Biogen

Author Of 2 Presentations

Clinical Outcome Measures Poster Presentation

P0102 - KonectomTM smartphone-based digital outcome assessment of cognitive and motor function in multiple sclerosis (ID 815)

Speakers
Presentation Number
P0102
Presentation Topic
Clinical Outcome Measures

Abstract

Background

The next generations of MS therapies aim at enhancing remyelination, protecting neurons/axons and altering the slowly progressive course of MS from its inception. To evaluate their efficacy, it is essential to develop novel, patient-centric outcome assessments that can quantify patient’s function with high frequency in their everyday life.

Objectives

To develop a digital solution that enables patients to quantitatively self-assess their function at high frequency in free-living environment in complement to in-clinic supervised administration and derive outcome measures that are able to detect the subtle changes during MS evolution.

Methods

KonectomTM smartphone application was designed and developed with patient-focused user experience insights to assess cognition, upper extremity function, ambulation/mobility and MS-related quality of life. To optimize accuracy and adherence of self-assessments, tutorials, vocal instructions and completion reward features were built into the app. KonectomTM was developed under IEC 62304 / ISO 13485 standards. KonectomTM digital outcome assessments (DOAs) will derive digital features processed from iPhone X accelerometer, gyroscope, touch, force touch, and GPS sensor information. KonectomTM formal usability study was completed in September 2019, in Chicago and in Paris (N=14 participants). KonectomTM is being evaluated in two Phase 2 studies in patients with relapsing MS (NCT04079088, N=300, 72 weeks of treatment period; undisclosed RMS Ph2 study).

Results

KonectomTM DOAs include 9 active test modules (mood/physical state 5-point Likert scale, multiple sclerosis impact scale 29-item questionnaire version 2 [MSIS-29v2], cognitive processing speed test, pinching test, drawing test, grip force test, static balance test, U-turn test and 6-min walk test) and a passive continuous monitoring of mobility behaviour. In the user experience testing, KonectomTM received a system usability scale (SUS, range 0-100, mean [SD]) score of 87.7 [8.7] which is much above the benchmark average of smartphone applications with a likelihood to recommend (LTR, range 0-10, mean [SD]) of 8.1 [2.0]. Results were consistent between French and US participants.

Conclusions

KonectomTM provides a patient-centric modular digital platform for ecological monitoring of neurological disability in MS clinical trials and real-world use with potential to be extended to other neurological disorders affecting cognitive and motor functions

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Clinical Trials Poster Presentation

P0186 - A Phase 1 study of BIIB091, a Bruton’s tyrosine kinase (BTK) inhibitor, in healthy adult participants: preliminary results (ID 390)

Abstract

Background

Bruton’s tyrosine kinase (BTK) is a key signalling node downstream of the B‑cell receptor (BCR) in B cells and Fc receptors (FcRs) in myeloid cells. Selective BTK inhibition may be beneficial for the treatment of MS by preventing B-cell and myeloid cell activation without immune cell depletion. BIIB091 is an orally active, selective, reversible (noncovalent), small molecule inhibitor of BTK in Phase 1 clinical development for the treatment of MS.

Objectives

Assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of BIIB091 in healthy adult participants.

Methods

This was a Phase I, randomized, double-blind, placebo-controlled, single ascending dose (SAD) and a multiple ascending dose (MAD) study in healthy adult participants (NCT03943056). Admitted participants were randomly assigned to BIIB091 or placebo (6:2). Participants received study drug orally at single dose levels of 50, 150, 300, 600, or 1200 mg in the fasted state during the SAD part. Participants completing 300 mg fasted dosing continued into a second period and received single dose 300 mg with a high fat meal. A separate group of participants enrolled in the MAD part and received doses of 50, 150, or 300 mg twice daily (BID) for 13 days, and a single dose on the morning of day 14. Safety (adverse events [AEs], vital signs, electrocardiograms [ECGs] and laboratory abnormalities), tolerability, and PK measures were assessed. The trial was ongoing as of February 2020. Preliminary results summarized here are based on a blinded data cut-off as of 20 Dec 2019, and include completed SAD cohorts, and 2 of 3 planned MAD cohorts.

Results

56 participants enrolled in the study (n=40 in SAD, n=16 MAD) and contributed to this analysis as of the data cut-off date. No deaths, serious AEs, severe AEs, cardiac related AEs, or AEs leading to study discontinuation were observed. All AEs were mild in severity. No clinically relevant changes in vital signs were reported as of the data cut-off date. BIIB091 PK was approximately dose linear, with median time to maximum plasma concentration ranging from approximately 0.8 to 1.4 hours after fasted dosing in SAD cohorts, with modest accumulation after multiple dosing. Food reduced Cmax variability and increased AUC.

Conclusions

BIIB091 was well tolerated at single doses up to 1200 mg. No dose limiting clinical AEs were identified in the MAD as of the data cut-off. Complete study results will be described in the poster. Preliminary safety and PK profile supports continued development of BIIB091 for the treatment of MS.

Supported by: Biogen

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