A Randomized, Double-blinded, and Placebo-controlled Phase I/II Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis
Overview
- Phase
- Phase 1
- Intervention
- AK101
- Conditions
- Plaque Psoriasis
- Sponsor
- Akeso
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Incidence of treatment emergent adverse events (TEAEs)
- Status
- Completed
- Last Updated
- last year
Overview
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)..
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have had Plaque Psoriasis diagnosed at least 6 months prior to screening.
- •Clinical diagnosis of stable plaque psoriasis with involvement of ≥ 10% body surface area. Psoriasis area and severity index(PASI) ≥
- •Physicians Global Assessment score ≥
- •Patients who have received systemic therapy or phototherapy, or who have been allowed by the investigator to receive systemic therapy or phototherapy.
- •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.
- •Ability to provide written informed consent and to be compliant with the schedule of protocol assessments.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.
Exclusion Criteria
- •Had nonplaque forms of psoriasis (e.g., Guttate, erythrodermic, or pustular).
- •Had other active skin diseases or skin infections (e.g., bacterial, fungal or viral infection) that could affect psoriasis evaluation.
- •Had Imaging diagnosis of pulmonary infection or fibrosis during the 3 months prior to screening.
- •History or evidence of active or latent tuberculosis at screening.
- •Serious systemic infections or local infections during the 2 months prior to screening.
- •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).
- •Known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study.
- •History of alcohol or drug abuse.
- •History or known presence of recurrent or chronic infection (e.g., hepatitis B, or C, human immunodeficiency virus \[HIV\], syphilis, TB).
- •Had received any DMARDs (e.g., anti-malaria drug, retinoids, interferon, lithium) during 2 weeks prior to screening.
Arms & Interventions
Phase I: AK101 45 mg
Biological: AK101 AK101 45 mg on Week 0 and 4 by subcutaneous injection
Intervention: AK101
Phase I: AK101 135 mg
Biological: AK101 AK101 135 mg on Week 0 and 4 by subcutaneous injection
Intervention: AK101
Phase I: AK101 270 mg
Biological: AK101 AK101 270 mg on Week 0 and 4 by subcutaneous injection
Intervention: AK101
Phase I: Placebo
Biological: Placebo Placebo on Week 0 and 4 by subcutaneous injection
Intervention: placebo
Phase II: AK101 45 mg
Biological: AK101 AK101 45 mg on Week 0, 4 and 16 by subcutaneous injection
Intervention: AK101
Phase II: AK101 90 mg
Biological: AK101 AK101 90 mg on Week 0, 4 and 16 by subcutaneous injection
Intervention: AK101
Phase II: AK101 135 mg
Biological: AK101 AK101 135 mg on Week 0, 4 and 16 by subcutaneous injection
Intervention: AK101
Phase II: Placebo to AK101
Drug: Placebo Placebo on Week 1 and 4 by subcutaneous injection, and then AK101 on Week 12 16 by subcutaneous injection
Intervention: AK101
Phase II: Placebo to AK101
Drug: Placebo Placebo on Week 1 and 4 by subcutaneous injection, and then AK101 on Week 12 16 by subcutaneous injection
Intervention: placebo
Outcomes
Primary Outcomes
Incidence of treatment emergent adverse events (TEAEs)
Time Frame: From the time of signing informed consent till Week 16 for Phase I or Week 28 for Phase II
Secondary Outcomes
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose till Week 16 for Phase I or Week 28 for Phase II)
- Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Minimum observed concentration (Cmin) of AK101(From first dose till Week 16 for Phase I or Week 28 for Phase II)
- Number of participants who achieved ≥ 90% reduction in PASI (PASI90)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Area under the curve (AUC) of AK101(From first dose till Week 16 for Phase I)
- Change From Baseline in the Physician Global Assessment (PGA)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Maximum observed concentration (Cmax) of AK101(From first dose till Week 16 for Phase I or Week 28 for Phase II)