Clinical trial NCT03463187: Multi-Dose Study of SHR-1314 in Subjects With Moderate-to-severe Plaque Psoriasis
Official title: A Multi-Center, Randomized, Double-blind, Placebo-controlled, Multi-Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of SHR-1314 With Expanded Dose Finding in Subjects With Moderate-to-severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Moderate-to-severe Chronic Plaque Psoriasis
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-13
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: PartA is a multiple dose escalating design in 3 sequential cohorts at 3 dose levels (80mg, 160mg, and 240mg) in plaque psoriasis subjects.

Part B is a multiple dose, parallel-group design consisting of 4 treatment arms and 1 placebo arm to assess the efficacy and safety of s.c. injections of SHR-1314 in plaque psoriasis subjects.
Primary purpose: TREATMENT

Brief summary: This is a multi-regional, randomized, double-blind, placebo-controlled, clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SHR-1314 in adults with moderate-to-severe plaque psoriasis.

Detailed description: This study is a multiple dose escalating design to evaluate the safety, PK, and pharmacodynamics (PD) of multiple subcutaneous injections of SHR-1314. There are two parts in this study. The safety, PK, and PD will be evaluated in Part A, the dose escalation part. The efficacy and safety on different doses will be assessed in parallel-groups in Part B.

Eligibility criteria: Major Inclusion Criteria:

1. Provide written informed consent before any study assessment is performed.
2. Male or female at least 18 years of age at screening.
3. At the time of randomization, moderate to severe plaque psoriasis, defined by:

   * PASI score of 12 or greater and
   * PGA score of 3 or greater and
   * BSA affected by plaque-type psoriasis of 10% or greater.
4. Subject is a candidate for systemic psoriasis therapy and/or phototherapy and/or chemo phototherapy.

Major Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic, and guttate psoriasis) at screening.
2. Drug-induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at randomization.
3. Active systemic infections (other than common cold) during the two weeks before randomization (e.g., hepatitis), or serious infections requiring hospitalization and/or intravenous injection of antibiotic treatment within eight weeks from randomization.
4. Presence of other skin conditions (e.g. skin infections, seborrheic dermatitis) that in the judgement of the Investigator could interfere with assessment of psoriasis.
5. History of inflammatory bowel disease or have other ongoing active autoimmune diseases.
6. At screening, history or symptoms of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
7. History of depression and/or suicidal ideation or behavior which in the opinion of the Investigator, makes the subject unsuitable for clinical study participation.
8. Any severe, progressive or uncontrolled medical condition at randomization that in the judgement of the Investigator prevents the subject from participating in the study.
9. Have a known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study.
10. Concurrent or recent use of psoriasis treatments/ medications.
11. Are currently enrolled in, or discontinued from a clinical trial involving an Investigational product (IP) within the last 4 weeks or at least 5 half-lives of the last dosing prior to randomization, whichever is longer; or concurrently enrolled (at randomization) in any other trials.
12. Have had a live attenuated vaccination within 12 weeks before randomization, or intend to have a live attenuated vaccination during the course of the study, or have participated in a vaccine clinical trial within 12 weeks prior to randomization.
13. Have evidence of positive test for hepatitis B, hepatitis C antibody, or human immunodeficiency virus (HIV) antibodies.

    A positive test for hepatitis B is defined as 1) positive for hepatitis B surface antigen \[HBsAg\], or 2) positive for anti-hepatitis B core antibody \[HBcAb+\] but negative for hepatitis B surface antibody \[HBsAb-\].
14. History or evidence of active or latent tuberculosis at screening.
15. Have laboratory test values that are considered clinically significant at screening that, in the opinion of the Investigator, pose an unacceptable risk to the subject if participating in the study or of interfering with the interpretation of data.
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test at screening or Day 0.
17. Females of child bearing potential (defined as all females physiologically capable of becoming pregnant) and males who are unwilling or unable to use highly effective contraception during the study and 20 weeks after the last administration of investigational product (anticipated 5 half-lives).
18. History of alcohol or illicit drug abuse within the year prior to screening.
19. Are unwilling or unable to maintain their normal pattern of alcohol, caffeine, smoking, and exercise from the start to the end of the study.
20. Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the Investigator.

Primary outcomes:
measure: Number of Participants With Clinically Significant Events (Part A)
timeFrame: From baseline through 24 weeks
measure: Pharmacokinetics (PK) of SHR-1314 (Part A)
timeFrame: From baseline through 24 weeks
measure: Pharmacokinetics (PK) of SHR-1314 (Part A)
timeFrame: From baseline through 24 weeks
measure: Percentage of Participants With Anti-SHR-1314 Antibodies (Part A)
timeFrame: From baseline through 24 weeks
measure: Percentage of subjects who achieve Psoriasis Area Severity Index (PASI) score 75 (Part B)
timeFrame: From baseline through 12 weeks
Secondary outcomes:
measure: Psoriasis Area Severity Index (PASI) score
timeFrame: From baseline through 24 weeks (Part A) or 36 weeks (Part B)
measure: Physician's Global Assessment (PGA) of 0 or 1 achievement
timeFrame: From baseline through 24 weeks (Part A) or 36 weeks (Part B)
measure: Change of dermatology life quality index (DLQI) score
timeFrame: From baseline up to 12 weeks (Part A) or 36 weeks (Part B)
measure: Change from baseline in Body Surface Area (BSA)
timeFrame: From baseline through 12 weeks (Part A) or (Part B)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Doral
country: United States
facility: Revival Research
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center - Emergency Medicine
state: Florida
city: Chicago
country: United States
facility: Great Lakes Clinical Trials LLC
state: Illinois
city: Johnston
country: United States
facility: Clinical Partners, LLC
state: Rhode Island
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Kogarah
country: Australia
facility: St George Dermatology and Skin Cancer Centre - Dermatology
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research Pty Ltd
state: Queensland
city: East Melbourne
country: Australia
facility: Sinclair Dermatology - Dermatology
state: Victoria
city: Shanghai
country: China
facility: Shanghai Huanshan Hospital Fudan University-Dermatology
Study officials:
References:
citation: Zhang C, Yan K, Diao Q, Guo Q, Jin H, Yang S, Chen X, Lei T, Wu J, Yu H, Zheng M, Gao X, Sinclair R, Zhu Y, Xu Q, Xu J. A multicenter, randomized, double-blinded, placebo-controlled, dose-ranging study evaluating the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2022 Jul;87(1):95-102. doi: 10.1016/j.jaad.2022.01.005. Epub 2022 Jan 10.