Clinical trial NCT04172233: A Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis
Official title: A Randomized, Double-blinded, and Placebo-controlled Phase I/II Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Plaque Psoriasis
Keywords: IL12/23
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: Akeso Tiancheng, Inc
First posted: 2019-11-21
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and the preliminary efficacy of AK101，an anti-IL-12/23p40 monoclonal antibody, when administered subcutaneously in subjects with moderate-to-severe plaque psoriasis.

Detailed description: This was a single-center, randomized, double-blind, placebo-controlled trial which consisted of a dose escalation phase (Phase I) and a dose expansion phase (Phase II)..

Eligibility criteria: Inclusion Criteria:

1. Have had Plaque Psoriasis diagnosed at least 6 months prior to screening.
2. Clinical diagnosis of stable plaque psoriasis with involvement of ≥ 10% body surface area. Psoriasis area and severity index(PASI) ≥12. Physicians Global Assessment score ≥3.
3. Patients who have received systemic therapy or phototherapy, or who have been allowed by the investigator to receive systemic therapy or phototherapy.
4. Women of childbearing potential should not be in pregnancy or lactation, men and women of childbearing potential must agree to use adequate birth control measures during study participation and for 6 months after the last dose of study treatment.
5. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.

Exclusion Criteria:

1. Had nonplaque forms of psoriasis (e.g., Guttate, erythrodermic, or pustular).
2. Had other active skin diseases or skin infections (e.g., bacterial, fungal or viral infection) that could affect psoriasis evaluation.
3. Had Imaging diagnosis of pulmonary infection or fibrosis during the 3 months prior to screening.
4. History or evidence of active or latent tuberculosis at screening.
5. Serious systemic infections or local infections during the 2 months prior to screening.
6. History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved).
7. Known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study.
8. History of alcohol or drug abuse.
9. History or known presence of recurrent or chronic infection (e.g., hepatitis B, or C, human immunodeficiency virus \[HIV\], syphilis, TB).
10. Had received any DMARDs (e.g., anti-malaria drug, retinoids, interferon, lithium) during 2 weeks prior to screening.
11. Had received any physical therapy (e.g., PUVA, ultra-violet therapy, tanning beds) during 2 weeks prior to screening.
12. Had received any systemic psoriasis therapy (e.g., glucocorticoid, retinoids, ciclosporin, methotrexate, or tripterygium) during 4 weeks prior to screening.
13. Had Enrolled in any other trials during 3 months prior to screening or concurrently enrolled in any other trials.
14. Had received previous treatment with any anti-IL-12/IL-23, IL-12, IL-23, IL-17 therapy for the treatment of psoriasis or psoriatic arthritis.
15. Had received previous treatment with natalizumab or any other drugs that regulate B cells or T cells (rituximab, abatacept, alemtuzumab) during 12 months prior to screening.
16. Had received other biologic therapy (e.g., TNF inhibitor) during 6 months prior to screening.

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: From the time of signing informed consent till Week 16 for Phase I or Week 28 for Phase II
Secondary outcomes:
measure: Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75)
timeFrame: At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II)
measure: Number of participants who achieved ≥ 90% reduction in PASI (PASI90)
timeFrame: At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II)
measure: Change From Baseline in the Physician Global Assessment (PGA)
timeFrame: At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II)
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose till Week 16 for Phase I or Week 28 for Phase II
measure: Area under the curve (AUC) of AK101
timeFrame: From first dose till Week 16 for Phase I
measure: Minimum observed concentration (Cmin) of AK101
timeFrame: From first dose till Week 16 for Phase I or Week 28 for Phase II
measure: Maximum observed concentration (Cmax) of AK101
timeFrame: From first dose till Week 16 for Phase I or Week 28 for Phase II
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Rui Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking Union Medical College Hospital
name: Hongzhong Jin, MD
role: PRINCIPAL_INVESTIGATOR
References: