228PD201 Phase 2a study testing BIIB054 for Parkinson’s Disease

• Research type

  Research Study

• Full title

  A Multicenter, Randomized, Double-Blind, Placebo-Controlled\nStudy, with an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson’s Disease

• IRAS ID

  238640

• Contact name

  Thomas Foltynie

• Contact email

  t.foltynie@ucl.ac.uk

• Sponsor organisation

  Biogen Idec Research Limited

• Eudract number

  2016-004610-95

• Clinicaltrials.gov Identifier

  NCT03318523

• Duration of Study in the UK

  4 years, 7 months, 21 days

• Research summary

  Summary of Research
  Biogen is developing BIIB054 for the treatment of Parkinson’s Disease. BIIB054 targets aggregated forms of alpha-synuclein (α-syn), the primary structural component of the Lewy bodies (LBs) and Lewy neuritis (LNs) which are the pathological hallmarks of Parkinson’s Disease. The distribution, density, and associated severity of LBs is associated with the severity of the clinical disease. Early stage Parkinson’s Disease patients will be selected for this study as BIIBO54 may be more effective in modifying the course of the disease when less neuronal damage is evident and the spread of disease pathology is more limited\n\nThis is a Phase 2a, randomised, double-blind, parallel-group, placebo-controlled study (Year 1) with an active-treatment dose-blinded period (Year 2) that will examine the safety, Pharmacokinetics (the study of the bodily absorption, distribution, metabolism, and excretion of BIIB054)and Pharmacodynamics (the study of the biochemical and physiologic effect of BIIB054), administered every 4 weeks via intravenous (IV) infusion to adults with Parkinson’s Disease. The primary objective of the study is to evaluate the dose-related safety of BIIB054. Approximately 311 participants will be enrolled at about 85 sites globally.

  Summary of Results
  What were the study results?
  When the study ended, Biogen reviewed the data and created a report of the results. This is a summary of that report. Below is an overall summary of the results and the key questions researchers asked during the study. The individual results of each participant might be different and are not in this summary.

  Did BIIB054 slow down the disease progression at Week 52 and Week 72 of treatment?
  During the study, researchers checked the symptoms participants had at different times. They checked symptoms at the start of the study, at Week 52, and at Week 72. Researchers used a scale called the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to measure PD symptoms.

  What is MDS-UPDRS?
  It is a scale that measures impairment and disability in people living with Parkinson’s disease. A higher score means more severe Parkinson’s disease symptoms.
  The scale has 4 parts, but researchers only used the first 3:
  • Part I: Measures non-motor experiences of daily living
  • Part II: Measures motor experiences of daily living
  • Part III: A motor symptoms examination
  • Part IV*: Motor complications of PD
  *Part IV was not used because complications usually don’t start in the early phase of Parkinson’s disease.

  A description of the first three parts of the MDS-UPDRS is given below.

  Part 1: Researchers checked participants for non-motor symptoms that included:
  • Hallucinations
  • Feeling lightheaded when standing
  • Tiredness
  • Depression and anxiety
  • Constipation
  • Sleeping problems
  • Difficulty in controlling certain urges, like cleaning or gambling
  
  Parts 2 and 3: In Part 2, participants reported motor experiences of day-to-day activities and in Part 3, researchers examined participants with these motor symptoms that included difficulty with:
  • Getting out of bed or a chair
  • Speaking
  • Handwriting
  • Moving slowly or having difficulty starting to move
  • Tremor
  • Walking and balance
  • Eating
  • Doing hobbies and other activities

  Scores could range from 0 to 236, with higher scores meaning that a participant had more PD symptoms.
  A small number of participants left the study early. As a result, there are fewer participants in each group as the study progressed.
  The average MDS-UPDRS scores for participants at the start of the study are given below.
  Placebo – 100 participants
  MDS-UPDRS Score: 32

  BIIB054 250 mg – 55 participants
  MDS-UPDRS Score: 32

  BIIB054 1250 mg – 102 participants
  MDS-UPDRS Score: 33

  BIIB054 3500 mg – 100 participants
  MDS-UPDRS Score: 33

  The change in MDS-UPDRS scores from the beginning of the study to Week 52 are given below.
  Placebo – 82 participants
  Increase in MDS-UPDRS Score: 11

  BIIB054 250 mg – 41 participants
  Increase in MDS-UPDRS Score: 10

  BIIB054 1250 mg – 89 participants
  Increase in MDS-UPDRS Score: 11

  BIIB054 3500 mg – 77 participants
  Increase in MDS-UPDRS Score: 11

  The change in MDS-UPDRS scores from the beginning of the study to Week 72 are given below. For these results, the scores are shown for the Early Start and Delayed Start groups separately.

  Delayed Start – 68 total participants

  Placebo to BIB054 250 mg – 12 participants
  Increase in MDS-UPDRS Score: 6
  Placebo to BIB054 1250 mg – 30 participants
  Increase in MDS-UPDRS Score: 7
  Placebo to BIB054 3500 mg – 26 participants
  Increase in MDS-UPDRS Score: 8
  Early Start – 159 total participants
  BIB054 250 mg – 32 participants
  Increase in MDS-UPDRS Score: 7
  BIB054 1250 mg – 62 participants
  Increase in MDS-UPDRS Score: 9
  BIB054 3500 mg – 65 participants
  Increase in MDS-UPDRS Score: 7
  What adverse events happened during the study?

  This section is a summary of the medical problems the participants had during the study. A lot of research is needed to know whether a study drug causes a medical problem, also called an adverse event. An adverse event is considered “serious” when it results in death, is life-threatening, causes lasting problems, or requires hospital care. When new drugs are being studied, researchers keep track of all adverse events that participants have during the study. Not everyone experiences the same adverse events.
  One goal of this study was to learn more about the adverse events of BIIB054.
  Only those adverse events that the Investigator considered related to treatment with BIIB054 or placebo are included in this section. This section includes only the participants who received at least 1 dose of study medication.

  Did any adverse events happen during this study?
  The summary of adverse events for each group up to Week 52 of the study is shown below.

  Placebo Group – 100 participants
  21 participants (21%) had adverse events.
  1 participant (1%) had a serious adverse event.
  1 participant (1%) stopped treatment because of an adverse event.

  BIIB054 250 mg Group – 55 participants
  11 participants (20%) had adverse events.
  No participants had any serious adverse events.
  No participants stopped treatment because of an adverse event.

  BIIB054 1250 mg Group – 102 participants
  18 participants (18%) had adverse events.
  1 participant (1%) had a serious adverse event.
  1 participant (1%) stopped treatment because of an adverse event.

  BIIB054 3500 mg Group – 100 participants
  21 participants (21%) had adverse events.
  3 participants (3%) had serious adverse events.
  1 participant (1%) stopped treatment because of an adverse event.

  The summary of adverse events that happened in each group from Week 52 until the end of the study is shown below. A small number of participants left the study before Week 52, so they are not included in these results.

  Early Start – 246 total participants

  BIIB054 250 mg Group – 52 participants
  5 participants (10%) had an adverse event.
  1 participant (2%) had a serious adverse event.
  1 participant (2%) stopped treatment because of an adverse event.

  BIIB054 1250 mg Group – 100 participants
  10 participants (10%) had adverse events.
  No participants had any serious adverse events.
  No participants stopped treatment because of an adverse event.

  BIIB054 3500 mg Group – 94 participants
  10 participants (11%) had adverse events.
  No participants had any serious adverse events.
  1 participant (1%) stopped treatment because of an adverse event.

  Delayed Start – 96 total participants

  Placebo to 250 mg BIIB054 Group – 20 participants
  1 participant (5%) had an adverse event.

  Placebo to 1250 mg BIIB054 Group – 37 participants
  5 participants (14%) had an adverse event.

  Placebo to 3500 mg BIIB054 Group – 39 participants
  4 participants (10%) had an adverse event.

  No participants in the Delayed Start group had any serious adverse events or had to stop treatment because of an adverse event.

  No participants in any group died in this study due to an adverse event.

  What serious adverse events happened during the study?
  The serious adverse events that happened to participants up to Week 52 are listed below.
  Placebo Group – 100 participants
  1 participant (1%) had inflammation of the liver.

  BIIB054 250 mg Group – 55 participants
  No participants had any serious adverse events.

  BIIB054 1250 mg Group – 102 participants
  1 participant (1%) had inflammation of the membrane around the heart.

  BIIB054 3500 mg Group – 100 participants
  1 participant (1%) had an irregular, pounding heartbeat.
  1 participant (1%) had a mini stroke.
  1 participant (1%) had a growth within the skull and a tumor in the brain.

  The serious adverse events that happened to participants from Week 52 until the end of the study are listed below.

  In the Early Start group, 1 participant (2%) in the BIIB0054 250 mg group experienced a serious adverse event of a mini stroke after Week 52.

  In the Delayed Start group, no participants experienced any serious adverse events.

  What other adverse events happened during the study?

  Other non-serious adverse events that happened to participants up to Week 52 are listed below. Only adverse events that happened in at least 1% of participants taking BIIB054 are included.

  Placebo Group – 100 participants
  4 participants (4%) had headaches.
  2 participants (2%) had nausea.

  BIIB054 250 mg Group – 55 participants
  3 participants (6%) had headaches.
  2 participants (4%) had diarrhea.
  1 participant (2%) had dizziness.
  1 participant (2%) had tiredness.
  1 participant (2%) had nausea.
  1 participant (2%) had reddening of the face.

  BIIB054 1250 mg Group – 102 participants
  7 participants (7%) had headaches.
  3 participants (3%) had tiredness.
  2 participants (2%) had dizziness.
  1 participant (1%) had diarrhea.
  1 participant (1%) had nausea.
  1 participant (1%) had reddening of the face.

  BIIB054 3500 mg Group – 100 participants
  8 participants (8%) had tiredness.
  3 participants (3%) had chest discomfort.
  2 participants (2%) had headaches.
  2 participants (2%) had dizziness.
  2 participants (2%) had reddening of the face.
  1 participant (1%) had nausea.

  Other non-serious adverse events that happened to participants from Week 52 until the end of the study are listed below. Only adverse events that happened in at least 1% of participants who took BIIB054 are included.

  Early Start – 246 total participants

  BIIB054 250 mg Group – 52 participants
  No participants had adverse events that happened in at least 1% of participants.

  BIIB054 1250 mg Group – 100 participants
  1 participant (1%) had tiredness.

  BIIB054 3500 mg Group – 94 participants
  3 participants (3%) had tiredness.
  1 participant (1%) had headaches.

  Delayed Start – 96 total participants

  Placebo to 250 mg BIIB054 Group – 20 participants
  No participants had adverse events that happened in at least 1% of participants.

  Placebo to 1250 mg BIIB054 Group – 37 participants
  2 participants (5%) had headaches.

  Placebo to 3500 mg BIIB054 Group – 39 participants
  2 participants (5%) had headaches.

  How has this study helped patients and researchers?
  Researchers look at the results of many studies to decide which medicines work best and are safest for patients. This study helped researchers learn more about possible ways to treat Parkinson’s disease.

  Where can I learn more about the study?
  You can find more information about the study online at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C097e24ba50734ea3de7608da2127a14a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637858751333407615%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=8m0gSqWw698h36ypaZTfmALUX5PlHbzd8ikuF3z5qXk%3D&reserved=0. Once on the site, type NCT03318523 into the search box and click “Search”.
  You can also find more information online at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C097e24ba50734ea3de7608da2127a14a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637858751333407615%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=eiaZXpijjaNoFBZyYxuAiCGZSH%2B1GZJB7AvOxcTE4XU%3D&reserved=0. Once on the site, click “Home & Search,” then type: 2016-004610-95 in the search box and click “Search”.
  If you have questions about BIIB054 or the results of this study, please speak with the doctor or staff at the study research center.

  Official study title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, with an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson’s disease
  Biogen, the sponsor of this study, has its headquarters in Cambridge, Massachusetts (USA).
  The results presented here are for a single study. You should not make changes to your therapy based on these results without first consulting your doctor.

• REC name

  South West - Central Bristol Research Ethics Committee

• REC reference

  18/SW/0023

• Date of REC Opinion

  4 Apr 2018

• REC opinion

  Further Information Favourable Opinion