Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety.Results: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time.Conclusions: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found.Classification of evidence: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS

Topiramate in the treatment of Myoclonic-Astatic Epilepsy in children: a retrospective hospital audit

BACKGROUND: Myoclonic-Astatic Epilepsy (MAE) usually starts before five years of age and is associated with very frequent seizures and is highly resistant to treatment. AIM: To investigate the outcome of adjunctive topiramate (TPM) therapy in children with a diagnosis of MAE syndrome. Subjects AND METHODS: In an outpatient setting, case notes of 27 children who received TPM were retrieved and analysed. RESULTS: Records of 6 children with MAE, who were experiencing 2-8 atonic seizures daily before starting TPM were studied. Improvement was noted after addition of TPM (mean dose at steady-state 7.4±2.5mg/kg/day) to the regimen of 1-3 anti-epileptic drugs they were receiving concurrently. All but one child improved following the titration period: one had 50-80% improvement in the frequency of atonic seizures and three had over 80% improvement. However, one child who showed over 80% improvement and was free of atonic seizures, later developed increased frequency of other seizure types. In one child there was no significant improvement. Improvement has been sustained for over 6 months in three patients and over 4 months in one; three have continued TPM. TPM was stopped in three patients (reduction in seizure control/no improvement). CONCLUSIONS: This study supports the efficacy of TPM in controlling atonic seizures in MAE and indicates that it should be considered as an add-on drug in the management of this 'difficult-to-treat' epileptic syndrome

Challenges and practical recommendations for successfully recruiting inactive, statin-free older adults to clinical trials

Objectives: to outline the challenges and provide practical recommendations for recruiting inactive, statin-free older adults to facilitate feasible study designs. Data was obtained from a double-blind randomised-controlled clinical trial investigating the effects of acipimox versus placebo on muscle function and metabolism in older (65-75 years), inactive, statin-free males. The initial recruitment target was 20 volunteers within 12 months (November 2016-November 2017).Results: recruitment occurred via the Exeter 10,000 database containing 236 'eligible' males, a Facebook campaign reaching > 8000 ≥ 65 years old males, 400 directly-addressed letters to ≥ 66 year old males, > 1500 flyers distributed within the community, > 40 emails to local community groups, 4 recruitment talks, 2 magazine adverts and 1 radio advert. Widespread recruitment efforts reaching > 120,000 people led to the recruitment of 20 volunteers (18 completed the clinical trial) within a 25-month timeframe, highlighting the challenge of the timely recruitment of inactive, statin-free older adults for clinical trials. We recommend recruitment for future clinical trials should take a multi-pronged approach from the outset, prioritising the use of volunteer databases, Facebook campaigns and delivering recruitment talks