Clinical trials

Information on our clinical trials

At a glance

Active, recruiting
Interventional study
Involves brain surgery
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumbar punctures

About the study

HD Gene TRX2 is a phase 1b/2 study sponsored by UniQure investigating the safety and efficacy of AMT-130 in adults with early manifest Huntington´s disease. AMT-130 is a vurak vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, that aims to decrease the production of the toxic mutant (mHTT) and the wild type huntingtin protein.

This drug has already been investigated in a proof-of-concept study (HD Gene TRX1) recruiting 26 participants in the United States, without safety concerns.

In HD Gene TRX2 all participants will receive AMT-130 either at a lower or higher dose. The study drug is administered once by an intracranial neurosurgical procedure. Participants will be monitored for five years post-surgery in a series of study visits that will assess their physical and neurological health.

Primary outcome

Safety and tolerability of AMT-130

Secondary outcomes

Duration of AMT-130 in the brain
Clinical changes in response to AMT-130
Changes in imaging and fluid biomarkers in response to AMT-130

What is involved?

Following a screening period participants will receive the study drug through intracranial surgery. There will be monthly visits with regular MRIs, lumbar puncture, blood extraction and physical/neurological exam as well as further tests to evaluate safety during an initial period of five years. The visits will happen every three months during the first 18 months and every six months thereafter.

Who can take part?

Early manifest patients with ≥40 CAG repeats aged between 25 and 65 years without significant medical conditions apart from Huntington´s disease

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT05243017

PIVOT HD (Recruiting)

At a glance

Active, recruiting
Interventional study
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumbar punctures

About the study

PIVOT HD is a phase 2a study sponsored by PTC therapeutics. It investigates the safety and pharmacodynamics of PTC518 in patients with prodromal or very early Huntington’s disease. PTC 518 is an small molecule that has shown to decrease the concentrations of the toxic mutant (mHTT) and the wild type huntingtin protein. This molecule has already been tested in a study with healthy volunteers without significant safety concerns. Participants in this study will receive the study drug at different doses, or placebo, once daily during 12 weeks.

Primary outcome

Safety and tolerability of PTC518
Secondary outcomes
Changes in blood total huntingtin protein at the end of the study
Changes in cerebrospinal fluid mHTT protein at the end of the study
Changes in blood Huntingtin mRNA during the study

What is involved?

Following a screening period participants will receive the study drug. There will be visits every four weeks with MRIs, lumbar puncture, blood extraction and physical/neurological exam as well as further tests to evaluate safety during an initial period of 12 weeks.

Who can take part?

Patients with prodromal or very early HD, older than 25 years, with CAG repeats 42 to 50. Patients will need to have a score between 0.18 and 4.93 in the normalised version of the HD prognostic index and absent of significant medical or neurological conditions.

Link to clinicaltrials.gov: https://clinicaltrials.gov/study/NCT05358717

Generation HD2 (Recruiting)

At a glance

Active, recruiting
Invterventional study
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumlar puntures

About the study

Generation HD2 is a phase 2 study sponsored by Roche. It investigates the safety, biomarkers, and efficacy of Tominersen compared with placebo in participants with prodromal and early manifest Huntington's Disease. Tominersen is an antisense oligonucleotides, which has been shown to lower levels of the toxic mutant HD protein in previous clinical trials by interfering with its production. Participants will receive Tominersen, at different doses, or placebo every 16 weeks via lumbar puncture.

Primary outcome

Safety and efficacy of Tominersen

Secondary outcomes

Changes in cerebrospinal fluid mHTT protein at the end of the study
Changes in cerebrospinal fluid NfL at the end of the study
Changes in immune response to Tominersen during the study

What is involved?

Following a screening period participants will receive the study drug or placebo every 16 weeks via lumbar puncture. Visits will include MRIs, blood extraction, physical/neurological exam as well as further tests to evaluate safety and efficacy.

Who can take part?

Patients with prodromal or very early HD, aged between 25 and 50 years, with a CAG age product score between 400-500 and absent of significant medical or neurological conditions.

Link to clinicaltrials.gov: https://clinicaltrials.gov/study/NCT05686551

SHIELD HD (Not recruiting)

At a glance

Active, not recruiting
Observational study
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumbar punctures

About the study

SHIELD HD is a Triplet Therapeutics sponsored international, multisite, prospective, longitudinal cohort natural history study to assess the natural history of HD and its biomarkers that are associated with modulation of the number of cytosine-adenine-guanine (CAG) repeats in the mutant Huntingtin (HTT) gene.

Approximately 60 patients will be enrolled into the study and followed for up to 24 months at clinical sites in North America and Europe.

The results of this study will inform assessments for a future interventional treatment trial.

Primary outcome

To assess DNA damage repair (DDR) gene expression in accessible biofluids and disease trajectories for established and novel biomarkers and clinical outcomes

Secondary outcome

Compare rates of change in biomarkers for disease progression

What is involved?

The study lasts two years with regular visits to perform neurological and physical exam alongside MRI imaging of the brain and lumbar punctures. These results will inform the design of a future interventional clinical trials by Triplet Therapeutics targeting MSH3, a gene involved in somatic instability in HD.

Who can take part?

Patients between 18 and 63 years of age and with a CAG repeat length ≥39 in the HTT gene

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04406636

Natural History Study (Completed)

At a glance

Completed
Observational study
Involes cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumbar puntures

About the study

The HD Natural History Study monitors 100 patients with early Huntington’s disease over a period of 15 months with clinical assessments, lumbar punctures and magnetic resonance of the brain.

The outcomes for this study include the change from baseline in clinical measures, biomarkers of neuronal injury and in brain atrophy. The change in CSF mutant Huntingtin levels from baseline will also be measured.

What is involved?

The study lasts for 15 months and includes an initial screening visit to determine eligibility. For eligible participants further four clinic visits take place with lumbar punctures, MRI brain scans, blood tests, physical, neurological examinations and vital sign measurements. Participants are also required to complete daily assessments using a smart phone at home and wearing a smart watch.

After study participation, eligible participants will be offered to join a Roche-sponsored study of an experimental drug called RG6042 which is being tested for the treatment of HD.

Who can take part?

Patients between 25 and 65 years of age with stage I or stage II Huntington’s disease.

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03664804?term=Roche&cond=Huntingt...

VIBRANT-HD (Completed)

At a glance

Completed
Interventional study
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves lumbar punctures

About the study

VIBRANT-HD is a Novartis sponsored phase 2 dose range finding study investigating Branaplam in adults with Huntington’s disease. Branaplam is an orally bioavailable small molecule that has shown to affect the splicing of the Huntingtin mRNA, and may decrease the concentrations of both the mutant (mHTT) and the wild type huntingtin protein in HD gene carriers.

This drug has already been tested in children with Spinal Muscular Atrophy without safety concerns.

VIBRANT-HD will enrol participants with early manifest HD who will be randomised into Branaplam or placebo at different doses. Following one year of blinded follow up all participants will roll over into an Open Label Extension study where they will all receive the active drug for one year, although further follow up may be initiated depending on the results.

Primary outcome

Reduction of mHTT protein in cerebrospinal fluid (CSF)
Number of treatment emergent adverse events

Secondary outcomes

Investigating change in different clinical, imaging and fluid biomarkers

What is involved?

Following a screening period participants will to receive the study drug once a week through oral administration. There will be monthly visits with regular MRIs, lumbar puncture, blood extraction and physical/neurological exam as well as further tests to evaluate safety

Who can take part?

Early manifest HD patients with ≥40 CAG repeats, without significant concomitant medical conditions.

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT05111249

GEN EXTEND (Completed)

At a glance

Completed

About the study

A Roche sponsored phase III clinical trial evaluating the efficacy and safety of Tominersen (RG6042), an investigational drug that lowers mutant Huntingtin in the cerebrospinal fluid (CSF) of Huntington’s disease patients.

This trial recruited 791 ambulatory Huntington’s disease patients between 25 and 65 years of age with CAP score greater than 400 across 97 study sites. Patients were randomized into three groups. One group received Tominersen every two months, another group received alternating doses of the drug or placebo every two months and a last group received only placebo every two months. Participants were regularly assessed with lumbar punctures, MRI brain scans, blood tests, physical, neurological examinations and vital sign reviews. Participants were also required to complete daily assessments using a smart phone and wear a smart watch.

The trial was discontinued on 22 March 2021 following the independent Data Monitoring Committee’s recommendation that all dosing be stopped. Patients continue to be followed for safety and efficacy outcomes as per protocol. No new or emerging safety signals were identified in the review of the data from this study.

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03761849

GEN-HD1 (Discontinued)

At a glance

Discontinued
Drug trial
Involves cognitive tests
Involves blood tests
Involves magnetic resonance imaging (MRI)
Involves repeated lumbar punctures