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icotrokinra

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Icotrokinra - Overview of the ICONIC-TOTAL Clinical Trial

Last Updated: 12/24/2025

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 5 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.1,2,7 
    • 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.1 
    • At week 52, IGA 0/1 was achieved by 67% of patients receiving icotrokinra and 68% of patients who transitioned from PBO to icotrokinra at week 16.7 
    • At week 52, ss-IGA 0/1, hf-PGA 0/1, and sPGA-G 0/1 was achieved by 72%, 62%, and 85% of patients receiving icotrokinra, respectively.7 
    • At week 52, ss-IGA 0/1, hf-PGA 0/1, and sPGA-G 0/1 was achieved by 71%, 68%, and 94% of patients who transitioned from PBO to icotrokinra at week 16, respectively.7 
    • Through week 16, 50% of patients receiving icotrokinra and 45% of patients receiving PBO reported ≥1 adverse event (AE).7
    • Through week 52, 74% of patients receiving icotrokinra and 68% of patients in the icotrokinra combined group reported ≥1 AE. No safety signals were identified for patients receiving icotrokinra.7

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 200 mg compared with 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/Exclusion Criteria for ICONIC-TOTAL1,2
Inclusion Criteria
Exclusion Criteria
  • Adults (≥18 years) and adolescents (≥12 to <18 years) with a diagnosis of plaque PsO for ≥26 weeks (with or without PsA) who were candidates for phototherapy or systemic therapy and failed ≥1 topical therapy
  • Total affected 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
  • 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)
  • Prior failure or intolerance to ≥1 biological agent targeting IL-23 (other than IL-12/23), or previously treated with icotrokinra
Abbreviations: BSA, body surface area; hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment; IL, interleukin; PsA, psoriatic arthritis; PsO, psoriasis; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment.
  • Adult and adolescent patients were randomized in a 2:1 ratio to receive icotrokinra 200 mg oral or PBO once daily with PBO crossover to icotrokinra at week 16. See Figure: ICONIC-TOTAL Study Design.

ICONIC-TOTAL Study Design8

Abbreviations: PBO, placebo; PE, primary endpoint; QD, once daily; R, randomization.


ICONIC-TOTAL Key Clinical Trial Outcome Measures at Week 161,2 
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
Abbreviations: hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment; NRS, numeric rating scale; PSSD, Psoriasis Symptom and Sign Diary; PSSI 90, Psoriasis Scalp Severity Index ≥90%; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment.
Note: Additional details regarding study outcome definitions can be found on clinicaltrials.gov.

Results

Patient Characteristics

Demographics and Baseline Clinical Characteristics8 
ICO
200 mg QD
(n=208)
PBO
(n=103)
Demographics
   Age, years, mean (SD)
45.3 (14.6)
43.5 (13.8)
   Male, n (%)
137 (65.9)
63 (61.2)
   Race, (%)
      Asian /Black /White /Other-NR
19.7/1.0/77.4/1.9
19.4/0/79.6/1.0
   BMI, kg/m2, mean (SD)
(n=203)
29.0 (6.6)
(n=101)
29.4 (8.1)
Disease characteristics
   Duration of PsO, years, mean (SD)
16.8 (13.3)
15.2 (10.5)
   PASI total score, mean (SD)
14.6 (7.6)
14.0 (7.0)
   % BSA with PsO, mean (SD)
16.6 (13.5)
14.8 (11.7)
      <10%, n (%)
74 (35.6)
38 (36.9)
      ≥10%, n (%)
134 (64.4)
65 (63.1)
   Overall IGA score, n (%)
      3, moderate plaque PsO
153 (73.6)
73 (70.9)
      4, severe plaque PsO
46 (22.1)
22 (21.4)
   ss-IGA score ≥3, n (%)a
167 (80.3)
85 (82.5)
      3, moderate scalp PsO
134/167 (80.2)
64/85 (75.3)
      4, severe scalp PsO
33/167 (19.8)
21/85 (24.7)
   sPGA-G score ≥3, n (%)a
98 (47.1)
42 (40.8)
      3, moderate genital PsO
75/98 (76.5)
29/42 (69.0)
      4, severe genital PsO
22/98 (22.4)
12/42 (28.6)
   hf-PGA score ≥3, n (%)a
48 (23.1)
23 (22.3)
    3, moderate hand/foot PsO
31/48 (64.6)
19/23 (82.6)
    4, severe hand/foot PsO
17/48 (35.4)
4/23 (17.4)
   PSSD Symptom score, mean (SD)
(n=191)
53.2 (26.3)
(n=87)
54.6 (26.4)
      PSSD Itch score
6.4 (2.3)
6.5 (2.5)
   PSSD Sign score, mean (SD)
(n=191)
57.3 (22.4)
(n=87)
58.2 (21.7)
Previous therapy, n (%)
   Any PsO systemic therapyb
151 (72.6)
75 (72.8)
      Conventional nonbiologic therapyc
103 (49.5)
55 (53.4)
      Phototherapy
89 (42.8)
32 (31.1)
      Biologic therapyd
71 (34.1)
32 (31.1)
      Oral nonbiologic systemic therapye
15 (7.2)
7 (6.8)
      1,25-vitamin D3 and its analogs
7 (3.4)
6 (5.8)
Abbreviations: BMI, body mass index; BSA, body surface area; hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; IGA, Investigator’s Global Assessment; IL, interleukin; NR, not reported; PASI, Psoriasis Area and Severity Index; PBO, placebo; PsO, psoriasis; PSSD, Psoriasis Symptom and Sign Diary; QD, once daily; SD, standard deviation; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment.
aPsO involving high-impact sites was not mutually exclusive.
bIncludes conventional nonbiologic systemic therapies, phototherapy, biologics, oral nonbiologic systemic therapies, and 1,25-vitamin D3 and its analogs.
cIncludes acitretin, azathioprine, cyclosporine, fumarate, methotrexate, and psoralen plus ultraviolet A.
dIncludes adalimumab, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, etanercept, guselkumab, infliximab, ixekizumab, natalizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab.
eIncludes apremilast, deucravacitinib, and tofacitinib.
Efficacy- Week 16

Key Clinical Endpoints at Week 161
ICO
200 mg QD
(n=208)
PBO
(n=103)
Treatment Difference, % (95% CI); Adjusted P-Valuea
Proportion of patients achieving endpoint, n (%)
   IGA 0/1- Primary endpoint
118 (56.7)
6 (5.8)
51.1 (42.1-58.8); P<0.001
   ss-IGA 0/1b
110 (65.9)
9 (10.6)
55.5 (44.8-64.4); P<0.001
   sPGA-G 0/1c
75 (76.5)
9 (21.4)
55.4 (39.1-68.0); P<0.001
   hf-PGA 0/1d
20 (41.7)
6 (26.1)
16.7 (-6.2 to 36.8); P=0.14
   IGA 0
53 (25.5)
1 (1.0)
24.8 (17.4-31.5); P<0.001
   ≥4-point improvement in PSSD Itch score
   from baselinee
100 (59.5)
10 (13.5)
45.2 (33.4-55.3); P<0.001
   PSSD Symptom score of 0f
31 (16.2)
3 (3.4)
12.8 (5.5-19.4); P=0.008
   ≥90% improvement in PSSI score from
   baseline
96 (57.5)
5 (5.9)
51.8 (41.7-60.3); P=0.008
   Scalp Itch NRS score improvement of ≥4
   points from baselineg
77 (58.8)
5 (8.6)
50.2 (37.8-60.6); P=0.008
Abbreviations: CI, confidence interval; hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; IGA, Investigator’s Global Assessment; NRS, numeric rating scale; PBO, placebo; PSSD, Psoriasis Symptom and Sign Diary (symptom score range, 0-100); PSSI, Psoriasis Scalp Severity Index; QD, once daily; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment.
aP-values for key secondary endpoints were adjusted for multiplicity.
bFor ss-IGA, only participants with baseline scores ≥3 were included (PBO, n=85; icotrokinra, n=167).
cFor sPGA-G, only participants with baseline scores ≥3 were included (PBO, n=42; icotrokinra, n=98).
dFor hf-PGA, only participants with baseline scores ≥3 were included (PBO, n=23; icotrokinra, n=48).
eOnly participants with a baseline PSSD Itch score of ≥4 were included (PBO, n=74; icotrokinra, n=168).
fOnly participants with a baseline PSSD Symptom score of >0 were included (PBO, n=87; icotrokinra, n=191).
gOnly participants with a baseline Scalp Itch NRS score of ≥4 and ss-IGA score of ≥3 were included (PBO, n=58; icotrokinra, n=131).
  • The proportion of patients who achieved a ≥4-point improvement in the Genital Psoriasis Symptoms Scale (GPSS) in Genital Itch Numeric Rating Scale (NRS) was 63.8% and 12.9% in the icotrokinra and PBO groups, respectively (treatment difference, 49.8; 95% CI, 31.3-64.3; P=0.008).
    • Only participants with a baseline GPSS Genital Itch NRS score of ≥4 and sPGA-G score of ≥3 were included (PBO, n=31; icotrokinra, n=69).
  • The proportion of patients who achieved a Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ) Item 2 score of 0/1 was 80.0% and 36.0% in the icotrokinra and PBO groups, respectively (treatment difference, 43.2; 95% CI, 20.2-62.4; P=0.008).
    • Only participants with a baseline GenPs-SFQ Item 2 score of ≥2 and sPGA-G score of ≥3 were included (PBO, n=25; icotrokinra, n=55).1 

Lain et al (2025)7 reported results through week 52 from ICONIC-TOTAL, a phase 3 clinical trial evaluating the efficacy and safety of icotrokinra compared with PBO for the treatment of adults and adolescents (≥12 years of age) with plaque PsO and high-impact site involvement.

Study Design/Methods

Results

Efficacy- Week 52

Key Clinical Outcomes at Week 527 
ICO
200 mg QD
PBO→ICOa
Proportion of patients achieving endpoint, %
n=208
n=92
   IGA 0/1 and ≥2-grade improvement from baseline
67
68
   IGA 0
45
44
n=167
n=75
   ss-IGA 0/1b
72
71
   ss-IGA 0b
57
61
n=98
n=36
   sPGA-G 0/1c
85
94
   sPGA-G 0c
73
86
n=48
n=19
   hf-PGA 0/1d
62
68
   hf-PGA 0d
58
58
   mNAPSIc, mean improvement from baseline, %(n)
62 (78-81)
59 (46)
Abbreviations: hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; IGA, Investigator’s Global Assessment; mNAPSI, modified Nail Psoriasis Severity Index; PBO, placebo; QD, once daily; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment.
aIncludes PBO-randomized patients who transitioned to ICO at week 16.
bAmong patients with a baseline ss-IGA score of ≥3.
cAmong patients with a baseline sPGA-G score of ≥3.
dAmong patients with a baseline hf-PGA score of ≥3.
eAmong patients with a baseline mNAPSI score of >0.
Safety
  • Through week 16, 50% (105/208) of patients receiving icotrokinra and 45% (46/103) of patients receiving PBO reported ≥1 AE.7
  • Through week 52, 74% (153/208) of patients receiving icotrokinra and 68% (204/300) of patients in the icotrokinra combined group reported ≥1 AE (See Table: AEs through Week 52).
  • No safety signals were identified through week 52.7 

AEs through Week 527
Weeks 0-16
Weeks 16-52
Through Week 52
ICO (n=208)
PBO (n=103)
PBO→ICO (n=92)
ICO
(n=208)
ICO Combineda (n=300)
Mean weeks/total PY of follow-up
16.0/63.6
15.6/30.8
36.2/63.9
49.3/196.4
45.3/260.2
Any AE, n (%)
105 (50)
46 (45)
51 (55)
153 (74)
204 (68)
SAEs, n (%)
1 (<1)
2 (2)
1 (1)
6 (3)
7 (2)
AEs leading to discontinuation, n (%)
6 (3)
4 (4)
0
7 (3)
7 (2)
Infections, n (%)
59 (28)
23 (22)
39 (42)
106 (51)
145 (48)
Serious infections, n (%)
0
1 (1)
0
0
0
Gastrointestinal AEs, n (%)
15 (7)
8 (8)
7 (8)
21 (10)
28 (9)
Malignancyb
1 (<1)
0
0
2 (1)
2 (1)
Abbreviations: AE, adverse event; ICO, icotrokinra; PBO, placebo; SAE, serious adverse event; PY, patient-years.
aIncludes data for ICO-randomized patients through week 52 and for PBO-to-ICO patients from week 16 through week 52.
bMalignancy includes chronic lymphocytic leukemia and malignant melanoma in situ.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 03 December 2025.

References

Show
1 Gooderham M, Lain E, Bissonnette R, et al. Targeted oral peptide icotrokinra for psoriasis involving high-impact sites. [published online ahead of print November 5, 2025]. NEJM Evid. doi:10.1056/evidoa2500155.  
2 Janssen Research & Development, LLC. A study of JNJ-77242113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/​or palms of the hands and the soles of the feet) (ICONIC-TOTAL). ln: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06095102 NLM Identifier: NCT06095102.  
3 Janssen Research & Development, LLC. A study of JNJ-77242113 for the treatment of participants with moderate to severe plaque psoriasis. ln: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06143878 NLM Identifier: NCT06143878.  
4 Janssen Research & Development, LLC. A study of JNJ-77242113 in adolescent and adult participants with moderate to severe plaque psoriasis (ICONIC-LEAD). ln: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06095115 NLM Identifier: NCT06095115.  
5 Janssen Research & Development, LLC. A study of JNJ-77242113 for the treatment of participants with moderate to severe plaque psoriasis (ICONIC-ADVANCE 2). ln: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06220604 NLM Identifier: NCT06220604.  
6 Janssen Research & Development, LLC. A study to assess efficacy and safety of JNJ-77242113 compared to placebo and ustekinumab in participants with moderate to severe plaque psoriasis (ICONIC-ASCEND). ln: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06934226 NLM Identifier: NCT06934226.  
7 Lain E, Warren RB, Gooderham M, et al. Durability of response to the targeted oral peptide icotrokinra for high-impact site psoriasis: 1-year ICONIC-TOTAL findings. Poster presented at: Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.  
8 Gooderham M, Lain E, Bissonnette R, et al. Supplement to: Targeted oral peptide icotrokinra for psoriasis involving high-impact sites. [published online ahead of print November 5, 2025]. NEJM Evid. doi:10.1056/evidoa2500155.