Study IM011-077 is a Phase 2 randomized, open-label, multicenter clinical study designed to assess the safety and tolerability, efficacy and biomarker response of deucravacitinib 6 mg BID (twice daily) in subjects with moderate to severe Ulcerative…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study will be to assess the safety and
tolerability of long-term use of deucravacitinib in participants with moderate
to severe CD.
This will be measured by collecting the number and proportion of participants
experiencing Adverse Events (AEs), Serious AEs (SAEs), AEs leading to study
discontinuation and AEs of Interest (AEIs).
The number and proportion of participants experiencing abnormalities in the
laboratory testing, ECG and vital sign parameters over time.
Changes from Day 1 for laboratory testing, ECG and vital signs will also be
measured.
Secondary outcome
Secondary objectives of the study are as follows:
• To assess the effect of long-term use of deucravacitinib in participants with
moderate to severe UC and CD
This will be measured by a number of factors including the proportion of
participants with clinical remission, clinical response, endoscopic response,
endoscopic remission, histologic remission, mucosal healing.
• To assess the effect of long-term use of deucravacitinib on health-related
quality of life
This will be measured by a number of factors including the Inflammatory Bowel
Disease (IBD) Questionnaire, Stool Frequency (SF) questionnaire and bowel
urgency response.
• To obtain data regarding the effect of long-term use of deucravacitinib on
healthcare utilisation
This will be measured by the proportion of participants with IBD-related
hospitalisation and IBD-related surgery
• To obtain data regarding the effect of long-term use of deucravacitinib on PK.
This will be measured from plasma sample concentrations of deucravacitinib over
the course of the study
• To obtain data regarding the effect of long-term use of deucravacitinib on
biomarkers.
This will be measured by the change from baseline in faecal calprotectin and
faecal lactoferrin over time, in addition to the change from baseline of
inflammatory biomarkers over time in circulation and tissues
• To assess the impact of SARS-CoV-2 serologic status on participants receiving
deucravacitinib.
This will be measured by checking the levels of SARS-CoV-2 in the blood over
the course of the study.
Background summary
IM011-077 is a multicentre, phase 2, open-label study involving patients with
moderate to severe Ulcerative Colitis (UC) and Crohn's Disease (CD). The study
will assess the long-term safety and efficacy of deucravacitinib (BMS-986165).
Approximately 300 participants are expected to rollover from the parent studies
into Study IM011-077. All participants must have completed 1 of the parent
studies (Studies IM011-023, IM011-024, or Study IM011-127) and must meet all
eligibility criteria.
Approximately 300 participants are expected to rollover from the parent studies
into Study IM011077. All participants must have completed 1 of the parent
studies (Studies IM011023, IM011024, or Study IM011127) and must meet all
eligibility criteria.
Participants will receive deucravacitinib 6 mg twice a day, by mouth, in a
tablet formulation.
UC and CD are chronic inflammatory diseases of the gastrointestinal tract which
have an impact on mortality and quality of life. The management and treatment
of these diseases have placed a huge demand on various healthcare services.
Despite new treatment options which have become available over the last several
years, significant challenges remain. Current treatments are often ineffective,
only inducing are temporary response. In other cases the treatment regimens can
cause toxic side effects. There still remains a significant need for
well-tolerated and effective treatments.
Deucravacitinib is a selective Tyrosine Kinase 2 (TyK2) inhibitor. TyK2 is an
enzyme involved in various signalling pathways found within the cell known as
cytokines: interleukin (IL)-12, IL-23 and Type I interferon (IFN) signalling.
The TyK2 enzyme works by speeding up the transfer of phosphate groups from
high-energy, phosphate-donating molecules to specific proteins. This process is
known as phosphorylation. The phosphorylation of these proteins results in the
downstream activation of specific responses for these signalling pathways.
TyK2 is widely expressed. TYk2-dependent signalling pathways and the chemical
messengers that they modulate are thought to be involved in the onset and
development of various immune-mediated diseases including UC, CD, psoriasis,
psoriatic arthritis and systemic lupus erythematous (SLE).
Data from this study will be analysed to:
(i) Assess the safety and tolerability of long-term sue of deucravacitinib in
participants with moderate to severe UC and CD
(ii) Assess the long-term use of deucravacitinib in participants with moderate
to severe UC and CD
(iii) Assess the effect of long-term use of deucravacitinib on health-related
quality of life.
(iv) Obtain data regarding the effect of long-term use of deucravacitinib on
healthcare utilization.
(v) Obtain data regarding the PK long-term use of deucravacitinib following
long-term use in participants
(vi) Obtain data regarding the effect of long-term use of deucravacitinib on
biomarkers
(vii) To assess the safety impact of SARS-CoV-2 serologic status on
participants receiving deucravacitinib
Study objective
Study IM011-077 is a Phase 2 randomized, open-label, multicenter clinical study
designed to assess the safety and tolerability, efficacy and biomarker response
of deucravacitinib 6 mg BID (twice daily) in subjects with moderate to severe
Ulcerative Colitis and Crohn's Disease.
Study design
Approximately 300 patients will participate in the study. The total number
patients that take part in the Netherlands will depend on the number of
eligible participants that have completed one of the parent studies. There are
3 BMS parent phase 2 deucravacitinib studies - one for participants with
moderate to severe Crohn's Disease (CD) (Study IM011023) and two for
participants with moderate to severe ulcerative colitis (UC) (Studies IM011024
and IM011127).
Participation on the study will last about 6 years. The exact duration will
depend on how well the participant tolerates the study treatment.
The study is divided into three periods:
• Screening
• Treatment: up to 6 years
• Follow-up: 4 weeks (28 days)
During the screening visit the participant will undergo test to confirm whether
they can participate. These tests include a physical examination, ECG,
measurement of weight and vital signs, and collection of blood, urine and stool
samples. An endoscopy with biopsy may also be performed.
When this screening visit occurs less than 14 days from the last visit of the
parent study, only one set of samples will be taken, and the results will be
used in both studies. If this visit occurs greater than or equal to 14 days and
less than or equal to 28 days from the last visit of the parent study, certain
procedures will need to be repeated except the endoscopy with biopsy. When this
visit occurs greater than 28 days from the last visit in the parent study, all
procedures will need to be repeated and the study investigator will inform the
participant if the endoscopy with biopsy needs to be repeated.
All participants will receive deucravacitinib 6 mg daily in the form of a
tablet. The study drug should be taken once in the morning and once in the
evening.
After patients have completed the treatment period or for those who permanently
discontinue the study drug before the end of the treatment period, they will
enter a 4 week post treatment follow-up period.
DMC
A Data Monitoring Committee will provide oversight on the safety of trial
participants within this study. The DMC will regularly review accumulating data
from this study and advise the Sponsor regarding the continuing safety of trial
participants, as well as the continuing validity and scientific merit of the
trial.
Data summaries and listings will be provided to the DMC to assist their safety
assessment of the study, at regularly scheduled meetings and on an ad hoc basis
if needed. The DMC will also be provided with suspected, unexpected serious
adverse reaction (SUSAR) reports relating to deucravacitinib and
recommendations from other DMCs supporting the deucravacitinib clinical
development program.
Regular DMC safety reviews will include all AEs, SAEs, and AEIs. Based on their
review of safety data, the DMC will make recommendations regarding the
appropriateness of continuing the study, with or without study modifications,
or stopping the study. The DMC may request select efficacy data from the
blinded parent studies for benefit-risk assessment and study continuation.
Intervention
Patients who have completed screening procedures (up to 28 days duration) and
meet inclusion/exclusion criteria will be randomized on Day 1 of the treatment
period.
All participants will receive deucravacitinib 6mg twice daily by mouth (PO) in
a tablet formulation, for up to 6 years.
Participants will undergo the same on treatment study evaluation procedures:
assessments of medical history, prior medications, concomitant medications,
tobacco use, baseline Stool Frequency; blood, stool and urine collection for
checking safety, pharmacokinetics, and biomarkers, vital signs monitoring,
endoscopy with biopsies, ECG, additional efficacy assessments, questionnaires
and patient collection of PROs in daily electronic diaries.
Once participants complete the study treatment period, they will begin the last
part of the study, the follow-up period. During this period the investigator
will continue to assess the patients' health. The follow-up period includes 1
visit at the study center. If the investigator thinks it's necessary additional
visits may be necessary to further evaluate the safety or efficacy of the drug.
Study burden and risks
Several sources of research suggest that inhibition of TYK 2 signalling by
deucravacitinib may be beneficial to patients with Ulcerative Colitis (UC) and
Crohn's Disease (CD).
Deucravacitinib has previously been studied in parent studies IM011-023 (for
participants with moderate to severe CD), IM011-024 and IM011-127 (for
participants with moderate to severe UC).
Study IM011-127 was the first study involving patients with moderate to severe
UC. In this placebo controlled study participants received deucravacitinib at
doses 6-12 mg twice daily, for up to 52 weeks. The current study (IM011-077)
has been designed to closely monitor patients' safety throughout, over a longer
period (6 years). Participants enrolling in the study will have had 1 to 2
years of safety monitoring while receiving deucravacitinib. Safety monitoring
will continue at study sites, by the Sponsor, and also by an external,
independent Data Monitoring Committee.
The inclusion/ exclusion criteria, tests and procedures for this study are
aligned with the parent studies. The similarity between the studies will allow
for data from the current study to be analysed alone, and compared with the
data collected in the parent studies. This may also help to determine dose
selection for phase 3 trials of deucravacitinib.
The safety and tolerability of deucravacitinib has been investigated at
multiple doses (including 6mg) in healthy volunteers and patients with
psoriasis in phase 2 studies. The results from these studies indicate and
overall favourable benefit-risk assessment for investigating further treatment
of patients with CD and UC.
Adverse Events of Interest (AEIs) have been defined, based on the mechanism of
action of BMS-986165 (deucravacitinib) and the observed safety profile in the
BMS-986165 clinical trial program. The eligibility and randomization criteria
have been clearly defined to ensure to minimize the risk for AEIs such as
infections or malignancy, which may be associated with immunomodulator use.
(Deucravacitinib is an immunomodulatory Investigational Product and potential
Immunosuppressant). Frequent study visits and safety assessments, with
monitoring of subject safety by investigators, the Sponsor, and the Data
Monitoring Committee are designed to promote the safety of subjects within this
study. Furthermore all participants may remain on permitted background Standard
of Care (SOC) therapy. The protocol provides details on how to manage treatment
failure and increase in Inflammatory bowel disease activity.
Testing will be done to exclude participants with COVID-19 infection prior to
enrollment. Study treatment will be interrupted in the event there is a
positive test for SARS-CoV-2 or clinical suspicion for COVID-19 infection.
Data Monitoring Committee (DMC)
An external, independent DMC will provide oversight on the safety of patients
within this study, The DMC will regularly review accumulating data from this
study, and advise the Sponsor regarding the continuing safety of trial subjects
and those yet to be recruited to the trial, as well as the continuing validity
and scientific merit of the trial.
Data summaries and listings will be provided to the DMC to facilitate their
safety assessment at regularly scheduled meetings and on an ad hoc basis if
needed. The DMC will also be provided with suspected, unexpected serious
adverse reaction (SUSAR) reports relating to deucravacitinib.
Regular DMC safety reviews will include all AEs, SAEs, and AEs of special
interest. Based on their review of safety data, the DMC will make
recommendations regarding the appropriateness of continuing the study, with or
without study modifications, or stopping the study.
Deucravacitinib could provide clinical benefit and improvements in the outcomes
for patients with UC and CD. However, with all experimental drugs and clinical
trials, there are known and unknown risks. Study medication and procedure
related risks are outlined in the patient information sheet in detail to ensure
the patients are fully informed before agreeing to take part in the study.
As part of the trial, patients will be expected to attend multiple clinic
visits where they will undergo physical examinations, vital sign measurements,
endoscopy, biopsy, ECG, blood, stool and urine tests for safety assessment,
pregnancy testing (for females of child bearing potential) and monitoring for
adverse events.
Blood will also be collected at certain visits for research purposes (PK, and
biomarker studies).
Patients will be asked to complete an electronic diary about their stool
frequency, daily throughout the screening and treatment periods. They will also
be required to complete questionnaires about their UC and CD and quality of
life at various points throughout the study.
Patients will be required to take tablets twice daily for up to 6 years, during
the treatment period. The diary and pill bottle will be reviewed by site-staff.
Subjects are required to fast for a minimum of 10 hours before the
randomization visit (Day 1) and the Week 48 (visit 5), as fasting lipid and
glucose samples will be obtained at those times.
Women of child-bearing potential must agree to follow instructions for methods
of contraception for the duration of treatment with the study drug.
Use of tobacco products will be assessed at each study visit.
Study treatment may be taken without regard to meals.
The investigation medicinal products could provide clinical benefit and
improvements in the outcomes for patients with UC & CD. However, with all
experimental drugs and clinical trials, there are known and unknown risks.
Study medication and procedure related risks are outlined in the patient
information sheet in detail to ensure the patients are fully informed before
agreeing to participate.
Orteliuslaan 1000
Urecht 3528 BD
NL
Orteliuslaan 1000
Urecht 3528 BD
NL
Listed location countries
Age
Inclusion criteria
1) Signed Written Informed Consent
a) Participants must be willing to participate in Study IM011077 and must have
the ability to sign the informed consent form.
b) Willing and able to complete all study specific procedures and visits.
2) Type of Participant and Target Disease Characteristics
a) Previously completed OLE treatment in 1 of the parent CD or UC studies;
b) Be in clinical response or clinical remission at Week 104 of Study IM011023
or Study IM011024, or Week 52 of Study IM011127;
• Evidence of clinical response or clinical remission (compared with baseline
in the parent study) as defined by CDAI or modified Mayo score;
AND
• No worsening of endoscopy (by SES-CD or Mayo endoscopic subscore) from the
parent study baseline (as assessed by local read).
3) Age and Reproductive Status
Investigators shall counsel women of childbearing potential (WOCBP)
participants, and male participants who are sexually active with WOCBP, on the
importance of pregnancy prevention and the implications of an unexpected
pregnancy.
• The investigator shall evaluate the effectiveness of the contraceptive method
in relationship to the first dose of study intervention.
• Local laws and regulations may require the use of alternative and/or
additional contraception methods.
a) Female Participants
• Females, age 18 or local age of majority and older at the time of enrollment.
• Women who are not of childbearing potential are exempt from contraceptive
requirements.
• Women participants must have documented proof that they are not of
childbearing potential.
• WOCBP must have a negative highly sensitive urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin)
within 24 hours prior to the start of study treatment.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be
excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy.
• WOCBP must agree to follow instructions for method(s) of contraception as
described below and included in the ICF.
• WOCBP are permitted to use hormonal contraception methods as described.
• A female participant is eligible to participate if she is not pregnant or
breastfeeding and at least one of the following conditions applies:
(1) Is not a WOCBP, OR
(2) Is a WOCBP and using a contraceptive method(s), during the treatment period
(at a minimum until after the last dose of study treatment).
b) Male Participants
• Males, age 18 or local age of majority and older at the time of enrollment.
• Male participants should maintain their usual practice with regard to
contraception (if any); however, no specific contraceptive measures are
required.
Exclusion criteria
Exclusion Criteria
1) Medical Conditions
a) Women who are pregnant or breastfeeding.
2) Gastrointestinal Exclusion Criteria
a) Current colonic adenomas or dysplasia diagnosed at the endoscopy performed
at the end of treatment visit of the parent study or past confirmed colonic
dysplasia in the parent study that has not been eradicated.
A participant with adenomatous polyps may be eligible if the polyps have been
completely removed (documented) and the participant is free of polyps at
enrollment (Day 1).
A participant with mucosal dysplasia may be eligible if the dysplasia has been
completely removed/resected/eradicated (as applicable, documented), and the
participant is free of dysplasia at enrollment (Day 1). This should be
discussed with the BMS Medical Monitor/designee prior to enrollment.
Participants must be current with surveillance for dysplasia and screening for
colorectal cancer (based on local guidelines).
3) Immune and Infectious Disease Exclusion Criteria
a) Known serious infection, defined as any infection requiring hospitalization
or treatment with parenteral (intramuscular [IM] or IV) antimicrobial agents
(eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 30
days of the first dose of study treatment.
Antibiotics used to cover a procedure such as endoscopy would not exclude the
participant. Prophylactic antibiotic use should be discussed with the BMS
Medical Monitor/designee.
Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have
resolved and, based on investigator assessment in consultation with the BMS
Medical Monitor/designee, there are no sequelae that would place the
participant at a higher risk by receiving investigational treatment.
4) Prior/Concomitant Therapy
a) Have received any of the following therapies since the first dose of study
treatment in the parent study or before Day 1 in Study IM011077:
i) Treatment with an immunomodulatory or biologic agent for the treatment of
IBD.
ii) Treatment with an investigational agent other than deucravacitinib.
iii) Treatment with D-penicillamine, leflunomide, thalidomide, S1P
inhibitors (eg, ozanimod, fingolimod, and etrasimod), or JAK inhibitors (eg,
tofacitinib, upadacitinib, and filgotinib).
b) Are currently receiving or require initiation of any of the following
therapies:
i) Treatment with corticosteroids at a dose that exceeds the prednisone
equivalent of
7.5 mg/day for adrenal insufficiency.
ii) Treatment with immunomodulatory agents (eg, azathioprine, 6-mercaptopurine,
or methotrexate).
c) Treatment with a live vaccine or live attenuated vaccine within 90 days
prior to Visit 1 of this trial.
d) Prophylactic antibiotic use should be discussed with the BMS Medical
Monitor/designee.
5) Physical and Laboratory Test Findings
a) Evidence of active or latent tuberculosis
Participants diagnosed with latent TB infection (LTBI) in the parent study are
eligible to continue in this study if (1) there are no current signs or
symptoms of active TB, (2) the participant has received adequate documented
treatment for LTBI within 5 years of screening in the parent study.
b) Evidence of active hepatitis B virus (HBV) infection as defined.
Participants who were required to have HBV deoxyribonucleic acid
(DNA) tested every 3 months in the parent study will continue to be tested
every 3 months throughout this study.
c) Clinically significant abnormalities in laboratory testing at the second to
last visit in the parent study or most current result available prior to Day 1
including (but not limited to):
i) Hematology:
(1) Hemoglobin level < 8.5 g/dL
(2) White blood cell (WBC) count < 3.0 × 109/L (< 3000/mm3)
(3) Lymphocyte count < 0.75 × 109/L (< 750/mm3)
(4) Neutrophil count < 1.0 × 109/L (< 1000/mm3) (5) Platelet count < 100 ×
109/L (< 100,000/mm3)
ii) Renal Function:
(1) Serum creatinine > 2 × upper limit of normal (ULN) or renal impairment
based on an estimated glomerular filtration rate < 45 mL/min/1.73 m2
(calculated using the Modification of Diet in Renal Disease equation)
iii) Liver-related Blood Tests and Liver Function:
(1) Serum alanine aminotransferase (ALT) > 2 × ULN
(2) Serum aspartate aminotransferase (AST) > 2 × ULN
(3) Serum total bilirubin > 1.5 × ULN
Participants with total bilirubin > 1.5 × ULN who have a confirmed diagnosis of
Gilbert*s syndrome are not excluded from this study but must be discussed with
the BMS Medical Monitor/designee.
(4) Alkaline phosphatase (ALP) > 1.5 × ULN
d) Any other findings on physical examination, vital signs, or clinical
laboratory testing that, in the opinion of the investigator, may place the
participant at an unacceptable risk for participation in this study.
Allergies and Adverse Drug Reaction
e) History of any significant drug allergy (eg, anaphylaxis) or significant
adverse drug reaction (eg, hepatotoxicity).
6) Other Exclusion Criteria
a) Participants with cancer screening or surveillance that is suspicious for
malignancy, or where the possibility of malignancy cannot be reasonably
excluded after additional clinical, laboratory, or other diagnostic
evaluations. Participants with non-melanoma skin cancer are not excluded.
b) Class III or IV congestive heart failure, as classified by the New York
Heart Association (NYHA) Functional Classification or any recent onset of heart
failure resulting in NYHA Class III/IV symptoms.
c) Acute coronary syndrome (eg, myocardial infarction, unstable angina
pectoris) and/or any history of significant cerebrovascular disease (eg,
stroke, cerebral hemorrhage, transient ischemic attack) within 24 weeks before
enrollment.
d) Known history of hereditary galactose intolerance, total lactase deficiency,
or glucose- galactose malabsorption.
e) Prisoners or participants who are involuntarily incarcerated. (Note: Under
certain specific circumstances and only in countries where local regulations
permit, a person who has been imprisoned may be included or permitted to
continue as a participant. Strict conditions apply, and Bristol-Myers Squibb
approval is required.
Eligibility criteria for this study have been carefully considered to ensure
the safety of the study participants and that the results of the study can be
used. It is imperative that participants fully meet all eligibility criteria.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-004461-40-NL |
| ClinicalTrials.gov | NCT04877990 |
| CCMO | NL81621.056.22 |