Orismilast for the treatment of moderate to severe ulcerative colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hvidovre Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Nov 2023 → 11 Feb 2025

Decision date (initial)

2023-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

UNION Therapeutics A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To explore evidence of efficacy of orismilast in the oral treatment of patients with UC when dosed twice daily for up to 12 weeks in a clinically relevant endpoint.

Secondary objectives 3

1. To add depth and detail to the primary objective using Total Mayo score and validated biomarker measures
2. To explore the impact of orismilast on patient reported quality of life
3. To investigate the safety and tolerability of orismilast in the oral treatment of patients with UC when applied twice daily for up to 12 weeks

Conditions and MedDRA coding

ulcerative colitis

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female adult patients, 18 years of age or older. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 that result in a low failure rate of less than 1% per year when used consistently and correctly, for the duration of the trial and 16 weeks after last administration. A list of contraception methods meeting these criteria is provided in the patient information and Appendix E
2. Diagnosis of ulcerative colitis with a minimum of 3 months of disease history
3. Mayo endoscopic subscore of 2 or 3 at screening
4. Current treatment regimen of 5-ASA (e.g., mesalazine and sulfazalazine), mercaptopurine (6-MP), methotrexate (MTX), or azathioprine
5. Currently on stable unchanged medication regimen for the last 3 months or more, but now requiring intensification (dose-increase or additional therapy)
6. Signed and dated written informed consent in accordance with GCP and local legislation prior to the start of any screening procedures

Exclusion criteria 11

1. Require hospitalization
2. Clinical signs suggestive of fulminant colitis or toxic megacolon
3. Currently treated with biologic therapy
4. Currently treated with steroids
5. Failed on >1 anti-body treatment
6. Treated with any therapies and systemic treatments as described in Table 3, “Prohibited Prior Therapies and Treatments” that do not comply with the indicated washout interval
7. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Women who stop nursing before the study drug administration do not need to be excluded from participating
8. Treatment with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug, whichever is longer, prior to screening
9. History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients
10. HADS score ≥15 at baseline in the depression subscore
11. Any medical or psychiatric condition that, in the Investigator’s opinion, would preclude the patient from adhering to the protocol, completing the study per-protocol, and/or would place the patient at unacceptable risk while receiving the investigational therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with clinical remission on Total Mayo score at Week 12, defined as 2 points or lower, with no individual sub-score exceeding 1 point

Secondary endpoints 8

1. Percent change in levels of high-sensitivity c reactive protein from baseline at Week 2, 4, 6 and Week 12
2. Percent change in levels of fecal calprotectin from baseline at Week 2, 4, 6 and Week 12
3. Proportion of patients with endoscopic improvement at Week 12, defined by Mayo endoscopic subscore of 0 or 1, without friability
4. Change from baseline in two specific items from the total Mayo score (stool frequency and rectal bleeding) known as PRO2 at Week 12
5. Clinical response at Week 12, defined as decrease from baseline in Total Mayo score by ≥3 points and at least 30%, with decrease in rectal bleeding subscore of ≥1
6. Short Inflammatory Bowel Disease Questionnaire (sIBDQ) change from baseline at Week 2, 4, 6 and Week 12
7. HADS (Hospital Anxiety and Depression Scale) change from baseline at Week 12
8. Occurrence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) at any time during the study

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hvidovre Hospital

Sponsor organisation

Hvidovre Hospital

Address

Kettegaard Alle 3

City

Hvidovre

Postcode

2650

Country

Denmark

Scientific contact point

Organisation

Hvidovre Hospital

Contact name

Johan Burisch

Public contact point

Organisation

Hvidovre Hospital

Contact name

Johan Burisch

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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