A Phase 4 Mechanistic Longitudinal Study to Evaluate the Impact of EARLY Risankizumab Treatment on TRM Cell Levels in Moderate-to-Severe Psoriasis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Icr Medical S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-08-12

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To determine whether early treatment with risankizumab (within ≤1 year since the onset of psoriasis symptoms) more effectively targets resident memory T cells compared to later treatment (after >10 years since the onset of psoriasis).

Secondary objectives 4

1. 1. To evaluate whether early treatment with risankizumab results in a higher percentage of patients achieving complete clearance and near complete clearance of psoriasis (PASI 0 and PASI≤ 1) compared to late intervention, measured at weeks 4, 16, 28, 40, and 52.
2. 2. To explore the impact of early versus late treatment with risankizumab on the number of epidermal CD8+CD103+ TRM cells at various time points (weeks 16 and 52) compared to baseline.
3. 3. To explore the reduction of systemic inflammatory biomarkers and cardiovascular associated biomarkers at weeks 16 and 52 in both early and late treatment.
4. 4. To assess the incidence of safety events in patients receiving at least one dose of risankizumab over a 60-week period.

Conditions and MedDRA coding

Psoriasis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. 2. Participant must be at least 18 years of age at the time of signing the informed consent.
3. 3. Participants who have plaque psoriasis candidate for RZB according to EU SmPC5, (a severity of PASI greater than or equal to 5 [PASI ≥5], a static physician global assessment greater than or equal to 3 [sPGA≥3] a Body Surface Area (BSA) affected of more than a 10%, and without diagnosed psoriatic arthritis). Arm 1 (Early treatment Group): Subjects must have new-onset plaque psoriasis, defined as the appearance of the first psoriasis plaques within the last 12 months before inclusion. Additionally, these participants must be naïve to any previous systemic treatment (including phototherapy). Arm 2 (Late treatment Group): Subjects must have plaque psoriasis of more than 10 years of duration at the time of inclusion and must be naïve to any biologic or advanced oral therapy.
4. 4. If female, subject must be either postmenopausal or practicing a birth control method described in the protocol
5. Laboratory values meeting the following criteria within the screening period prior to the first dose of study drug: • Serum aspartate transaminase (AST) < 2 × ULN; • Serum alanine transaminase (ALT) < 2 × ULN; • Serum direct bilirubin ≤ 2.0 mg/dL; except for subjects with isolated elevation of indirect bilirubin relating to a confirmed diagnosis of Gilbert syndrome; • Total white blood cell (WBC) count > 3,000/μL; • Absolute neutrophil count (ANC) > 1,500/μL; • Platelet count > 100,000/μL; • Hemoglobin > 10.0 g/dL (100 g/L); • Serum Triglycerides < 400 mg/dL; • Estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR [CKD-EPI]) ≥ 30 mL/min/1.73 m2.
6. 5. Participants must demonstrate the ability to adhere to all scheduled study visits and procedures.

Exclusion criteria 14

1. 1. Hypersensitivity to the active substance or to any of the excipients of risankizumab.
2. 2. Presence of any concurrent illness, which in the opinion of the investigator, would place the patient at unnecessary safety risk during the trial or interfere with completion of the trial.
3. 3. Erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.
4. 4. Active skin disease other than psoriasis that could interfere with the assessment of psoriasis.
5. 5. Any active infections including HIV, viral hepatitis (hepatitis B, hepatitis C), and/ or active tuberculosis. Subjects with a positive QuantiFERON®-TB /PPD test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. If the presence of latent tuberculosis is confirmed, then tuberculosis prophylaxis treatment must have been initiated and maintained according to local country guidelines. The patient will not be eligible for randomization if latent tuberculosis is present and is untreated as per local guidelines.
6. 6. Treatment with topical medications for psoriasis in the past 2 weeks.
7. 7. For arm 2: Treatment with oral systemic classic medications (including phototherapy) for psoriasis in the past 4 weeks or 5 times of half-lives (whichever is longer).
8. 8. Received a live vaccine within 6 weeks of start of RZB treatment.
9. 9. Participation in any other interventional clinical trial.
10. 10. History of any documented active or suspected malignancy or history of any malignancy within the last 5 years except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.
11. 11. Breastfeeding or pregnant women, or women who plan to become pregnant during study period.
12. 12. History of clinically significant (per Investigator's judgment) drug or alcohol abuse within the last 6 months.
13. 13. History of inflammatory bowel disease or diagnosed psoriatic arthritis.
14. 14. History of underlying medical diseases or problems including but not limited to the following: • Subject has been a previous recipient of a solid organ transplant that requires continuous immunosuppression. • Recent (within past 6 months) cerebrovascular accident or myocardial infarction • Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and ECG), or laboratory value at the screening visit outside the given range that, in the opinion of the investigator, is clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data. • No major surgery performed within 12 weeks prior to randomization or planned to be performed during the conduct of the trial (e.g., hip replacement, aneurysm removal, stomach ligation) as assessed by the Investigator. • History of suicidal ideation or attempts in the past 6 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in the number of epidermal and dermal CD8+CD103+ TRM cells at week 16 (compared to baseline lesional levels) in moderate to severe psoriasis patients treated with per label doses of risankizumab in early versus late treatment.

Secondary endpoints 4

1. 1. The percentage of patients with PASI 0 (complete clearance) at weeks 4, 16, 28, 40, and 52 in patients treated with per label doses of risankizumab in early versus late treatment. The percentage of patients with PASI ≤ 1 at weeks 4, 16, 28, 40, and 52 in patients treated with per label doses of risankizumab in early versus late treatment.
2. 2. The change in the number of epidermal and dermal CD8+CD103+ TRM cells at week 16 (compared to baseline non-lesional levels) in psoriasis patients treated with per label doses of risankizumab in early versus late treatment. The reduction in the number of epidermal and dermal CD8+CD103+ TRM cells at week 52 (compared to baseline lesional and non-lesional levels) in psoriasis patients treated with per label doses of risankizumab in early versus late treatment.
3. 3. Reduction of systemic inflammatory and CV associated biomarkers vs baseline levels at weeks 16 and 52 in early versus late treatment.
4. 4. Safety events from week 0 to week 60 in patients receiving at least one dose of risankizumab.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Icr Medical S.L.

Sponsor organisation

Icr Medical S.L.

Address

Calle Columela 9

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Icr Medical S.L.

Contact name

Dr. Álvaro González Cantero

Public contact point

Organisation

Icr Medical S.L.

Contact name

Dr. Álvaro González Cantero

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 5 files

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

Application history

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