Crohn Disease
Conditions
Keywords
APOLLO-CD, APOLLO, Crohn's Disease
Brief summary
The purpose of this study is to assess the safety and efficacy of tulisokibart (MK-7240) in participants with moderately to severely active Crohn's Disease. After the completion of the 12-week Induction Period, eligible participants have the option to enter an Open-label Extension (OLE) Period for up to 170 weeks.
Interventions
BIOLOGICALTulisokibart
Tulisokibart administered by IV infusion as directed by the protocol
DIAGNOSTIC_TESTCompanion Diagnostic (CDx)
PRA023 CDx Genotyping Assay
Sponsors
Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants enrolling in the study are initially allocated to a single treatment arm in the Induction Period. Eligible participants who complete the Induction Period and responded to tulisokibart treatment may then enter the optional 170-week OLE Period. Participants who enter the OLE Period are randomized to one of two tulisokibart treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Crohn's disease (CD) * Moderately to severely active CD as defined by Crohn's disease activity index (CDAI) score and centrally read endoscopy * Must have corticosteroid dependence or have had no response, insufficient response, loss of response and/or intolerance to at least one of the following therapies: corticosteroid, immunosuppressants, or an approved anti-tumor necrosis factor (TNF), anti-integrin, or anti-interleukin (IL)12/23 * Able to provide written informed consent and understand and comply with the requirements of the study
Exclusion criteria
* Women of child bearing potential (WOCBP) and men with female partner of childbearing potential who are unwilling to use two highly effective methods of contraception to avoid pregnancy for the entire study period and up to 12 weeks after the last dose of study drug * Diagnosis of ulcerative colitis (UC) or indeterminate colitis * CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or illeal involvement * Suspected or diagnosed intra-abdominal or perianal abscess at screening * Current stoma or need for colostomy or ileostomy * Previous small bowel resection with a combined resected length of \>100 cm or previous colonic resection of \> 2 segments * Surgical bowel resection within 3 months before screening * Past or current evidence of definite low-grade or high-grade colonic dysplasia not completely removed * Participants in the opinion of the investigator are at an unacceptable risk for participation in the study * Participants who meet the protocol criteria for important laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Up to approximately 18 weeks | Number of participants who experienced treatment-emergent adverse events (AEs) |
| Serious Adverse Events | Up to approximately 18 weeks | Number of participants who experienced serious adverse events (SAEs) |
| Adverse Events Leading to Discontinuation | Up to approximately 12 weeks | Number of participants who experienced AEs leading to discontinuation |
| Endoscopic Improvement | Week 12 | Number of participants achieving induction of endoscopic improvement (decrease in simple endoscopy score for Crohn's disease \[SES-CD\] ≥ 50% from Baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission | Week 12 | Number of participants achieving clinical remission, as defined by Crohn's disease activity index \[CDAI\] score \< 150 |
| Endoscopic and Clinical Improvement | Week 12 | Number of participants who achieved a decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline or CDAI\<150 |
| Number of Participants Achieving Biomarker and Clinical Composite Improvement | Week 12 | Biomarker and clinical composite improvement is defined as a decrease by at least 50% in hsCRP or fecal calprotectin from baseline and a reduction of either CDAI ≥ 100 points from Baseline or CDAI\<150 in subjects with at least one elevated biomarker at baseline. |
| Normalization of C-reactive Protein | Week 12 | Number of participants with normalization of hsCRP (as defined by hsCRP \< 5 mg/L), among subjects with elevated concentrations at Baseline, at Week 12 |
| Normalization of Fecal Calprotectin | Week 12 | Number of participants with normalization of fecal calprotectin (fecal calprotectin \< 250 ug/g), among subjects with elevated concentrations at Baseline, at Week 12 |
| Clinical Response | Week 12 | Clinical response is defined as either a reduction of either CDAI ≥ 100 points from Baseline or CDAI\<150. |
| Two Component Patient-reported Outcome (PRO-2) Remission | Week 12 | Number of subjects with PRO-2 remission (defined as average daily abdominal pain score ≤ 1 point and average daily stool frequency ≤ 3 points with abdominal pain and stool frequency no worse than Baseline) at Week 12. |
| Change From Baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD) | Baseline and Week 12 | Assessment of change in simple endoscopy score for Crohn's Disease (SES-CD) from Baseline. Measure Description: The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease. |
| Serum Concentration of Tulisokibart | Week 12 | Blood samples were obtained for PK analysis of the serum concentration of tulisokibart at week 12. |
| Number of Participants Positive for Anti-drug Antibody (ADA) | Up to approximately 12 weeks | Blood samples were collected for the determination of anti-tulisokibart antibodies based on confirmatory assay. The number of participants with confirmed positive anti-tulisokibart antibodies results at any visit during the study is presented. |
| Number of Participants With Positive Neutralizing Anti-Bodies (NAB) | Up to approximately 12 weeks | Blood samples were collected for the determination of NAB. The number of participants with positive NAB results at any visit during the study is presented. |
Countries
Australia, Belgium, Canada, Czechia, France, Georgia, Poland, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Eligible participants were allocated to the open-label 12-week Induction Period to receive tulisokibart by intravenous infusion. Eligible participants who completed the Induction Period and responded to tulisokibart treatment may have continued into an optional 170-week Open-label Extension (OLE) Period. Participants who entered the OLE Period were randomized to receive tulisokibart at either 100 mg every 4 weeks (q4w) or 250 mg q4w.
Pre-assignment details
Safety (adverse event) analyses are reported based on the 12-week Induction Period and include protocol pre-specified safety monitoring beyond the Induction Period. Per protocol, efficacy analyses are reported based on the 12-week Induction Period.
Participants by arm
| Arm | Count |
|---|---|
| PRA023 Participants received PRA023 administered by intravenous (IV) infusion as directed by the protocol. | 55 |
| Total | 55 |
Baseline characteristics
| Characteristic | PRA023 |
|---|---|
| Age, Customized Age (years) 18-44 years | 37 Participants |
| Age, Customized Age (years) 45-64 years | 13 Participants |
| Age, Customized Age (years) 65+ years | 5 Participants |
| Baseline Crohn's disease activity index (CDAI) Score | 317.9 score STANDARD_DEVIATION 67.2 |
| Baseline Simple Endoscopic Score for Crohn's Disease (SES-CD) | 13.4 score STANDARD_DEVIATION 6.7 |
| Concomitant Immunomodulator Use | 8 Participants |
| Concomitant Oral Corticosteroid Use | 22 Participants |
| Duration of Disease (years) | 10.29 years STANDARD_DEVIATION 9.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Number of Prior Exposure to Biologic Therapy 1 Prior Biologic | 10 Participants |
| Number of Prior Exposure to Biologic Therapy 2 Prior Biologics | 10 Participants |
| Number of Prior Exposure to Biologic Therapy >=3 Prior Biologics | 19 Participants |
| Number of Prior Exposure to Biologic Therapy Biologic Naive | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 34 Participants |
| Weight | 77.6 kg STANDARD_DEVIATION 20.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 33 / 55 | 17 / 19 | 16 / 18 |
| serious Total, serious adverse events | 9 / 55 | 4 / 19 | 4 / 18 |
Outcome results
Primary
Adverse Events
Number of participants who experienced treatment-emergent adverse events (AEs)
Time frame: Week 12
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Adverse Events | 43 Participants |
Primary
Adverse Events Leading to Discontinuation
Number of participants who experienced AEs leading to discontinuation
Time frame: Week 12
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Adverse Events Leading to Discontinuation | 2 Participants |
Primary
Endoscopic Improvement
Number of participants achieving induction of endoscopic improvement (decrease in simple endoscopy score for Crohn's disease \[SES-CD\] ≥ 50% from Baseline)
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores with no important protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Endoscopic Improvement | 13 Participants |
Primary
Serious Adverse Events
Number of participants who experienced serious adverse events (SAEs)
Time frame: Week 12
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Serious Adverse Events | 8 Participants |
Secondary
Change From Baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD)
Assessment of change in simple endoscopy score for Crohn's Disease (SES-CD) from Baseline. Measure Description: The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Time frame: Baseline and Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores, who have SES-CD scores at Baseline and Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRA023 | Change From Baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD) | -2.6 score on a scale | Standard Deviation 4.32 |
Secondary
Clinical Remission
Number of participants achieving clinical remission, as defined by Crohn's disease activity index \[CDAI\] score \< 150
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Clinical Remission | 27 Participants |
Secondary
Clinical Response
Clinical response is defined as either a reduction of either CDAI ≥ 100 points from Baseline or CDAI\<150.
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Clinical Response | 37 Participants |
Secondary
Endoscopic and Clinical Improvement
Number of participants who achieved a decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline or CDAI\<150
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Endoscopic and Clinical Improvement | 9 Participants |
Secondary
Normalization of C-reactive Protein
Number of participants with normalization of hsCRP (as defined by hsCRP \< 5 mg/L), among subjects with elevated concentrations at Baseline, at Week 12
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores who have elevated hsCRP values at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Normalization of C-reactive Protein | 5 Participants |
Secondary
Normalization of Fecal Calprotectin
Number of participants with normalization of fecal calprotectin (fecal calprotectin \< 250 ug/g), among subjects with elevated concentrations at Baseline, at Week 12
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores with elevated fecal calprotectin at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Normalization of Fecal Calprotectin | 6 Participants |
Secondary
Number of Participants Achieving a Composite Response
Composite response is defined as a decrease by at least 50% in hsCRP or fecal calprotectin from baseline and a reduction of either CDAI ≥ 100 points from Baseline or CDAI\<150 in subjects with at least one elevated biomarker at baseline.
Time frame: Week 12
Population: All participants who have been treated with PRA023 with Baseline CDAI and SES-CD scores with at least one elevated biomarker at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Number of Participants Achieving a Composite Response | 17 Participants |
Secondary
Number of Participants Positive for Anti-drug Antibody (ADA)
Blood samples were collected for the determination of anti-PR023 antibodies based on confirmatory assay. The number of participants with confirmed positive anti-PR023 antibodies results at any visit during the study is presented.
Time frame: Up to approximately 12 weeks
Population: All participants who were treated with PRA023 with Baseline CDAI and SES-CD scores and had blood samples collected for ADA determination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Number of Participants Positive for Anti-drug Antibody (ADA) | 8 Participants |
Secondary
Number of Participants With Positive Neutralizing Anti-Bodies (NAB)
Blood samples were collected for the determination of NAB. The number of participants with positive NAB results at any visit during the study is presented.
Time frame: Up to approximately 12 weeks
Population: All participants who were treated with PRA023 with Baseline CDAI and SES-CD scores and who were ADA positive post-baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Number of Participants With Positive Neutralizing Anti-Bodies (NAB) | 8 Participants |
Secondary
Serum Concentration of PRA023 (MK-7240)
Blood samples were obtained for PK analysis of the serum concentration of PRA023 at week 12.
Time frame: Week 12
Population: All participants who were treated with PRA023 with Baseline CDAI and SES-CD scores, and had blood samples drawn for serum concentration of PRA023
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRA023 | Serum Concentration of PRA023 (MK-7240) | 88199.1 ng/mL | Standard Deviation 43811.21 |
Secondary
Two Component Patient-reported Outcome (PRO-2) Remission
Number of subjects with PRO-2 remission (defined as average daily abdominal pain score ≤ 1 point and average daily stool frequency ≤ 3 points with abdominal pain and stool frequency no worse than Baseline) at Week 12.
Time frame: Week 12
Population: All subjects who have been treated with PRA023 with Baseline CDAI and SES-CD scores.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRA023 | Two Component Patient-reported Outcome (PRO-2) Remission | 27 Participants |