Rheumatoid arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: CDP6038
Product Code: CDP6038
Pharmaceutical Form: Solution for injection
CAS Number: 1007223-17-7
Current Sponsor code: CDP6038
Other descriptive name: recombinant human Mab of IgG4 sub
Sponsors
UCB Celltech
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has been informed and given ample time and opportunity to ask questions and to decide whether or not to participate and has provided written informed consent. The subject should also be able to communicate satisfactorily with the Investigator to participate in the study and to comply with all study requirements. 2. Subject is aged between 18 and 75 years (inclusive). 3. Subject has a diagnosis of RA (diagnosed according to ACR criteria) of more than 6 months’ duration and has been on a stable MTX dose of 5 to 25mg/week for at least 3 months prior to Screening. 4. Subject has =9 swollen and =9 tender joints (28-joint count) or a DAS28(CRP) of =5.10. 5. Subject has a minimum Screening CRP of 0.05mg/dL. 6. Confirmation that female subjects of child-bearing potential (ie, not surgically sterile by hysterectomy/bilateral oophorectomy or bilateral tubal ligation or postmenopausal for at least 2 years prior to Screening), use a contraceptive method over the entire exposure period and that a male partner use barrier contraception (eg, a condom). Abstinence is not considered an acceptable method of contraception. 7. Confirmation that the male subject, when having sexual intercourse with women of childbearing potential (ie, not surgically sterilized and not at least 2 years postmenopausal), will use a contraceptive barrier (eg, condom) over the entire exposure period and that the respective partner will use an additional contraceptive method. Abstinence is not considered an acceptable method of contraception. 8. Subject has a body mass index (BMI) between 19.0 and 38.0kg/m² (inclusive). 9. Subject has an ECG with interpretations considered as “normal” or as “abnormal” but within the agreed upon clinically nonsignificant ranges predefined by the Sponsor in the ECG manual. 10. Subject has results of clinical safety laboratory tests, including liver function tests, within the laboratory reference ranges or outside the laboratory reference range but within limits predefined by the Sponsor in the laboratory manual and deemed acceptable and not clinically relevant by the Investigator. 11. The subject is considered to be reliable and capable of adhering to the protocol, according to the judgment of the Investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Participation in any other clinical drug or device study (including a biologic product) as per protocol. 2. Subjects who have received prior treatment with: a) etanercept or anakinra within 4 weeks prior to screening, b) golimumab, infliximab, adalimumab, certolizumab pegol or abatacept within 3 months prior to screening, c) B-cell depleting therapy within 6 months prior to screening or B-cell depleting therapy =6 months prior to screening but who have CD19 counts =75 (cells/µL), d) any other experimental biologics within 3 months or 5 half-lives, which ever is longer, prior to screening, and e) tocilizumab or other anti-IL-6 preparations. 3. Subject is not willing to abstain from participating in any other study until the last study visit. 4. Presence of any medical condition (except for RA disease), including any form of primary immunodeficiency, leading to a deficiency in either adaptive or innate immune response. 5. Subject has a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, dermatological, neurological, psychiatric, hematological or immunologic disorder(s) which are clinically significant enough in the opinion of the Investigator to alter the absorption and disposition of drugs, or constitute a risk factor when taking the study medication. 6. Subject taking any medication for management of their RA disease, apart from MTX and those stated in Section 7.8.1. 7. Subject with a present condition of malignancy or history of malignancy as per protocol. 8. Subject with a history of prosthetic joint infection with the same prosthesis still in situ. 9. Subject with a known clinically relevant allergy or known severe adverse reaction to any drug, hypersensitivity to protein made from bacterial yeast or mammalian producer cells, or known or suspected clinically relevant drug hypersensitivity. 10. Female subjects who are pregnant or lactating. 11. Subject with a known, clinically significant history of any chronic latent, persistent, opportunistic, or severe bacterial, viral, systemic fungal, or parasitic infection within the 2 years prior to Screening, or any clinically significant recent (within the last 6 months prior to Screening) bacterial, viral, systemic fungal, parasitic infection, or any current sign or symptom that may indicate an infection. 12. Subjects with infections requiring more than 2 courses of antibiotics within the last 6 months prior to Screening. 13. Subject with a positive TIGRA (T-cell interferon-? release assay) and/or positive skin test (purified protein derivative [PPD] or positive TIGRA only, in case of contraindication to PPD skin testing, for tuberculosis and/or a chest x–ray showing evidence of possible latent/active tuberculosis. 14. Subject with evidence from chest x-ray of interstitial lung disease. Subjects with other abnormalities on chest x-ray which, in the opinion of the Investigator would prevent appropriate evaluation of the subject. 15. Subject with a positive test to Human Immunodeficiency Virus-1/2 antibody (HIV 1/2Ab). 16. Subject has known viral hepatitis, has a positive test for Hepatitis B surface antigen or is Hepatitis C virus antibody positive. 17. Subject with a history of chronic alcohol abuse within the last 2 years, or a positive alcohol test at Screening and/or Day-1. Subjects should restrict their alcohol consumption to no more than 1 unit per week. 18. Subject with a history of drug addiction within the last 2 year
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To characterize the PK/PD relationship between systemic CDP6038 exposure and CRP suppression, following single dose CDP6038 administration via iv infusion and sc injection to subjects with RA. • To evaluate the safety and tolerability of single doses of CDP6038 in RA subjects over a therapeutic dose range (as defined by CRP suppression).;Secondary Objective: • To determine the absolute bioavailability of CDP6038 given via sc administration in comparison with iv infusion in subjects with RA. • To assess the immunogenicity of single dose CDP6038 in subjects with RA. • To assess, on an exploratory basis, changes in clinical response and other systemic biomarkers with CDP6038 dosing.;Primary end point(s): • Pharmacodynamic variable: serum concentration of CRP by using a hsCRP assay. • Pharmacokinetic variables: Cmax, CL, Vd, AUC0-inf, tmax, and t1/2 of CDP6038 in plasma. Anti-CDP6038 antibodies will also be measured. • Exploratory systemic biomarkers: 1. Exploratory biomarkers of 1.1. bone turnover: bone degradation - serum carboxy-terminal crosslinked telopeptide of type I collagen (CTX-I) and bone synthesis - amino-terminal propeptide of type I procollagen (PINP) 1.2. cartilage turnover: cartilage synthesis - serum amino-terminal propeptide of type IIA procollagen (PIIANP) and cartilage degradation - urinary carboxy-terminal crosslinked telopeptide of type II collagen (CTX-II) 1.3. synovial abnormality: synovial inflammation - matrix metalloproteinase 3 (MMP3) and angiogenesis in pannus - vascular endothelial growth factor (VEGF) 2. SAA and fibrinogen 3. IL-6, sIL-6R, and sgp130 4. RF and anti-CCP antibodies 5. Anti-IL-6 autoantibodies (included as part of the PK assay) and ANA • Clinical variables: Change in DAS28 will be used to assess clinical activity. • Safety Variables: 1. AEs and SAEs 2. Vital signs (including BP, HR, respiratory rate, and temperature) 3. ECG monitoring 4. Clinical laboratory tests as per protocol: hematology, coagulation, | — |
Countries
Germany
Outcome results
None listed