Clinical trial NCT02649270: Tolerability, Safety and Pharmacokinetic Study of Humanized Anti-CD6 Monoclonal Antibody Injection in Chinese Psoriasis
Official title: Single and Multiple Dose -Based Tolerability, Safety and Pharmacokinetic Phase 1 Study of Humanized Anti-CD6 Monoclonal Antibody Injection in Chinese Patients With Psoriasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Psoriasis
Keywords: Tolerability
Safety
Pharmacokinetic Study
preliminary pharmacodynamic study
Humanized Anti-CD6 Monoclonal Antibody(T1h)
Lead sponsor: Biotech Pharmaceutical Co., Ltd.
Sponsor class: OTHER
First posted: 2016-01-07
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ranged from 18 to 55 years, males or females ( no less than 3 patients in each dose group)
2. Patients with chronic plaque psoriasis for at least 6 months (until patients with an informed consent) with or without arthritis psoriasis
3. BSA≥3% or PASI≥10
4. PGA≥3
5. 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
6. Fertile males or females who are willing to adopt contraceptive methods (e.g. hormonal pitch, intrauterine device, condoms)
7. Patients were voluntary to sign a written informed consent.

Exclusion Criteria:

1. The females were pregnant, or lactating or showed positive urine pregnancy reaction during screening.
2. Patients with erythroderma or pustular psoriasis.
3. Patients receiving glucocorticoid systemic drug therapy.
4. 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
5. Patients with any active infection (nail bed induced fungal infections were excluded), chronic infections, and tuberculosis history.
6. Patients with severe heart disease, heart failure, asthma, chronic obstructive pulmonary disease or neuropsychiatric diseases.
7. Patients previously or currently suffered from tumors including solid tumors, hematologic malignancies and carcinoma in situ.
8. Patients with positive tests for hepatitis B surface antigen (HBsAg), hepatitis C serology (HCV-Ab) or human immunodeficiency virus (HIV-Ab)
9. 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
10. 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.
11. Patients with a history of drug abuse or alcoholism
12. Patients were allergic to a recombinant biologic agent or any component of proteins derived from murine
13. Patients with surgery within three months or any planned surgery or laser skin treatment within six months
14. Patients received any vaccination within 28 days
15. Patients received any experimental drug treatment within three months
16. Patients were not suitable determined by researchers

Primary outcomes:
measure: Adverse events
timeFrame: from patients with informed consents to 30 days after the last administration
Secondary outcomes:
measure: single-dose ,Peak plasma concentration (Cmax) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose, Area under the plasma concentration versus time curve( AUC(0-t)) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose, Area under the plasma concentration versus time curve(AUC(0-∞))of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose, Time to peak(Tmax) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose,Elimination rate constant （kel）of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose,Half time (t1/2) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose,Total body clearance (CLs)of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose,Apparent volume of distribution(Vd) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: single-dose,Mean residence time(MRT) of T1h
timeFrame: -2h、-1h、-0.5h、0h、1h、2h、6h、12h、24h、2d、3d、7d、14d、21d、28d after administration
measure: multiple dose,Time to peak(Tmax) of T1h
timeFrame: -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
measure: multiple dose,Peak plasma concentration in steady state(Css_max) of T1h
timeFrame: -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
measure: multiple dose,Minimum plasma concentration in steady state(Css_min) of T1h
timeFrame: -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
measure: multiple dose,Average plasma concentration in steady state(Css_avg) of T1h
timeFrame: -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
measure: multiple dose, Area under the plasma concentration versus time curve in steady state(AUCss) of T1h
timeFrame: -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
measure: multiple dose,Apparent volume of distribution in steady state (Vss) of T1h
timeFrame: -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
measure: multiple dose,Degree of fluctuation (DF) of T1h
timeFrame: -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
measure: multiple dose,Accumulation Index(AI) of T1h
timeFrame: -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
measure: Erythrocyte sedimentation rate(ESR)
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: C-reactive protein(CRP)
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: Tumor Necrosis Factor -alpha(TNF-α)
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: Interleukin (il)-6 (IL-6)
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: interferon--γ (IFN-γ)
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: CD6
timeFrame: week7,9 at -2h;week13 at -2h,24h,7d,14d,21d,28d after administration
measure: Psoriasis Area and Severity Index(PASI)
timeFrame: at the end of 4th week,8th week,12th week after administration
measure: Physician's Global Assessment(PGA)
timeFrame: The 29th day,The 57th day,The 85th day and The 113th day after administration
measure: Body surface area(BSA)
timeFrame: The 29th day,The 57th day,The 85th day and The 113th day after administration
Other outcomes:
Locations:
city: BeiJing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
Study officials:
affiliation: Beijing Chao Yang Hospital
name: lihong liu
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chao Yang Hospital
name: yanling he
role: PRINCIPAL_INVESTIGATOR
References: