A Phase 2a Study of the Safety and Efficacy of OD-07656 and of Subsequent Vedolizumab Therapy in Moderately to Severely Active Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odyssey Therapeutics 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

28 Aug 2025 → ongoing

Decision date (initial)

2025-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety and tolerability of OD-07656 in participants with moderately to severely active UC; To evaluate the efficacy of OD-07656 in participants with moderately to severely active UC

Secondary objectives 2

1. To evaluate clinical outcomes following treatment with OD 07656 in participants with moderately to severely active UC
2. To evaluate clinical outcomes of vedolizumab treatment, following OD-07656 in participants with moderately to severely active UC

Conditions and MedDRA coding

Moderately to Severely Active Ulcerative Colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adults between 18 (or the minimum age of consent, if different locally) and 75 years of age, at the time of the Screening Visit
2. A diagnosis of UC extending ≥15 cm from the anal verge, established at least 90 days prior to the Screening Visit by clinical and endoscopic evidence of UC (colonoscopy or flexible sigmoidoscopy) and confirmed by histology
3. Moderately to severely active UC, defined as a 3 component MMCS of 5 to 9 points, with RBS ≥1 and MES ≥2 scored centrally
4. A participant must have a colonoscopy or a flexible sigmoidoscopy during the Screening Period. Participants may receive a flexible sigmoidoscopy unless a participant has had extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration. For these participants, a colonoscopy will be required if their last colonoscopy was more than 1 year before the Screening Visit. If the last colonoscopy was less than 1 year before the Screening Visit, then the participant may receive a flexible sigmoidoscopy
5. Demonstrated, in the opinion of the Investigator, an inadequate response, loss of response, or intolerance/medical contraindication to at least 1 of the following treatments as defined in the table below: oral aminosalicylates, corticosteroids, immunosuppressants (i.e., conventional therapies) or biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate (S1P) modulators (i.e., ATs).
6. Participants who are a person of childbearing potential (POCBP) must have a negative serum pregnancy test at the Screening Visit and a negative urine/serum pregnancy test at Day 1 prior to receiving study intervention. Participants unable to bear children must have documentation of such in the source records. Refer to the full protocol for definitions and specific requirements related to contraception and pregnancy prevention.
7. Capable of providing signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, including electronic data capture methods.

Exclusion criteria 20

1. Presence of the following: • Acute severe UC, defined by ≥6 bloody diarrhea/day and any signs of systemic toxicity (pulse >90 beats/min, temperature >37.8 °C, hemoglobin <105 g/L, erythrocyte sedimentation rate >30 mm/h, or C-reactive protein [CRP] >30 mg/L); or in the Investigator’s opinion, hospitalization for the treatment of UC may be imminent. • Previous extensive colonic resection (subtotal or total colectomy). • Short bowel syndrome. • Ileostomy, colostomy, ileoanal pouch, fistulae, or known fixed symptomatic stenosis of the intestine. • Toxic megacolon.
2. Current diagnosis of Crohn’s disease, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug (NSAID)-induced colitis, idiopathic colitis (i.e., colitis not consistent with UC), radiation colitis, microscopic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption
3. Participants with disease limited to the rectum (ulcerative proctitis) at the Screening Visit
4. Uncontrolled primary sclerosing cholangitis
5. Malignancies or history of malignancy within 5 years of the Screening Visit, except for adequately treated or completely excised nonmetastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ
6. History of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly
7. Systemic or opportunistic infections: • A positive diagnostic tuberculosis (TB) test (defined as a positive QuantiFERON test). In cases where the QuantiFERON test is indeterminate, the participant may have the test repeated once and if their second test is negative, they will be eligible. In the event a second test is also indeterminate, or QuantiFERON is unavailable, the Investigator has the option to perform a purified protein derivative (PPD) skin test. If the PPD reaction is <5 mm, then the participant is eligible. If the reaction is ≥5 mm, or PPD testing is not done, the participant is not eligible. An exception is made for participants with a history of latent TB who have documentation of completing ≥6 months of locally approved treatment for latent TB within 10 years prior to the first dose of study intervention. NOTE: Chest X-Ray during the Screening Period, read by a qualified radiologist, must be negative for findings suggestive of active TB (e.g., pulmonary infiltration, hilar adenopathy, granuloma(s), or pleural thickening). • A positive test for hepatitis B virus (HBV), as defined by the presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test. NOTE: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if no HBV deoxyribonucleic acid (DNA) is present, confirmed by HBV DNA polymerase chain reaction (PCR) reflex testing performed by the central laboratory. • A positive test for hepatitis C virus (HCV), as defined by a positive HCV antibody (Ab) test and detectable HCV ribonucleic acid (RNA). NOTE: Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks prior to Day 1]). • A positive test for serum human immunodeficiency virus (HIV) as defined by a positive serum HIV Ab test. • Evidence of Clostridioides difficile toxin, Escherichia coli (pathogenic), Salmonella, Shigella, Campylobacter, or Yersinia species or treatment for C. difficile infection, listeriosis, or other intestinal bacterial or parasitic pathogen, within 4 weeks prior to the Screening Visit, or a positive test for any of the above pathogens performed at screening. NOTE: Participants will be allowed to qualify at least 4 weeks after completion of antimicrobial treatment and have documentation of negative tests on 2 consecutive stool samples at least 3 days apart. • Has or ever has had any serious opportunistic infection (e.g., cytomegaloviral colitis, Pneumocystis carinii, aspergillosis, histoplasmosis). • Any other clinically significant extra-intestinal infection or opportunistic, chronic, or recurring infection within 6 months prior to Day 1, including, but not limited to infections requiring IV antibiotics (e.g., sepsis), hospitalization, or prolonged anti-infective treatment.
8. History of any major neurologic disorder or progressive multifocal leukoencephalopathy (PML), or signs/symptoms of any active cerebral/meningeal disease at the Screening Visit.
9. Hypersensitivity or allergy to vedolizumab or any other contraindication to vedolizumab, or any of its excipients
10. Hypersensitivity or allergy to OD 07656, or any of its excipients
11. Received any of the following: •Cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 56 days prior to Day 1. • IV corticosteroids within 14 days prior to Day 1. • Any biologic therapy (e.g., anti-tumor necrosis factors, anti-integrins, anti-interleukins) within 56 days or 5 half lives (whichever is greater) or within 28 days for participants without detectable drug levels prior to Day 1. • JAK inhibitors (e.g., tofacitinib, filgotinib, or upadacitinib) within 28 days prior to Day 1. • S1P modulators (i.e., ozanimod or etrasimod) within 28 days prior to Day 1. • IV antibiotics within 56 days prior to Day 1 or expected to receive IV antibiotics during the study. • NSAIDs as long-term treatment, defined as use for at least 4 days a week consistently each week over a period of at least a month (or acetaminophen >1000 mg daily and aspirin >325 mg daily). • Vaccination with a live or live-attenuated vaccine within 28 days prior to Day 1 or during the study. NOTE: It is recommended that participants be up to date for recommended inactivated, toxoid, or biosynthetic vaccines, such as injectable, coronavirus disease of 2019 (COVID 19), influenza, pneumococcal, and pertussis vaccine. • Fecal microbiota transplant (includes human microbiota-based therapeutics) within 28 days prior to Day 1. • Oral or injectable anticoagulants including but not limited to warfarin, heparin or heparinoids (i.e., enoxaparin), or direct acting anticoagulants such as Factor Xa inhibitors (i.e., apixaban, fondaparinux, and rivaroxaban) within 14 days prior to Day 1. • Oral corticosteroids: any doses >20 mg/day prednisone within the last 28 days, or for doses ≤20 mg/day prednisone, has not been on a stable dose for ≥28 days prior to Day 1. • Oral budesonide dose >9 mg/day within the last 28 days, or for doses ≤9 mg/day, has not been on a stable dose for ≥28 days prior to Day 1. • Oral 5-aminosalicylic acid drugs or sulfasalazine: any doses >4.8 g/day within the last 28 days or for doses ≤4.8 g/day, has not been on a stable dose for ≥28 days prior to Day 1. • Purine analogues (e.g., AZA, 6-MP, thioguanine) or MTX have been discontinued within 28 days prior to Day 1.
12. Laboratory results that meet the following limits: Parameter Exclusion AST or ALT >2 × ULN eGFR <30 mL/min/1.73 m2 (by MDRD or by Schwartz a) WBC <2500/μL (<2.5 GI/L) ANC <1200/μL (<1.2 GI/L) Platelet count <100,000/μL (<100 GI/L) Absolute lymphocyte count <750/μL (<0.75 GI/L) Hemoglobin <9 g/dL (<90 g/L) Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; ULN, upper limit of normal; WBC, white blood cell. a eGFR will be calculated using the MDRD equation for participants ≥18 years old. The Schwartz equation will be used for participants <18 years old.
13. Concurrent or previous participation in another clinical trial and received investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to Day 1
14. Any major surgery, in the Investigator’s opinion, performed within 8 weeks prior to Day 1 or planned during the study (i.e., any surgical procedure requiring general anesthesia).
15. Currently breastfeeding or planning to breastfeed during the study
16. History of excessive alcohol consumption or drug abuse that in the opinion of the Investigator may interfere with the participant’s ability to comply with the study procedures.
17. Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, investigational product administration, or may interfere with the interpretation of study results, as determined by the Investigator
18. Prior enrollment in the current study and had received treatment with OD 07656.
19. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling).
20. Is performing mandatory military service, deprived of liberty, in a residential care institution, or due to a judicial decision cannot take part in a clinical study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest and treatment discontinuations due to TEAEs
2. Changes in clinical laboratory parameters, electrocardiogram parameters, and vital signs
3. Change from baseline in 3-component modified Mayo Clinic Score (MMCS) (defined as sum of stool frequency subscore [SFS], rectal bleeding subscore [RBS], and Mayo endoscopic subscores [MES]a) at Week X

Secondary endpoints 3

1. Proportion of participants who achieve clinical remission defined as 3‑component MMCS ≤2 (SFS ≤1, RBS = 0, and MES ≤1) at Week X
2. Proportion of participants who have a clinical response per 3 component MMCS (defined as a decrease from baseline of ≥2 points and ≥30%, and either a decrease in RBS of ≥1 point or an absolute RBS of 0 or 1) at Week X
3. Proportion of participants who achieve clinical remission per MMCS at Week X

Investigational products

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

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odyssey Therapeutics Inc.

Sponsor organisation

Odyssey Therapeutics Inc.

Address

51 Sleeper Street

City

Boston

Postcode

02210-1276

Country

United States

Scientific contact point

Organisation

Odyssey Therapeutics Inc.

Contact name

Clinical Operations Development

Public contact point

Organisation

Odyssey Therapeutics Inc.

Contact name

Clinical Operations Development

Third parties 15

Locations

7 EU/EEA countries · 18 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 145 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