A clinical study of tulisokibart in people with Crohn’s disease (MK-7240-006)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prometheus Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Nov 2021 → 25 Jun 2025

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509742-35-00

EudraCT number

2021-000092-37

WHO UTN

U1111-1309-6108

ClinicalTrials.gov

NCT05013905

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

• To evaluate the safety and tolerability of PRA023 following 12-weeks of induction therapy
• To assess the proportion of subjects with endoscopic improvement (decrease in simple endoscopy score for Crohn’s disease [SES-CD] ≥ 50% from Baseline) at Week 12

Secondary objectives 10

1. • To assess the proportion of subjects with clinical remission (Crohn’s disease activity index [CDAI] < 150) at Week 12
2. • To assess the proportion of subjects with endoscopy and clinical improvement (decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline) at Week 12
3. • To assess the proportion of subjects with biomarker and clinical improvement (decrease in high sensitivity C-reactive protein [hsCRP] or fecal calprotectin ≥ 50% from Baseline, among subjects with at least one elevated biomarker at Baseline, AND reduction in CDAI ≥ 100 points from Baseline) at Week 12
4. • To assess the proportion of subjects with normalization of C-reactive protein (hsCRP < upper limit of normal [ULN]), among subjects with elevated concentrations at Baseline, at Week 12
5. • To assess the proportion of subjects with normalization of fecal calprotectin (fecal calprotectin < ULN), among subjects with elevated concentrations at Baseline, at Week 12
6. • To assess the proportion of subjects with clinical improvement (reduction in CDAI ≥ 100 points from Baseline) at Week 12
7. • To assess the proportion of subjects with two component patient-reported outcome (PRO-2) remission (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)
8. • To assess the change in SES CD score from Baseline to Week 12
9. • To assess the pharmacokinetics (PK) of PRA023
10. • To assess the immunogenicity of PRA023

Conditions and MedDRA coding

Crohn's disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003556-PIP02-24

Plan to share IPD

Yes

IPD plan description

https://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female ≥ 18 years of age.
2. Subjects must have had a diagnosis of CD (confirmed by endoscopy + histology) at least 3 months prior to screening to be eligible for study participation. For subjects with no documented confirmation of CD diagnosis or if previous diagnosis is not deemed conclusive, CD diagnosis must be confirmed at time of screening colonoscopy. Note that mention of “chronic inflammation” or “Crohn’s disease” or equivalent on histology report is acceptable.
3. Moderately to severely active CD as defined by CDAI of ≥ 220 and ≤ 450.
4. SES-CD score (per central reading) ≥ 6 if ileocolonic or colonic disease; or ≥ 4 if isolated ileal disease only.
5. Subjects must satisfy at least one of the following criteria: a) In the past, had an inadequate response to one or more of the following treatments: • Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide ≥ 9 mg/day or equivalent or beclomethasone ≥ 5 mg/day for at least 2 weeks • Corticosteroid dependence as defined by failed to successfully taper to < 10 mg/day of prednisone equivalent (i.e., had a flare of disease) within 3 months of starting therapy, or if relapse occurs within 3 months of stopping corticosteroids • Immunosuppressants (azathioprine ≥ 2 mg/kg/day or 6 mercaptopurine ≥ 1.0 mg/kg/day, [or documentation of a therapeutic concentration of 6-thioguanine nucleotide] or methotrexate ≥ 15 mg/week) for at least 8 weeks. Note: a lower dosage of 6-MP or AZA is acceptable if local guidelines specify a different treatment regimen (which would need be documented in the source document) • An approved anti-TNF agent at an approved labeled dose for at least 8 weeks • An approved anti-integrin (e.g., vedolizumab) at an approved labeled dose for at least 8 weeks • An approved anti-IL-12/23 (e.g., ustekinumab) at an approved labeled dose for at least 8 weeks OR b) Had been intolerant to one or more of the above mentioned treatments (e.g., unable to achieve doses or treatment durations because of dose-limiting side effects [e.g., leukopenia, psychosis, uncontrolled diabetes, elevated liver enzymes]) OR c) Currently receiving one or more of the following treatments: • Oral Prednisone ≥ 10 mg/day (or equivalent) or budesonide ≥ 3 mg/day or beclomethasone ≥ 5 mg/day for at least 3 months • Immunosuppressants [azathioprine ≥ 2 mg/kg/day or 6 mercaptopurine ≥ 1.0 mg/kg/day, (or documentation of a therapeutic concentration of 6-thioguanine nucleotide)] for at least 8 weeks. Note: a lower dosage of 6-MP or AZA is acceptable if local guidelines specify a different treatment regimen (which would need be documented in the source document). Notes on subjects who have had prior approved biologic therapy(ies) (e.g., anti-TNF, anti-integrin, and/or anti-IL-12/23): • The study will include a maximum of 70% and a minimum of approximately 50% subjects who have had prior approved biologic therapy(ies) experience. Upon reaching the maximum number of allowed biologic experienced subjects (70%), subjects who have had prior biologic experience will no longer be allowed to enter the study. Upon reaching the maximum number of allowed biologic-naïve subjects (approximately 50%), subjects who have never been exposed to a prior biologic will no longer be allowed to enter the study. • Subjects cannot have had failed (no response, insufficient response, loss of response, and/or intolerance) > 4 approved biologic therapies, whether of same or different mechanism of action • Subjects previously on clinical trials only (i.e., did not receive commercial available therapy post-approval) are not considered to have received the approved therapy for purpose of this inclusion criteria.
6. For subjects who are women of childbearing potential (WOCBP) involved in any sexual intercourse that could lead to pregnancy, the subject has used two highly effective methods of contraception for at least 4 weeks prior to Day 1 and agrees to continue to use two highly effective methods of contraception until at least 12 weeks after the last dose of study drug.
7. Male subjects must use, with their female partner of childbearing potential, two highly effective methods of contraception and refrain from sperm donation from screening to 12 weeks after the last dose of study drug.
8. Subjects must meet drug stabilization requirements, as applicable: a) Oral corticosteroid treatment must be equivalent of ≤ 20 mg prednisone or ≤ 9 mg budesonide or beclomethasone ≤ 5 mg daily at a stable dose for at least 2 weeks prior to Day 1 b) Oral aminosalicylates should be at a stable dose for at least 2 weeks prior to Day 1 c) Azathioprine, 6-mercaptopurine, and methotrexate should be at a stable dose for at least 4 weeks prior to Day 1
9. Able to provide written informed consent and understand and comply with the requirements of the study.

Exclusion criteria 39

1. WOCBP and men with female partners of childbearing potential who are unwilling or unable to use two highly effective methods of contraception to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of study drug.
2. Women who are pregnant or breastfeeding.
3. Women with a positive pregnancy test on enrollment or prior to Day 1.
4. Diagnosis of ulcerative colitis or indeterminate colitis.
5. CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement.
6. Suspected or diagnosed intra-abdominal or perianal abscess at Screening.
7. Known symptomatic stricture or stenosis not passable in endoscopy (including pediatric colonoscope).
8. Current stoma or need for colostomy or ileostomy.
9. Previous small bowel resection with combined resected length of > 100 cm or previous colonic resection of > 2 segments.
10. Currently receiving total parenteral nutrition.
11. Surgical bowel resection within 3 months before screening.
12. Concomitant primary sclerosing cholangitis (PSC).
13. Past or current evidence of definite low-grade or high-grade colonic dysplasia that has not been completely removed.
14. Subjects who are scheduled or anticipate the need for surgery, aside from dermatologic procedures.
15. Subjects who have a history of clinically significant drug or alcohol abuse.
16. Concomitant illness that in the opinion of the Investigator, is likely to require systemic glucocorticosteroid therapy during the study (e.g., moderate to severe asthma).
17. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, pulmonary, cardiac, neurological, ophthalmologic, or cerebral disease. Concomitant medical conditions that in the opinion of the Investigator might place the subject at unacceptable risk for participation in this study.
18. Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to enrollment. Subjects with carcinoma in situ or localized cervical cancer, treated with definitive surgical intervention, are allowed.
19. Subjects at risk for tuberculosis (TB). Specifically, subjects with: a) A history of active TB b) Current clinical, radiographic, or laboratory evidence of active TB c) Latent TB which was not successfully treated. Subjects with a positive TB screening test indicative of latent TB will not be eligible for the study unless active TB infection has been ruled out, and an appropriate course of intervention for latent TB has been initiated at least 2 weeks prior to Day 1, and no evidence of active TB on chest x-ray during screening.
20. Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis).
21. Female subjects who have had a breast cancer screening that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
22. Subjects with any active infections (excluding fungal infections of nail beds) including, but not limited to, those that require IV antimicrobial treatment 4 weeks or oral antimicrobial treatment 2 weeks prior to randomization. Subjects with evidence of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection detected during screening are also excluded, but subjects with successfully treated Hepatitis C with no recurrence for ≥ 1 year are allowed. Subjects with active documented or suspected COVID-19 infection within 4 weeks of randomization or asymptomatic SARS-CoV-2 test positivity within 2 weeks of randomization are excluded.
23. Subjects with herpes zoster reactivation or cytomegalovirus (CMV) that resolved less than 2 months prior to signing informed consent.
24. Subjects who have received any live vaccines within 3 months of the anticipated first dose of study medication or who will have need of a live vaccine at any time during the study.
25. Positive stool Polymerase Chain Reaction (PCR) if Investigator deems this positivity reflects infection rather than colonization or positive culture for enteric pathogens.
26. Stool positive for Clostridium difficile (C. difficile) toxin. Subjects who are positive can be retested after the completion of a full course of treatment for C. difficile infection.
27. Any of the following lab values: a) Hemoglobin (Hgb) < 8.0 g/dL (80 g/L) b) White blood cell (WBC) < 2,500/mm^3 (2.5 x 10^9/L) c) Neutrophils < 1,000/mm^3 (1 x 10^9/L) d) Platelets < 100,000/mm^3 (100 x 10^9/L) d) Serum creatinine > 2 times ULN e) Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times ULN f) Any other laboratory test results that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.
28. Failed (no response, insufficient response, loss of response, and/or intolerance) > 4 approved biologic therapies (anti-TNF, anti-integrin, anti-IL12/23), whether of same or different mechanism of action.
29. Any marketed biologic within 8 weeks for anti-TNF agents and 12 weeks for anti-integrin agents (e.g., vedolizumab) and ustekinumab prior to Day 1 or if drug level per therapeutic dose monitoring is greater than lower limit of detection.
30. Any biologic immunomodulators used for CD or other conditions within 8 weeks or 5 half-lives, whichever is longer, prior to Day 1 or if drug level per therapeutic dose monitoring is greater than lower limit of detection.
31. Rituximab within 1 year prior to Day 1.
32. Parenteral corticosteroids within 4 weeks or rectal administration of corticosteroids within 2 weeks prior to Day 1.
33. Rectal administration of 5-ASA within 2 weeks prior to Day 1.
34. Tacrolimus, cyclosporine, mycophenolate mofetil (CellCept®), immunoadsorption columns (such as Prosorba columns), D Penicillamine, Leflunomide, Thalidomide, chronic use of non-steroidal anti-inflammatory agents (NSAIDs), and aspirin > 81 mg/day within 2 weeks prior to Day 1.
35. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of entry into the IP.
36. Prior exposure to PRA023.
37. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
38. Legal or mental incapacitation, or inability to understand and comply with the requirements of the study.
39. Known allergies, hypersensitivity, or intolerance to PRA023 or its excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Safety and tolerability: the proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values
2. • The proportion of subjects with endoscopic improvement, as defined by decrease in SES-CD ≥ 50% from Baseline at Week 12

Secondary endpoints 10

1. • The proportion of subjects in clinical remission (CDAI < 150) at Week 12
2. • The proportion of subjects with endoscopic and clinical improvement, as defined by decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline at Week 12
3. • The proportion of subjects with both biomarker and clinical improvement (decrease in hsCRP OR fecal calprotectin ≥ 50% from Baseline, among subjects with at least one elevated biomarker at Baseline, AND reduction in CDAI ≥ 100 points from Baseline) at Week 12
4. • The proportion of subjects with normalization of hsCRP (as defined by hsCRP < ULN), among subjects with elevated concentrations at Baseline, at Week 12
5. • The proportion of subjects with normalization of fecal calprotectin (as defined by fecal calprotectin < ULN), among subjects with elevated concentrations at Baseline, at Week 12
6. • The proportion of subjects in clinical response, as defined by reduction in CDAI ≥ 100 points from Baseline at Week 12
7. • The proportion 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
8. • Change in SES-CD score at Week 12 from Baseline
9. • Descriptive summaries of PK and immunogenicity of PRA023
10. • Proportion of subjects developing anti-drug antibody (ADA) and neutralizing antibody (Nab)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prometheus Biosciences Inc.

Sponsor organisation

Prometheus Biosciences Inc.

Address

3050 Science Park Road

City

San Diego

Postcode

92121-1102

Country

United States

Scientific contact point

Organisation

Prometheus Biosciences Inc.

Contact name

Regulatory Affairs

Public contact point

Organisation

Prometheus Biosciences Inc.

Contact name

Regulatory Affairs

Third parties 15

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications