The PERSPECTIVE Program is evaluating the safety and efficacy of an investigational oral drug in adults with early Huntington’s disease. The program is comprised of 3 clinical research studies:

1. Dimension Study: 20 weeks
2. Surveyor Study: 6 weeks
3. PURVIEW Study (Open-Label Study for those that have completed either Dimension or Surveyor): 1 - 1.5 years

The investigational drug, SAGE-718, is believed to target cognitive symptoms. This study is open to individuals between the ages of 25-65, have a genetically confirmed diagnosis of Huntington’s Disease with CAG expansion of 36 or higher, and be ambulatory (use of a cane or walker is acceptable) and able to travel to the study center.

If you are interested in learning more about any of these studies, please contact Etta Bernard at [email protected] or 410-614-7671

The previous study GENERATION HD1 sought to test the safety and effectiveness of tominersen for reducing disease progression in people with manifest (diagnosed) HD aged between 25 and 65 years old. In this study, participants received either a placebo (an inactive substance), tominersen once every 8 weeks, or tominersen once every 16 weeks. To judge the effectiveness of tominersen, we measured changes in TFC (total functional capacity) and cUHRS (composite unified Huntington’s disease rating scale) – two scales used by doctors to measure how much HD impacts a person’s disease, movement, behavior, daily functioning, and cognition.

Further examination of the GENERATION HD1 study results (known as a ‘post-hoc’ analysis) revealed a potential reason to remain hopeful – tominersen appeared to benefit younger adults with less severe HD when given less frequently (once every 16 weeks). While these results are encouraging, the GENERATION HD1 study was not set up and conducted with this particular group of participants in mind. And so the study did not produce enough data for us to say for sure whether or not tominersen may be an effective HD treatment for this group.

That is why our site is participating in the GENERATION HD2 study. GENERATION HD2 will test tominersen in younger adults between the ages of 25-50 who are in the earlier stages of HD and will investigate lower doses than those used in the previous trial.

If you are interested in learning more about this study, please contact Etta Bernard at [email protected] or 410-614-7671. Q&A video with Dr. Jee Bang and more information about Generation HD2 study.

The main purpose of this observational study is to collect cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord, which is needed to study biomarkers to see which biomarkers influence HD’s pathophysiology and progression, as well as how biomarkers differ between HD and non-HD participants. CSF can be used to provide information about the brain and the nervous system that is impossible to obtain in any other way. CSF is collected by a procedure called a lumbar puncture or spinal tap. This is a commonly performed procedure that takes around 30 minutes. Family members with a positive or negative HD status, or family not related through blood (i.e. spouses and partners) may participate. In addition, biomarkers may help design and guide future research studies and clinical trials as well as help us better understand who will most likely benefit from a particular treatment.

For information about this study, please contact Etta Bernard at [email protected] or 410-614-7671

Enroll-HD is a multi-site clinical observational study that assess its participants on an annual basis. There are over 13,000 active participants worldwide, at 148 sites in 15 countries. Types of assessments used includes cognitive, behavioral, motor, and physiological, as well as demographic information and HD family history. You will also have a blood draw. Both people with and without HD can participate – this includes pre-symptomatic and symptomatic patients, those with unknown HD status, and family members. Furthermore, this study leads as a platform for future HD clinical research.

For information about this study, please contact: Etta Bernard ([email protected])

uniQure is conducting a double-blinded Phase I/II gene-based therapy known as AMT-130. AMT-130 is administered directly into the brain tissue using a minimally invasive brain surgery technique. The main purpose of this study is to find a safe dose of AMT-130 in adults who have early stage HD. It will also look at how the body processes AMT-130 and how it might affect the progression of HD. This study is open to patients with a clinical diagnosis of early-manifest HD and between the ages of 25 to 65 years old. A total of 26 patients from the United States will be enrolled, with 16 receiving the treatment of AMT-130 under general anesthesia (“Treated Group”) and the remaining 10 not receiving the treatment (“Imitation Group”). The main part of the study lasts for 18 months, with additional annual visits out to 5 years for continued safety follow up. Procedures will include clinic visits, assessments of physical and neurological health, a neurosurgical procedure, lumbar punctures, brain scans, and samples from body fluids. More information from the uniQure website: http://www.uniqure.com/patients/phase-1-2-clinical-trial-of-amt-130.php.

The purpose of this study is to compare the effects, good and/or bad, of RO7234292 (also known as RG6042) in study participants with Huntington’s disease (HD). RO7234292 is an investigational drug from a group of drugs known as anti-sense oligonucleotides (ASO), which are man-made stretches of DNA which stop the “messenger” RNA from instructing cells to make proteins.

HD is caused by toxic mutant HTT (called “mHTT”) protein. RO7234292 has shown to lower levels of this toxic protein in the first clinical trial by interfering with its production. It is hoped that by reducing mHTT protein, progression of disease can be slowed or stopped. The current study aims to test this idea.

The use of RO7234292 in this research study is investigational. The word “investigational” means that RO7234292 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of HD or any other condition. The FDA is allowing the use of RO7234292 in this study.

In this study, participants will receive RO7234292 or placebo (contains no active ingredient) administered into the spinal fluid at each study visit. Some participants will receive alternating doses of RO7234292 and placebo at each study visit.

Study Director: Jee Bang, MD, MPH
Lead Coordinator: Kia Ultz
Sponsor: Genentech / Roche
Recruiting? Yes
ClinicalTrials.gov Identifier: NCT03761849
Conditions Studied: Early Manifest Huntington’s disease (HD)
Intervention: RG6042 and/or placebo
Duration of Participation: Approximately 26 months
Frequency of Visits: Once every other month

Study Details

Inclusion Criteria:

• Manifest HD diagnosis, defined as a DCL score of 4
• Independence Scale (IS) score >= 70
• Genetically confirmed disease by direct DNA testing with a CAP score >400
• Clinical assessment to ensure individual has intact functional independence at baseline to maintain self-care and core activities of daily living (ADLs).

Exclusion Criteria:

• Any serious medical condition or clinically significant laboratory, or vital sign abnormality at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug, severe chorea

Study Visits includes:

• Lumbar puncture (also known as spinal tap)
• Blood draws and urinalysis
• Neuro, physical, and motor exams
• MRIs
• Cognitive assessments
• Questionnaires
• Medical and surgical history, and comorbid conditions
• Vital signs, including EKGs

This research is being done to explore and examine the relationship between the abnormal mutant huntingtin protein (thought to be the main cause of Huntington's disease) and the progression of your disease over time. This study is measuring a certain protein (called mutant huntingtin [mHTT]) together with other biological markers to better understand HD. This study in patients with early Huntington's disease (HD) will explore the ways in which the spinal fluid biological markers are related to the mHTT and the utility of recording clinical outcome measures via sensors contained in the Roche HD mobile app. This study is being conducted at approximately 17 sites worldwide, and seeks to enroll 100 individuals. No drug is being tested.

Study Director: Jee Bang, MD, MPH
Lead Coordinator: Etta Goldman
Sponsor: Genentech / Roche
Recruiting? No
ClinicalTrials.gov Identifier: NCT03664804
Conditions Studied: Early Manifest Huntington’s disease (HD)
Intervention: No drug intervention. However, participants who complete this study may be eligible to join the Open Label study for RG6042.
Duration of Participation: Approximately 18 months
Frequency of Visits: Screening and baseline done within a month of each other; future “visits” (alternating in clinic and via phone) every three months

Study Details

Inclusion Criteria:

• Age 25-65, Genetically diagnosed HD
• Manifest HD clinical diagnosis, defined as a DCL score of 4
• Genetically confirmed disease by direct DNA testing
• Must meet age, gender, and CAG repeat critera of needed participants. (All participants “match” a participant who completed the RG6042 Phase I/II study.)

Exclusion Critera:

• Any serious medical condition or clinically significant laboratory, or vital sign abnormality at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug, severe chorea

Study Visits includes:

• Lumbar puncture (also known as spinal tap)
• Blood draws and urinalysis
• Neuro, physical, and motor exams
• MRIs
• Cognitive assessments
• Questionnaires
• Medical and surgical history, and comorbid conditions
• Vital signs, including one EKG

The primary objective of Phase 2 is to evaluate the safety, tolerability and efficacy of monthly IV administration of VX15/2503 over 18 months and up to 36 months (subset of subjects) in Cohort B in subjects with late prodromal or early manifest HD. Efficacy assessments for Cohort B will include neuropsychological, clinical, motor, global measurement of change and imaging endpoints in a population of late prodromal and early manifest HD patients over 18 months and up to 36 months. This trial is being conducted at approximately 30 sites across the US and Canada, and seeks to enroll 240 individuals.

PROOF-HD is a Phase 3 clinical trial investigating the drug pridopidine as a treatment for Huntington’s disease. This study will enroll up to 480 people internationally with early-stage HD. To enroll, participants must be 25 or older and have a confirmed diagnosis of early stage, adult-onset HD. During the trial, participants will be randomly selected to receive either an oral capsule of 45 mg pridopidine or a placebo, used for comparison, taken two times a day. The study will last between 65 to 78 weeks (15 to 18 months), with an optional open-label extension phase – in which all participants will be given pridopidine - for patients who would like to continue treatment thereafter. Pridopidine was previously studied in other clinical trials (PRIDE-HD and OPEN-HART), which showed that it was overall well-tolerated by patients.

A: Symptomatic treatments reduce specific symptoms such chorea or depression. They do not change the underlying course of the disease. And they may take effect quite rapidly. For example, tetrabenazine and its derivatives begin to work for chorea almost immediately. But they also lose their effectiveness when the medication is stopped. Disease-modifying treatments would actually alter the underlying progression of degeneration in the brain. Thus their effectiveness might take many months to be evident, but would be long-lasting.

A more familiar example of these distinctions might be bronchitis from a bacterial infection. Symptomatic treatments like cough suppressants would work quite quickly (minutes to hours), but would not change the course of the illness. By contrast, an antibiotic (targeted at the correct infectious organism) might take several days to work, but would cure the underlying infection.

A: There are none so far. That’s what makes finding disease-modifying treatments the key task in HD research.

A: The mutant HD gene Huntingtin (i.e. the expanded CAG repeat) codes for a mutant Huntingtin protein, via an intermediary information-carrying molecule called messenger RNA. The mutant Huntingtin protein is believed to be the major cause of damage within neurons, leading to neurodegeneration within the striatum and other areas of the brain. New molecular biology techniques make it possible to attempt to interfere with the function of the messenger RNA molecule leading to a reduction in the levels of the mutant Huntingtin, and thus a decrease in the amount of neurodegeneration. This would, for the first time, actually modify the course of the disease. Ultimately the symptoms would be reduced as well. This overall approach is often called ‘RNA-interference’ since it interferes with the function of the messenger RNA, thus achieving ‘Huntingtin-lowering’ (or if very highly effective, ‘Huntingtin-silencing’). There are a variety of strategies being pursued to achieve this goal. Two of the major ones involve ‘antisense oligonucleotides’ or ‘viral vectors’.

A: They are DNA molecules specially designed to target the Huntingtin messenger RNA and cause its degradation, thus achieving Huntingtin-lowering and disease-modifying therapeutics. Because they are large molecules, they do not cross the barrier around the brain so they cannot be taken by mouth or even by intravenous injection. They could be injected directly into the brain (as was done in animal studies) but the more typical strategy is to inject them via a small needle into the lower back into the fluid that surrounds the brain and spinal cord known as the cerebrospinal fluid. This is called ‘intrathecal administration’.

A: Ionis is the company that developed HTTRx which is a Huntingtin-lowering drug using intrathecal administration of an antisense oligonucleotide agent in its early trials. They were “first in human” studies designed to test different doses and show safety. They also apparently saw a reduction in mutant Huntingtin levels in the cerebrospinal fluid (CSF). This is clearly a major accomplishment. However it is important to appreciate that this was a short trial in a small number of patients, most of whom got a relatively low dose. The initial press release did not say how much reduction of mutant Huntingtin was achieved, and did not report whether or not there were any clinical changes (though in such a small short trial, one would not necessarily expect to detect clinical effect). We don’t know how well changes in huntingtin levels in the CSF would reflect huntingtin levels in the relevant parts of the brain. Most importantly, we don’t yet know whether these changes would be sufficient to cause clinical benefit. Nevertheless, this is a novel and very promising approach to the goal of disease-modifying therapy.

A: Larger trials now need to be conducted in many more patients with an appropriate placebo group. Ionis, the company that developed HTTRx, is a relatively small company and does not have the infrastructure to conduct a large clinical trial. So the next trials will be sponsored by Roche, a large pharmaceutical company, and are currently in the active planning phase. We are hoping that Johns Hopkins, building on our participation in the ‘HDClarity’ study, will be a site in this larger trial of HTTRx, to see if it can really modify the underlying disease, and thus slow the clinical progression.

A: HDClarity is a research study currently underway here at Hopkins in which cerebrospinal fluid (CSF) is collected to study the progression of HD using a routine procedure called a lumbar puncture or spinal tap, which takes about 30 minutes. The goal is to quantify levels of mutant Huntingtin and other biomarkers. A biomarker is anything that can be measured, such as chemical substances in the CSF that reflect neuronal injury, in order to help us understand HD.

Biomarkers may help guide future research studies and clinical trials, as well as help us better understand who will most likely benefit from a particular treatment. CSF can be used to provide information about the brain and nervous system that is impossible to obtain in any other way. Individuals with a positive or negative HD genetic test status, or family not related through blood (i.e. spouses and partners) may participate.

We are actively enrolling for the HDClarity study, and were the first US site (and as of December 2017 the only U.S. site actively enrolling). Participants must be part of the ongoing observational study, called ENROLL-HD, which just involves tracking routing motor, cognitive and emotional changes over time.