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icotrokinra
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Icotrokinra – Overview of ICONIC-TOTAL Clinical Trial
Last Updated: 08/22/2025
SUMMARY
- Icotrokinra (JNJ-77242113) is a targeted oral peptide that selectively binds the interleukin-23 (IL-23) receptor and inhibits IL-23 pathway signaling.1
- Icotrokinra is being studied in five plaque psoriasis (PsO) phase 3 clinical trials (ICONIC-LEAD, ICONIC-TOTAL, ICONIC ADVANCE-1, ICONIC ADVANCE-2, ICONIC-ASCEND).2
- 6 - ICONIC-TOTAL is an ongoing, phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled study (NCT06095102) evaluating the efficacy and safety of icotrokinra 200 mg daily in patients ≥12 years of age with plaque PsO and high-impact site involvement.1,
2 - At week 16, the primary endpoint for Investigator’s Global Assessment (IGA) score of 0/1 and ≥2-grade improvement from baseline was achieved by significantly more patients receiving icotrokinra (57%) compared to patients receiving PBO (6%; P<0.001).1
- At week 16, the major secondary endpoints of scalp-specific IGA [ss-IGA] 0/1, was achieved by 66% of patients receiving icotrokinra compared to 11% of patients receiving PBO (P<0.001), static Physician’s Global Assessment of Genitalia [sPGA-G] 0/1 was achieved by 77% of patients receiving icotrokinra compared to 21% of patients receiving PBO (P<0.001), and Physician’s Global Assessment of hands and feet [hf-PGA] 0/1 was achieved by 42% of patients receiving icotrokinra compared to 26% of patients receiving PBO.
- Through week 16, 50% of patients receiving icotrokinra and 42% of patients receiving PBO reported ≥1 adverse event (AE). No new safety signals were identified through week 16.1
CLINICAL DATA
ICONIC-TOTAL
Gooderham et al (2025)1 reported results through week 16 from ICONIC-TOTAL, a phase 3 clinical trial evaluating the efficacy and safety of icotrokinra compared to PBO for the treatment of adults and adolescents (≥12 years of age) with plaque PsO and high-impact site involvement.
Study Design/Methods
- Key inclusion criteria are as follows:1,2
- Adults and adolescents (≥12 years of age) with a diagnosis of plaque PsO for ≥26 weeks (with or without psoriatic arthritis [PsA]) who were candidates for phototherapy or systemic therapy and failed ≥1 topical therapy
- Total body surface area (BSA) ≥1%, and IGA ≥2 at screening and baseline
- Involvement of ≥1 high-impact site with at least moderate severity:
- Scalp with ss-IGA ≥3
- Genital with sPGA-G ≥3
- Hand/Foot with hf-PGA ≥3
- Key exclusion criteria are as follows:2
- Nonplaque form of PsO (eg, erythrodermic, guttate, or pustular)
- Drug-induced PsO
- Severe, progressive or uncontrolled renal, liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disease
- Patients with palmoplantar pustulosis of the palmoplantar area (if hf-PGA ≥3 at baseline) or dermatoses (other than plaque PsO)
- Adult and adolescent patients were randomized in a 2:1 ratio to receive icotrokinra
200 mg oral (PO) or PBO once daily with PBO crossover to icotrokinra at week 16.1 - Safety will be evaluated through week 1601
- The primary and select key secondary outcome measures are described in Table: ICONIC-TOTAL Key Clinical Trial Outcome Measures at Week 16.1,2
| Primary Endpoint |
|---|
| Percentage of patients who achieved an IGA score of cleared (0) or minimal (1) and ≥2-grade improvement from baseline |
| Key Secondary Endpoints |
| Percentage of patients who achieved IGA score of cleared (0) |
| Percentage of patients who achieved ss-IGA score of absence of disease (0) or very mild disease (1) |
| Percentage of patients who achieved sPGA-G score of clear (0) or minimal (1) |
| Percentage of patients who achieved hf-PGA score of clear (0) or almost clear (1) |
| Percentage of patients who achieved PSSI 90 response |
| Percentage of patients who achieved PSSD Symptom Score of 0 |
| Percentage of patients who achieved ≥4-point improvement from baseline in Scalp Itch NRS score |
| Note: Additional details regarding study outcome definitions can be found on clinicaltrials.gov. Abbreviations: hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment; PGA, Physician’s Global Assessment; NRS, numeric rating scale; PSSD, Psoriasis Symptom and Sign Diary; PSSI, Psoriasis Scalp Severity Index; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment. |
Results
Patient Characteristics
- A total of 311 (icotrokinra, n=208; PBO, n=103) patients were included in the study. Baseline characteristics are described in Table: Baseline Demographics and Clinical Characteristics.1
| Icotrokinra 200 mg QD (n=208) | Placebo (n=103) | |
|---|---|---|
| Demographics | ||
| Age, years, mean (SD) | 45.3 (14.6) | 43.5 (13.8) |
| Male, % | 66 | 61 |
| White, % | 77 | 80 |
| BMI, kg/m2, mean (SD)a | 29.0 (6.6) | 29.4 (8.1) |
| Disease Characteristics | ||
| PsO disease duration, years, mean (SD) | 16.8 (13.3) | 15.2 (10.5) |
| % BSA with PsO, mean (SD) | 16.6 (13.5) | 14.8 (11.7) |
| <10% | 36 | 37 |
| ≥10% | 64 | 63 |
| IGA score, moderate (3), % | 74 | 71 |
| IGA score, severe (4), % | 22 | 21 |
| PASI (0-72), mean (SD) | 14.6 (7.6) | 14.0 (7.0) |
| Previous Therapy, % | ||
| Phototherapy (PUVA and UVB) | 43 | 31 |
| Systemic therapyb | 73 | 73 |
| Biologic therapyc | 34 | 31 |
| High-Impact Site PsO Severityd | ||
| ss-IGA score ≥3, n (%) | 167 (80) | 85 (83) |
| moderate (3), % | 80 | 75 |
| severe (4)b, % | 20 | 25 |
| sPGA-G score ≥3, n (%) | 98 (47) | 42 (41) |
| moderate (3)b, % | 77 | 69 |
| severe (4), % | 22 | 29 |
| very severe (5), % | 1 | 2 |
| hf-PGA score, ≥3, n (%) | 48 (23) | 23 (22) |
| moderate (3), % | 65 | 83 |
| severe (4), % | 35 | 17 |
| Abbreviations: BMI, body mass index; BSA, body surface area; hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PGA, Physician’s Global Assessment; PsO, psoriasis; PUVA, psoralen plus ultraviolet A; QD, once daily; SD, standard deviation; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment; UVB, ultraviolet B aIcotrokinra: n=203; Placebo: n=101 bIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, biologics. cIncludes adalimumab, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, etanercept, guselkumab, infliximab, ixekizumab, natalizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab dPsO involving high-impact sites was not mutually exclusive | ||
Efficacy
- The key clinical endpoints are described in Table: Key Clinical Endpoints at Week 16.
1
| % (n/N) | Icotrokinra 200 mg QD | Placebo |
|---|---|---|
| Proportion of patients achieving: | ||
| IGA 0/1 and ≥2-grade improvement from baseline | 57 (118/208); P<0.001a,b | 6 (6/103) |
| IGA 0 | 25 (53/208); P<0.001b | 1 (1/103) |
| ss-IGA 0/1c | 66 (110/167); P<0.001d | 11 (9/85) |
| sPGA-G 0/1c | 77 (75/98); P<0.001d | 21 (9/42) |
| hf-PGA score 0/1c | 42 (20/48)e | 26 (6/23) |
| ss-IGA 0c | 49 (82/167); Nominal P<0.001d,f | 2 (2/85) |
| sPGA-G 0c | 62 (61/98); Nominal P<0.001d,f | 10 (4/42) |
| PSSD Symptom Score of 0g | 16 (31/191); P<0.01b | 3 (3/87) |
| PSSI 90h | 57 (96/167); P<0.01i | 6 (5/85) |
| CMI in Scalp Itch NRSj | 59 (77/131); P<0.01i | 9 (5/58) |
| Abbreviations: BSA, body surface area; CI, confidence interval; CMI, clinically meaningful improvement (≥4-point improvement from baseline); hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment; NRS, numeric rating scale; PSSI, Psoriasis Scalp Severity Index; PSSI 90, reduction from baseline of ≥90% in the PSSI score; QD, once daily; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment aPrimary endpoint; Treatment difference of 51.1% (95% CI, 42.1-58.8); Treatment difference and 95% CI (using Miettinen-Nurminen method) were calculated adjusting for high-impact site involvement and BSA category using Mantel- Haenszel weights. bP values were calculated based on Cochran-Mantel-Haenszel chi-square test stratified by high-impact site involvement and BSA category, if applicable. cAmong patients with a baseline ss-IGA score, sPGA-G score, or hf-PGA score ≥3 dP values were based on Cochran-Mantel-Haenszel chi-square test stratified by geographic region and/or BSA category. eResults were not statistically significant f gAmong patients with a baseline PSSD Symptom score>0. hAmong patients with a baseline ss-IGA score ≥3 iP values were based on Cochran-Mantel-Haenszel chi-square test stratified by geographic region and BSA category jAmong patients with a baseline Scalp Itch NRS score ≥4 and a ss-IGA score ≥3. | ||
Safety
- Through week 16, 50% (104/208) of patients receiving icotrokinra and 42% (43/103) of patients receiving PBO reported ≥1 AE (see Table: Adverse Events through Week 16).1
- No new safety signals were identified through week 16.1
| Icotrokinra 200 mg QD (n=208) | Placebo (n=103) | |
|---|---|---|
| Mean weeks of follow-up | 16 | 15.7 |
| Any AE | 104 (50%) | 43 (42%) |
| Most common AEs (≥5%) | ||
| Nasopharyngitis | 26 (12%) | 11 (11%) |
| Upper respiratory tract infection | 9 (4%) | 5 (5%) |
| Headache | 6 (3%) | 6 (6%) |
| SAEa | 1 (<1%) | 2 (2%) |
| Infection | 59 (28%) | 22 (21%) |
| Serious Infection | 0 | 1 (1%) |
| AE leading to discontinuationb | 4 (2%) | 3 (3%) |
| Gastrointestinal AE | 15 (7%) | 8 (8%) |
| Active tuberculosis | 0 | 0 |
| Malignancyc | 1 (<1%) | 0 |
| Abbreviations: AE, adverse events; COVID-19, coronavirus disease 2019; QD, once daily; SAEs, serious adverse events aSAEs through week 16 included COVID-19 pneumonia, sepsis, sciatica, and acute respiratory failure in the placebo group; and hepatitis in the icotrokinra group. bAEs leading to discontinuation through W16 included COVID-19 pneumonia, psoriatic arthropathy, and psoriasis in the placebo group; and vision blurred, visual field defect, laryngitis fungal, malignant melanoma in situ, and headache in the icotrokinra group. cMalignancy reported in the icotrokinra group was malignant melanoma in situ in a patient with a recent personal history of melanoma (in 2021). | ||
Literature Search
A literature search of MEDLINE®
REFERENCES