Relapsing forms of multiple slerosis MedDRA version: 9.1 Level: LLT Classification code 10048393 Term: Multiple sclerosis relapse
Conditions
Interventions
Product Name: CDP323
Product Code: CDP323
Pharmaceutical Form: Capsule, hard
CAS Number: 455264-30-9
Current Sponsor code: CDP323
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
UCB Pharma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • written informed consent; • being of legal capacity and able to understand the nature of the study and its potential risks; • being willing to comply with the study's safety precautions and with the intended drug-free follow-up at the study site 12 months after the last intake of study medication; • diagnosis of MS according to the revised McDonald criteria (Polman et al. Ann Neurol 2005;58:840-6); • relapsing form of MS, i.e., RRMS or SPMS (with superimposed relapses) according to Lublin and Reingold (Neurology 1996;46:907-11); • screening EDSS score of 0-6.0, inclusive; • female and male subjects aged 18-60 years inclusive at time of informed consent; • Clinical relapse activity in the 12 months before screening and documented in the subject's medical records; • active disease, defined by the presence of either, • at least nine lesions on the screening T2 scan or, • Gd enhancement on the screening T1 scan or, • Gd enhancement on an MRI scan during the past 12 months or, • at least two new T2 lesions during the past 12 months; • failed prior treatment with beta-interferons or glatiramer acetate due to lack of efficacy or tolerability; • female subjects of childbearing potential must agree to practice one of the following contraception method: • double-barrier contraception (i.e.,using a male or female condom with spermicide, or diaphragm or cerivcal cap with spermicide) or • any contraceptives containing estrogens plus one of the following: diaphragm or cervical cap with spermicide, male or female condom with spermicide or • intrauterine devices or • contraceptives containing progestins only,e.g., etonogestrel or levonogestrel or medroxyprogesterone or norethindrone or • monogamous relationship with vasectomized partner or • sexual abstinence Note: Lack of childbearing potential will be considered under these circumstances: • post-menopausal for at least two years, • bilateral oophorectomy, ovariectomy, salpingectomy, or tubal ligation, • hysterectomy; • congenital sterility. • negative pregnancy tests at screening and at baseline for female subjects of childbearing potential; • full immunocompetency: CD4+ lymphocyte count >500/mm3; • JC viral DNA particles undetectable in blood at two separate measurements. 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • type of MS other than relapsing; • any disease other than MS that could better explain the subject's signs and symptoms; • any conditions that could interfere with the contrast-enhanced MRI, including an estimated glomerular filtration rate (eGFR) 450 ms (in case of doubt, UCB's responsible medical officer will be consulted and a joint documented decision will be made between investigator and UCB's medical officer); • any significant deviation from reference ranges for hepatic function as defined by either SGOT, SGPT, GGT, or AP elevated 3-fold or higher beyond the upper limit of the reference range or total bilirubin elevated 2-fold or higher beyond the upper limit of the reference range; • signs of silent infections, including positive tests for HIV1, HIV2, or Hepatitis B or Hepatitis C, or tuberculosis; • any condition possibly interfering with drug absorption; • known allergy to gadolinium-DTPA, and/or ingredients of the study drug formulation; • history of severe AEs to any drug; • participation in any clinical drug trial within 30 days prior to screening; • concomitant treatment with the CYP1A substrates mexiletine, propafenone, theophylline, verapamil or warfarin or statins (e.g., atorvastatin), or rosiglitazone, pioglitazone, repaglinide, amodiaquine and any other compound metabolized primarily through cytochrome P450 2C8, or protease inhibitors (e.g., ritonvavir), systemic triazole antifungals (e.g., ketoconazole) for either their interference with transport protein systems or for their strong inhibition of the P450 cytochrome pathway, or these drugs known for their potential to interfere with cardiac repolarization: amiodarone, arsenic trioxide, bepredil, budipine, cisapride, chinidine (quinidine), chloroquine, chlorpromazine, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, sotalol, sparfloxacin, thioridazine • pre-treatment with the following substances prior to study participation within the following time frames: • at any time: rituximab, mitoxantrone or cyclophosphamide; total lymphoid irradiation; anti-lymphocyte monoclonal antibody treatment (e.g., anti-CD4, Campath-1H); cladribine, mycophenolate; • up to 30 days prior to baseline: any interferons, glatiramer acetate, corticosteroids and ACTH, IvIg, cyclosporine A, human antibodies, any other immunomodulating or immunosuppressive drugs including recombinant cytokines, any other putative or experimental MS treatment; any inoculation with attenuated live vaccines • six month prior to baseline: azathioprine or natalizumab. Treatment with natalizumab must not have been terminated due to lack of efficacy, however subjects with documented natalizumab neutralizing antibodies ma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the effects of 500 mg CDP323 twice daily on MS-related imaging parameters in subjects with relapsing MS (RMS) with the effects seen under placebo treatment in that population over a period of 24 weeks;Secondary Objective: - Compare CDP323's tolerability and safety in RMS subjects with placebo treatment in that population over a period of 24 weeks; - Compare the effects of CDP323 on the occurrence of relapses in RMS subjects with the effects seen under placebo treatment in that population over a period of 24 weeks; - Compare the effects of twice daily dosing of CDP323 vs once daily dosing of CDP323 including the related time course of a4/VCAM-1 binding between the two dosing regimen and placebo; - Characterize the main pharmacokinetic parameters of CDP323 and its metabolites in subjects suffering from RMS; - Assess potential withdrawal effects after termination of treatment with CDP323.;Primary end point(s): Primary Efficacy Variable Cumulative number of newly active lesions over 24 weeks as seen on standardized brain MRI scans. The following lesions are considered newly active: • new gadolinium (Gd) enhancement on T1-weighted images; • non-enhancing on T1-weighted images but new on T2-weighted images; • new enlargement on T2-weighted images but non-enhancing on T1-weighted images. Pharmacokinetic and Pharmacodynamic Variables • for all subjects, plasma concentrations of CDP323, CT7758, and CT533652-00 will be determined from samples taken during specified time points; a 'sparse' sampling schedule will be followed • population-kinetic methods may be used to describe derived pharmacokinetic parameters for CDP323, CT7758, and CT533652-00 • in a subset of centers suitable to set up the logistics for pharmacodynamic tests markers, such markers including VCAM1 binding may be determined; in addition, subjects participating in this pharmacodynamic sub-study will be asked to also undergo a more intense pharmacokinetic sampling schedule to allow an in | — |
Countries
Belgium, Finland, France, Germany, Hungary, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed