JAKAHDI - JAK inhibitors in acquired hemophagocytic syndrome in the ICU

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Sep 2024 → ongoing

Decision date (initial)

2023-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministry of Health - PHRC-K22185

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that ruxolitinib, in association with standard of care, may reverse organ failure (as represented by SOFA score) better than standard of care alone in critically ill patients with acquired HS.

Secondary objectives 4

1. - To demonstrate that ruxolitinib may improve overall survival in HS critically ill patients
2. - To demonstrate that ruxolitinib may reverse clinical (temperature, SOFA score) and biological (ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, hemoglobin level, white blood cells count, platelets count) manifestations related to HS
3. - To analyse the impact of ruxolitinib on biological inflammatory markers (IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha)
4. - To demonstrate the safety of ruxolitinib in critically ill HS patients

Conditions and MedDRA coding

Adult patients older than 18 years. Patients admitted to the participating ICUs will be included in this study if the meet eligibility criteria.

Study design 1 period

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - adult patients older than 18 years
2. - acquired hemophagocytic syndrome, regardless of etiology, defined by the presence of 5 or 6 HLH-2004 criteria or HScore ≥ 200
3. - admission in the ICU
4. - need for symptomatic treatment of HS in relation with organ failure, as defined by SOFA score ≥ 4
5. - Informed consent signed: • by the patient, • Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent in written as per L1111-6,
6. - Or in an emergency situation and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow).
7. - The inclusion of women of childbearing potential requires the use of a highly effective contraceptive measure. Contraception should be maintained during treatment and one day after.

Exclusion criteria 13

1. - Moribund, defined by a life expectancy < 48 hours;
2. - Pregnant or lactating patients (women of childbearing potential must have a negative urine or blood Human Chorionic Gonadotropin pregnancy test prior to trial entry);
3. - No affiliation to health insurance;
4. - Known hypersensitivity to ruxolitinib;
5. - Lactose intolerance;
6. - Hypersensitivity to cellulose, microcrystalline; magnesium stearate; silica, colloidal anhydrous; sodium starch glycolate (Type A); povidone K30; hydroxypropylcellulose 300 to 600 cps,
7. - Pre-existing decisions of withholding/withdrawing care,
8. - History of progressive multifocal leukoencephalopathy
9. - Uncontrolled cutaneous cancer
10. - Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up
11. - Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
12. - Patients deprived of their liberty by a judicial or administrative decision
13. - Participation in another interventional research

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary end point will be survival with a decrease in SOFA score ≥ 3 points at day 7.

Secondary endpoints 4

1. - Overall survival in HS critically ill patients
2. - Temperature, SOFA score and biological (ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, hemoglobin level, white blood cells count, platelets count) manifestations related to HS
3. - To analyse biological inflammatory markers (IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha)
4. - Safety of ruxolitinib in critically ill HS patients

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Sandrine VALADE

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Sandrine VALADE

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 22 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