Tolerability, Safety and Pharmacokinetic Study of Humanized Anti-CD6 Monoclonal Antibody Injection in Chinese Psoriasis

Study Overview
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Brief Summary
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The humanized recombinant anti-CD6 monoclonal antibody Injection (T1h) has been approved for psoriasis in India. The first trial in China is to evaluate the tolerability, safety, pharmacodynamic, pharmacokinetics and preliminary efficacy of T1h for patients with psoriasis.

Detailed Description
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The humanized recombinant anti-CD6 monoclonal antibody (T1h) is developed whose ligand binding properties of the original murine monoclonal antibody are preserved on the CD6 molecule. T1h monoclonal antibody has been approved for clinical studies of autoimmune diseases in Cuba and India, such as psoriasis and rheumatoid arthritis (RA). Single and multiple dose based tolerability, safety and pharmacokinetic phase 1 Study of Humanized Anti-CD6 Monoclonal Antibody Injection in Chinese patients with psoriasis, 40 patients are enrolled. They are divided into 4 groups (0.2mg/kg, 0.4mg/kg, 0.8mg/kg, 1.6mg/kg) and each group includes 10 patients. First, these doses are all single-dose administration gradually from low then the doses 0.4mg/kg, 0.8mg/kg and 1.6mg/kg are multi-dose administration gradually from low.

Official Title
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Single and Multiple Dose -Based Tolerability, Safety and Pharmacokinetic Phase 1 Study of Humanized Anti-CD6 Monoclonal Antibody Injection in Chinese Patients With Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: T1h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ranged from 18 to 55 years, males or females ( no less than 3 patients in each dose group) Patients with chronic plaque psoriasis for at least 6 months (until patients with an informed consent) with or without arthritis psoriasis BSA≥3% or PASI≥10 PGA≥3 Patients were eligible if wash-out period was no less than the time as follows: 2 weeks for topical retinoic acid or glucocorticoid therapy 6 months for retinoic acid of this kind drugs therapy 2 weeks for light therapy 4 weeks for Psoralen combined with UV-A therapy 4 weeks for methotrexate(MTX),cyclophosphamide,cyclosporine and other immunosuppressive therapy 7 half life time periods for other systemic immunosuppressive therapy 8 weeks for Biological agents for psoriasis therapy Fertile males or females who are willing to adopt contraceptive methods (e.g. hormonal pitch, intrauterine device, condoms) Patients were voluntary to sign a written informed consent. Exclusion Criteria: The females were pregnant, or lactating or showed positive urine pregnancy reaction during screening. Patients with erythroderma or pustular psoriasis. Patients receiving glucocorticoid systemic drug therapy. Patients previously or currently suffered from autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome ), or suffering from primary or secondary immunodeficiency or human immunodeficiency virus Patients with any active infection (nail bed induced fungal infections were excluded), chronic infections, and tuberculosis history. Patients with severe heart disease, heart failure, asthma, chronic obstructive pulmonary disease or neuropsychiatric diseases. Patients previously or currently suffered from tumors including solid tumors, hematologic malignancies and carcinoma in situ. Patients with positive tests for hepatitis B surface antigen (HBsAg), hepatitis C serology (HCV-Ab) or human immunodeficiency virus (HIV-Ab) Patients with Hemoglobin < 90 g/L, white blood cell count <3.5 × 10^9 / L, neutrophil count <1.5 × 10^9 / L, or platelet count <80 × 10^9 / L Patients with more than doubled serum cereal third transaminase(ALT )and glutamic-oxaloacetic transaminase(AST) as the upper limit of the reference value or serum creatinine values were above the upper limit of the reference. Patients with a history of drug abuse or alcoholism Patients were allergic to a recombinant biologic agent or any component of proteins derived from murine Patients with surgery within three months or any planned surgery or laser skin treatment within six months Patients received any vaccination within 28 days Patients received any experimental drug treatment within three months Patients were not suitable determined by researchers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group1<br>10 Psoriasis patients,T1h 0.2mg/kg,only single dose administration at week 1. | Biological: T1h<br>* Given T1h for different groups by vein to evaluate safety and tolerability;Collecting blood samples for pharmacokinetics and pharmacodynamics after administration.<br>* Other names: Anti-CD6 Monoclonal Antibody;|
| Experimental: Group2<br>10 Psoriasis patients,T1h 0.4mg/kg ,first administration at week 1 and continous administration from fifth week for 9 weeks. | Biological: T1h<br>* Given T1h for different groups by vein to evaluate safety and tolerability;Collecting blood samples for pharmacokinetics and pharmacodynamics after administration.<br>* Other names: Anti-CD6 Monoclonal Antibody;|
| Experimental: Group3<br>10 Psoriasis patients,T1h 0.8mg/kg,first administration at week 1 and continous administration from fifth week for 9 weeks. | Biological: T1h<br>* Given T1h for different groups by vein to evaluate safety and tolerability;Collecting blood samples for pharmacokinetics and pharmacodynamics after administration.<br>* Other names: Anti-CD6 Monoclonal Antibody;|
| Experimental: Group4<br>10 Psoriasis patients,T1h 1.6mg/kg,first administration at week 1 and biweekly from fifth week for 9 weeks. . | Biological: T1h<br>* Given T1h for different groups by vein to evaluate safety and tolerability;Collecting blood samples for pharmacokinetics and pharmacodynamics after administration.<br>* Other names: Anti-CD6 Monoclonal Antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | from patients with informed consents to 30 days after the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| single-dose ,Peak plasma concentration (Cmax) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose, Area under the plasma concentration versus time curve( AUC(0-t)) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose, Area under the plasma concentration versus time curve(AUC(0-∞))of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose, Time to peak(Tmax) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose,Elimination rate constant （kel）of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose,Half time (t1/2) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose,Total body clearance (CLs)of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose,Apparent volume of distribution(Vd) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| single-dose,Mean residence time(MRT) of T1h |  | -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration | 
| multiple dose,Time to peak(Tmax) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Peak plasma concentration in steady state(Css_max) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Minimum plasma concentration in steady state(Css_min) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Average plasma concentration in steady state(Css_avg) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose, Area under the plasma concentration versus time curve in steady state(AUCss) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Apparent volume of distribution in steady state (Vss) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Degree of fluctuation (DF) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| multiple dose,Accumulation Index(AI) of T1h |  | -2h,0h at week5,6,7,8,9,10,11,12;2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after week13 | 
| Erythrocyte sedimentation rate(ESR) |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| C-reactive protein(CRP) |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| Tumor Necrosis Factor -alpha(TNF-α) |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| Interleukin (il)-6 (IL-6) |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| interferon--γ (IFN-γ) |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| CD6 |  | week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration | 
| Psoriasis Area and Severity Index(PASI) |  | at the end of 4th week,8th week,12th week after administration | 
| Physician's Global Assessment(PGA) |  | The 29th day,The 57th day,The 85th day and The 113th day after administration | 
| Body surface area(BSA) |  | The 29th day,The 57th day,The 85th day and The 113th day after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, Safety, Pharmacokinetic Study, preliminary pharmacodynamic study, Humanized Anti-CD6 Monoclonal Antibody(T1h)