inconsistent with the subject’s clinical condition, may be repeated once prior to enrolment in Study SHP647-307. Alanine aminotransferase and aspartate aminotransferase levels > ou = 3 × the upper limit of normal (ULN) Total bilirubin level > ou =1.5 × ULN or >2 × ULN if the subject has a known documented history of Gilbert’s syndrome Hemoglobin level < ou = 80 g/L (8.0 g/dL) Platelet count < ou = 100 × 109/L (100,000 cells/mm3) or > ou = 1000 × 109/L (1,000,000 cells/mm3)* White blood cell count < ou = 3.5 × 109/L (3500 cells/mm3) Absolute neutrophil count<2 × 109/L (<2000 cells/mm3) Serum creatinine level >1.5 × ULN or estimated glomerular filtration rate <30 mL/min/1.73 m2 based on the abbreviated Modification of Diet in Renal Disease Study Equation. *Note: If platelet count is <150,000 cells/mm3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified. 13. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are sponsor employees directly involved in the conduct of the study. 14. Subjects who are participating in other investigational studies (other than induction study SHP647-306 or plan to participate in other investigational studies during Study SHP647-307.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Active
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Ontamalimab
Type of IMP
Immunological
Pharmaceutical class
IgG2 Monoclonal antibody
Therapeutic indication
Crohn Disease
Therapeutic benefit
This study is designed to evaluate the efficacy of SHP647 as maintenance therapy in subjects with moderate to severe CD who fulfilled the efficacy entry criteria of this study including the clinical and/or endoscopic response criteria defined in induction study SHP647-306. The design of the maintenance study (SHP647-307) for those who completed active treatment in the induction study SHP647-306 and met entry criteria is one of randomized withdrawal, whereby a subject may be randomized to continue treatment on the same dose of active treatment or switched to placebo. This design allows for the assessment of the total and multidimensional benefits of a new drug, which encompass efficacy, safety, convenience, and other factors like the durability of the effect of the drug. As one of the coprimary objectives of this study is clinical remission, rerandomizing placebo-treated subjects from the induction study SHP647-306 who meet entry criteria for the maintenance study (SHP647-307) allows for the greatest number of subjects to potentially be in clinical remission. Rerandomizing placebo-treated subjects who qualify for the maintenance study allows for the greatest number of subjects to potentially benefit from treatment with active treatment. Additionally, randomized withdrawal of subjects on active treatment and rerandomization of placebo-treated subjects entering the maintenance study allows for a full and separate investigation of the induction of clinical remission and maintenance of clinical remission effects of any potential new treatment for CD, such as SHP647. Rerandomizing placebo-treated subjects allows for further investigation of long-term safety of SHP647.
Biospecimen retention
Samples without DNA
Biospecimen description
Target sample size
4
Actual enrollment target size
Date of first enrollment: Type
Actual
Date of first enrollment: Date
30/03/2020
Date of study closure: Type
Actual
Date of study closure: Date
31/01/2023
Recruitment status
Other
Recruitment status: Specify
Study not initiated yet
Date of completion
26/08/2022
IPD sharing statement plan
No
IPD sharing statement description
Not decided yet
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
No Numbers
No numbers
Sources of Monetary or Material Support
Name
Shire Human Genetic Therapies, Inc. ("Shire")
Secondary Sponsors
Name
None
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT Lebanon s.a.r.l.
Lebanon
01-- 612500 ext2040
Zog_Az@Mctcro. com
CRO
Scientific
Shire Human Genetic Therapies, Inc. US
US
300 Shire Way Lexington Post code MA 02421
United States of America
+1 781 482 0852
chantal.letournea u@shire.com
sponsor "Clinical Trial Information Desk"
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Al Zahraa University Hospital
Dr. Mahmoud Hallal
Gastroenterologist
NA
Hammoud Hospital University Medical Center
Dr. Majed Bahlawan
Gastroenterologist
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hammoud Hospital University Medical Center
15/07/2019
ghada aoun
medical@hammoudhospital.org
+9617721021
Countries of Recruitment
Name
Lebanon
Australia
United States of America
Austria
Belgium
Bulgaria
Croatia
Czech Republic
Estonia
Germany
Hungary
Ireland
Italy
Lithuania
Netherlands
Poland
Portugal
Slovakia
Spain
United Kingdom
Bosnia and Herzegovina
Canada
Colombia
Japan
Mexico
New Zealand
Russian Federation
Republic of Serbia
South Africa
Democratic People Republic of Korea
Ukraine
Health Conditions or Problems Studied
Condition
Code
Keyword
Crohn Disease
Crohn s disease, unspecified (K50.9)
CD
Interventions
Intervention
Description
Keyword
SHP647 25 mg
SHP647 will be administered subcutaneously in a PFS 1ml
subjects who received 25 mg SHP647 in one of the induction studies will be randomized (1:1) to receive either 25 mg SHP647 or placebo
SHP647 75 mg
SHP647 will be administered subcutaneously in a PFS 1ml
subjects who received 75 mg SHP647 in one of the induction studies will be randomized (1:1) to receive either 75 mg SHP647 or placebo.
Placebo
The placebo solution will contain the same sterile aqueous buffered solution as the test product but will not contain SHP647
Subjects who fulfill all eligibility criteria and who received placebo in the induction study will be randomized in a 2:2:1 ratio to receive 1 of 3 treatments (25 mg SHP647, 75 mg SHP647, or placebo, respectively) during this maintenance study.
Primary Outcomes
Name
Time points
Measure
Clinical remission
week 52
Clinical remission, as measured by a decrease below prespecified thresholds in the 2-item PRO (abdominal pain severity and very soft stool/liquid stool frequency [as shown in the BSFS]).
Enhanced endoscopic response
week 52
Enhanced endoscopic response, as measured by a decrease in SES-CD.
Key Secondary Outcomes
Name
Time points
Measure
Clinical Remission defined by CDAI score
week 52
Clinical Remission defined by CDAI score at week 52
Glucocorticoid-free Clinical Remission Based on Patient-reported Clinical Signs and Symptoms (2-item PRO)
Week 52
Glucocorticoid-free Clinical Remission at week 52
Clinical Remission Defined by Average Daily Abdominal Pain ≤1 (Based on the 4-point Scale) and Average Daily Stool Frequency ≤3 of Type 6/7
Week 52
Clinical Remission at week 52
Clinical Remission Among Subjects in Clinical Remission at Baseline of the SHP647-307 Study, Based on Patient-reported Clinical Signs and Symptoms (2-Item PRO)
Week 52
Clinical Remission at week 52
Enhanced Endoscopic Response Among Subjects with Enhanced Endoscopic Response at Baseline of the SHP647-307 Study
Week 52
Enhanced Endoscopic Response at week 52
Clinical Remission as Well as Enhanced Endoscopic Response in the Same Subject
Week 52
Clinical Remission as Well as Enhanced Endoscopic Response at week 52
Complete Endoscopic Healing
week 52
Complete Endoscopic Healing at week 52
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial