Effect of Tofacitinib on coagulation and platelet function, and its role in thromboembolic events

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Princesa

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

1 Jun 2022 → ongoing

Decision date (initial)

2024-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518434-83-01

EudraCT number

2021-002211-65

ClinicalTrials.gov

NCT05313620

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Evaluate the effect of tofacitinib on platelet function and coagulation in patients with ulcerative colitis.

Secondary objectives 3

1. Evaluate the in vivo effect of tofacitinib on procoagulant status (platelet function and coagulation) in patients with UC over time.
2. Determine determine if there is a specific effect of tofacitinib on the hemostasis of UC patients treated with this drug compared to biologic drugs for UC.
3. Create a repository of biological samples (serum, plasma, nucleic acids, RNA, feces and urine) from a cohort of patients with UC (before and after treatment with tofacitinib or an anti-TNFα) that will be used in future complementary studies.

Conditions and MedDRA coding

ulcerative colitis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Over 18 years old.
2. Diagnosis of UC according to the criteria of the European Crohn’s and Colitis Organisation (ECCO).
3. Have indication of treatment with anti-TNFα (infliximab, adalimumab or golimumab) o tofacitinib
4. Be the first received JAK-inhibitor or anti-TNFα with a given mechanism of action.
5. Have endoscopic activity of UC within 1 month of starting the treatment (Mayo endoscopic sub-index of ≥ 2).
6. women of childbearing age using contraceptive methods with an error rate <1% per year. Examples of contraceptive methods whose error rate is <1% per year are: 1. Intrauterine device (IUD). 2. Bilateral tubal occlusion. 3. Couple with vasectomy. 4. Sexual abstinence.

Exclusion criteria 16

1. Under 18 years old.
2. Have previously received a drug with the same mechanism of action (anti-TNFα or JAK-inhibitors)
3. Medical history of thromboembolic events.
4. Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation.
5. Use of combined hormonal contraceptives or hormone replacement therapy.
6. Hereditary coagulation disorders.
7. Refusal to give consent for participation in the study.
8. Immune-mediated disease.
9. Neoplasm or active infection.
10. Pregnancy or lactation.
11. Alcohol or drug abuse.
12. Ostomy.
13. Colectomy.
14. Active infection with hepatitis B, C or HIV virus.
15. Indication of anti-TNFα or JAK-inhibitors treatment for a cause other than UC.
16. abdominal surgery in the last 6 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Platelet activation status will be assessed ex vivo in platelet-rich plasma (PRP) samples from UC patients (active and quiescent) and healthy controls incubated in the absence or presence of drug (tofacitinib or anti-TNFα). Regarding the in vivo study, platelet activation will be analyzed in samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα. It will be mesured by rate of platelet agregation

Secondary endpoints 3

1. Endoscopic activity will be evaluated by the Mayo endoscopic sub-score; endoscopic activity will be considered as ≥ 2.
2. Endoscopic response will be defined as a decrease of ≥ 1 point in the Mayo endoscopic sub-score 3 months after starting treatment.
3. Endoscopic remission will be defined as an endoscopic subscore ≤1, 3 months after starting treatment.

Investigational products

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

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Princesa

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Princesa

Address

Calle De Diego De Leon 62

City

Madrid

Postcode

28006

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Princesa

Contact name

Ana Garre

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Princesa

Contact name

Ana Garre

Locations

1 EU/EEA country · 1 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 11 files

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

Application history

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