Early Manifest Huntington DiseasePhase 2VIBRANT-HDNCT05111249
A Dose Range Finding Study With Open-Label Extension to Evaluate the Safety of Oral LMI070/Branaplam in Early Manifest Huntington's Disease
A Phase 2 study testing Branaplam in people with Early Manifest Huntington Disease, run by Novartis Pharmaceuticals at 12 sites in 5 countries.
Trial summary
This is the first study of branaplam in adults with Huntington's Disease (HD) to determine the correct dose required to lower mutant huntingtin protein (mHTT) levels in the cerebrospinal fluid (CSF) to a degree expected to be efficacious over longer periods of time. Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Early Manifest Huntington Disease
- What is being tested?
- Branaplam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 8 Dec 2021to 27 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent must be obtained prior to participation in the study.
- Clinically diagnosed Stage 1 or 2 Huntington's disease with a diagnostic confidence level (DCL) = 4 and a United Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) >8 at screening.
- Genetically confirmed Huntington's disease, with presence of ≥40 cytosine-adenineguanine (CAG) repeats in the huntingtin gene.
- Male and female participants between 25 to 75 years of age, inclusive, on the day of Informed Consent signature.
Who cannot join
- Prior participation in clinical trial investigating a huntingtin-lowering therapy (unless participant received only placebo).
- Participants taking medications prohibited by the protocol.
- Any medical history, lumbar surgery or condition that would interfere with the ability to complete the protocol specified assessments.
- Participant has other severe, acute or chronic medical conditions including unstable psychiatric conditions, or laboratory abnormalities that in the opinion of the Investigator may increase the risk associated with study participation, or that may interfere with the interpretation of the study results.
- Any surgical or medical condition which might put the participant at risk in case of participation in the study. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence at the Screening visit.
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
France3 sites
Novartis Investigative Site
Angers, 49933
Novartis Investigative Site
Créteil, 94010
Novartis Investigative Site
Lille, 59037
Germany3 sites
Novartis Investigative Site
Bochum, 44791
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Ulm, 89081
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
Madrid, 28034
Hungary2 sites
Novartis Investigative Site
Budapest, H-1083
Novartis Investigative Site
Szeged, 6720
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Dose Range Finding Study With Open-Label Extension to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of LMI070/Branaplam Administered as Weekly Oral Doses in Participants With Early Manifest Huntington's Disease
This is the first study of branaplam in adults with Huntington's Disease (HD) to determine the correct dose required to lower mutant huntingtin protein (mHTT) levels in the cerebrospinal fluid (CSF) to a degree expected to be efficacious over longer periods of time.
Read the detailed description
This study was a randomized, double-blind, placebo-controlled study with a variable duration (between approximately 17 weeks to approximately 53 weeks) for the core period and a one-year open label extension (OLE) in early-stage manifest Huntington's disease (HD) participants.
After screening period and baseline assessments, the following two Treatment Periods were planned:
- The core period consisted of a 17-week double-blind, placebo-controlled, Dose Range Finding (DRF) portion of the study, followed by a blinded extension (BE) of variable duration (up to approximately 53 weeks). The DRF Period was to evaluate the safety, tolerability, pharmacokinetivs (PK) and pharmacodynamics (PD) of branaplam, as well as determine the optimal dose(s) to explore in further clinical evaluations.
The core period was planned to consist of 3 treatment arms:
- Cohort 1: Treatment Arm A: branaplam 56 mg oral solution or matching placebo, once weekly
- Cohort 2: Treatment Arm B: branaplam 112 mg oral solution or matching placebo, once weekly
- Cohort 3:
Treatment Arm C: branaplam 154 mg oral solution or matching placebo, once weekly or Treatment Arm X: branaplam 84 mg oral solution or matching placebo, once weekly or Treatment Arm Y: branaplam 28 mg oral solution or matching placebo, once weekly
- The OLE was a one-year open-label extension to assess both long-term safety and tolerability, as well as the efficacy of the recommended optimal dose(s) for branaplam.
Due to safety concerns an urgent safety measure (USM) follow-up notification dated 06-Dec-2022 was issued to permanently discontinue the study treatment in all participants. At that point, only cohort 1 was enrolled. Therefore, only cohort 1 data is available for analysis (Treatment Arm A: branaplam 56 mg oral solution or matching placebo, once weekly). Participants who received active treatment (branaplam) were to remain in the study for follow-up for approximately one year following initial treatment discontinuation. The OLE part was not opened.
- Conditions
- Early Manifest Huntington Disease
- Being tested
- Branaplam, Placebo
- Keywords
- Early Manifest, Huntington Disease, Branaplam, LMI070, Dose Range Finding, Safety, HD, mHTT, Pharmacokinetics, oral, Adult
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BranaplamDrug
Also called LMI070
messenger ribonucleic acid (RNA) splicing modifier. Branaplam was administered as an oral solution once weekly.
PlaceboDrug
Matching placebo oral solution once weekly
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A | Experimental | Branaplam 56 mg oral solution once weekly Receives: Drug: Branaplam |
| Treatment Arm B | Experimental | Branaplam 112 mg oral solution once weekly Receives: Drug: Branaplam |
| Treatment Arm C or X or Y | Experimental | (C) Branaplam 154 mg oral solution once weekly, OR (X) Branaplam 84 mg oral solution once weekly OR (Y) Branaplam 28 mg oral solution once weekly Receives: Drug: Branaplam |
| Placebo | Placebo comparator | Matching placebo oral solution once weekly Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change From Baseline to Week 17 in mHTT Protein in CSF
Mutant Huntingtin (mHTT) protein was measured in cerebrospinal fluid (CSF) obtained via lumbar puncture. The percentage change from baseline to Week 17 in mHTT protein in CSF was calculated with the following formula: (mHTTweek17 - mHTTbaseline)/ mHTTbaseline * 100.
Baseline value for mHTT is the last evaluable measurements prior to the first administration of study drug.
Measured: Baseline, Week 17
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs (any AEs regardless of seriousness) and SAEs, including changes in vital signs, neurological examination, electrocardiograms (ECGs) and laboratory parameters qualifying and reported as AEs.
Participants received study treatment up to maximum Week 20 (placebo) and Week 22 (branaplam).
Measured: From first dose of study treatment up to Week 69
Secondary outcomes (20)
Percentage Change From Baseline in Total Brain Volume
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Total Brain Volume Excluding Patients With Subdural Hematoma
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Lateral Ventricles Volume
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Lateral Ventricles Volume Excluding Patients With Subdural Hematoma
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Left Caudate Volume
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Left Caudate Volume Excluding Patients With Subdural Hematoma
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Right Caudate Volume
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Right Caudate Volume Excluding Patients With Subdural Hematoma
Three-dimensional magnetic resonance imaging (MRI) data was acquired and used to measure brain volume at each time point and changes in brain volume longitudinally. Brain MRI scans were performed at each time point without gadolinium contrast.
Changes in volumetric MRI were measured in regions of interests: ventricular, caudate (left and right) and total brain volume.
The baseline MRI scan was obtained within 6 days prior to the first dose of study treatment.
Measured: Baseline, Week 17, Week 33, Week 53, Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Total Functional Capacity (TFC)
The TFC focuses on the investigator's assessment of the participant's capacity to perform a range of activities of daily living. The responses are derived from interview with the participant and/or companion, if applicable. TFC score range from 0 to 13, with higher scores representing better functioning.
Measured: Baseline, Week 17, Week 33 and Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Total Motor Scale (TMS)
The TMS is the cumulative sum of the individual motor ratings obtained during the administration of the motor assessment portion of the UHDRS. TMS score range from 0 to 124 with higher scores representing more significant impairment.
Measured: Baseline, Week 17, Week 33 and Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Independence Scale (IS)
The IS represents the investigator's assessment of the participant's level of independence, including topics of employment, finances, self-care and feeding. The scale has 19 discrete scores, from 10 (tube fed, total bed care) to 100 (no special care needed) with 5-point increments in between.
Measured: Baseline, Week 17, Week 33 and Week 69
Concentrations of mHTT Protein and Total HTT in CSF
Mutant Huntingtin (mHTT) protein and total HTT measured in cerebrospinal fluid (CSF) obtained via lumbar puncture.
Baseline value is the last evaluable measurement prior to the first administration of study drug.
Measured: Baseline, Week 9, Week 17
Concentrations of mHTT Protein and Total HTT in Plasma
Mutant Huntingtin (mHTT) protein and total HTT measured in plasma. Baseline value is the last evaluable measurement prior to the first administration of study drug.
Measured: Baseline, Week 17
Maximum Observed Plasma Concentration (Cmax) of Branaplam and Its Metabolite UFB112
Pharmacokinetic (PK) parameters were calculated based on branaplam and its metabolite UFB112 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Time to Reach Maximum Plasma Concentration (Tmax) of Branaplam and Its Metabolite UFB112
PK parameters were calculated based on branaplam and its metabolite UFB112 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Area Under the Plasma Concentration-time Curve From Time Zero to 168 Hours (AUC0-168h) of Branaplam and Its Metabolite UFB112
PK parameters were calculated based on branaplam and its metabolite UFB112 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-168h calculation.
Measured: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Branaplam and Its Metabolite UFB112
PK parameters were calculated based on branaplam and its metabolite UFB112 plasma concentrations by using non-compartmental methods. The linear trapezoidal method and the regression analysis of the terminal elimination phase were used for AUCinf calculation.
Measured: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1
Trough Concentration (Ctrough) of Branaplam and Its Metabolite UFB112 in Plasma
Branaplam and its metabolite UFB112 concentrations were determined in plasma. Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: pre-dose at Weeks 2, 3, 5, 9, 13 and 17
Trough Concentration (Ctrough) of Branaplam and Its Metabolite UFB112 in CSF
Branaplam and its metabolite UFB112 concentrations were determined in cerebrospinal fluid (CSF) obtained via lumbar puncture. Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: pre-dose at Weeks 9 and 17
Concentration Ratio CSF/Plasma of Branaplam and Its Metabolite UFB112
Branaplam and its metabolite UFB112 concentrations were determined plasma and in cerebrospinal fluid (CSF) obtained via lumbar puncture. Concentration ratios CSF/plasma were calculated for subjects for whom CSF and plasma concentrations were available at the respective time point.
Measured: pre-dose at Weeks 9 and 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start8 Dec 2021
- Primary completion27 Oct 2023
- Study completion27 Oct 2023
Why it stopped: The trial was halted prematurely due to signs and symptoms that suggested the possibility of peripheral neuropathy. All participants who received branaplam continued to undergo routine (safety) evaluations for up to a year following their final dose
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Early Manifest Huntington DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study design used a staggered cohort approach, allowing safety and tolerability of lower doses to be assessed before randomizing subjects to higher doses. At the time of the Cohort Gating Assessments (CGAs), all available data was reviewed from a safety and dose finding perspective by an independent Sponsor team to support the decision to open the next cohort. The independent Data Monitoring Committee (DMC) reviewed the data separately. The decision to open a new cohort was planned to be made by the Sponsor in consultation with the DMC.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05111249
- Sponsor's protocol ID
- CLMI070C12203
- Other IDs
- 2020-000105-92
- Acronym
- VIBRANT-HD
- Status last verified
- May 2025
- First submitted
- 15 Oct 2021
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Publications
Borowsky B, Ramos H, Caputo A, Hartmann A, Faller T, Peters T, Sui Y, Liu F, Meadowcroft M, David OJ, Laisney M, Kinhikar A, Marder KS, Tabrizi SJ, Landwehrmeyer GB, Leavitt BR. Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial. Nat Med. 2026 Jan;32(1):103-112. doi: 10.1038/s41591-025-04117-4. Epub 2026 Jan 5.
PubMed 41491108Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.
PubMed 38489195Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.
PubMed 36463457
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Dose Range Finding Study With Open-Label Extension to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of LMI070/Branaplam Administered as Weekly Oral Doses in Participants With Early Manifest Huntington's Disease
- ClinicalTrials.gov ID
- NCT05111249
- Acronym / sponsor ID
- VIBRANT-HD / CLMI070C12203
- Conditions
- Early Manifest Huntington Disease
- Keywords
- Early Manifest, Huntington Disease, Branaplam, LMI070, Dose Range Finding, Safety, HD, mHTT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was halted prematurely due to signs and symptoms that suggested the possibility of peripheral neuropathy. All participants who received branaplam continued to undergo routine (safety) evaluations for up to a year following their final dose
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Dec 2021 (actual)
- Primary completion
- 27 Oct 2023 (actual)
- Study completion
- 27 Oct 2023 (actual)
- First posted
- 8 Nov 2021 (actual)
- Results
- Posted 4 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is the first study of branaplam in adults with Huntington's Disease (HD) to determine the correct dose required to lower mutant huntingtin protein (mHTT) levels in the cerebrospinal fluid (CSF) to a degree expected to be efficacious over longer periods of time.
Detailed description
This study was a randomized, double-blind, placebo-controlled study with a variable duration (between approximately 17 weeks to approximately 53 weeks) for the core period and a one-year open label extension (OLE) in early-stage manifest Huntington's disease (HD) participants.
After screening period and baseline assessments, the following two Treatment Periods were planned:
- The core period consisted of a 17-week double-blind, placebo-controlled, Dose Range Finding (DRF) portion of the study, followed by a blinded extension (BE) of variable duration (up to approximately 53 weeks). The DRF Period was to evaluate the safety, tolerability, pharmacokinetivs (PK) and pharmacodynamics (PD) of branaplam, as well as determine the optimal dose(s) to explore in further clinical evaluations.
The core period was planned to consist of 3 treatment arms:
- Cohort 1: Treatment Arm A: branaplam 56 mg oral solution or matching placebo, once weekly
- Cohort 2: Treatment Arm B: branaplam 112 mg oral solution or matching placebo, once weekly
- Cohort 3:
Treatment Arm C: branaplam 154 mg oral solution or matching placebo, once weekly or Treatment Arm X: branaplam 84 mg oral solution or matching placebo, once weekly or Treatment Arm Y: branaplam 28 mg oral solution or matching placebo, once weekly
- The OLE was a one-year open-label extension to assess both long-term safety and tolerability, as well as the efficacy of the recommended optimal dose(s) for branaplam.
Due to safety concerns an urgent safety measure (USM) follow-up notification dated 06-Dec-2022 was issued to permanently discontinue the study treatment in all participants. At that point, only cohort 1 was enrolled. Therefore, only cohort 1 data is available for analysis (Treatment Arm A: branaplam 56 mg oral solution or matching placebo, once weekly). Participants who received active treatment (branaplam) were to remain in the study for follow-up for approximately one year following initial treatment discontinuation. The OLE part was not opened.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- The study design used a staggered cohort approach, allowing safety and tolerability of lower doses to be assessed before randomizing subjects to higher doses. At the time of the Cohort Gating Assessments (CGAs), all available data was reviewed from a safety and dose finding perspective by an independent Sponsor team to support the decision to open the next cohort. The independent Data Monitoring Committee (DMC) reviewed the data separately. The decision to open a new cohort was planned to be made by the Sponsor in consultation with the DMC.
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A | Experimental | Drug: BranaplamBranaplam 56 mg oral solution once weekly |
| Treatment Arm B | Experimental | Drug: BranaplamBranaplam 112 mg oral solution once weekly |
| Treatment Arm C or X or Y | Experimental | Drug: Branaplam(C) Branaplam 154 mg oral solution once weekly, OR (X) Branaplam 84 mg oral solution once weekly OR (Y) Branaplam 28 mg oral solution once weekly |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo oral solution once weekly |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Clinically diagnosed Stage 1 or 2 Huntington's disease with a diagnostic confidence level (DCL) = 4 and a United Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) >8 at screening.
- Genetically confirmed Huntington's disease, with presence of ≥40 cytosine-adenineguanine (CAG) repeats in the huntingtin gene.
- Male and female participants between 25 to 75 years of age, inclusive, on the day of Informed Consent signature.
Key exclusion criteria (5 listed)
- Prior participation in clinical trial investigating a huntingtin-lowering therapy (unless participant received only placebo).
- Participants taking medications prohibited by the protocol.
- Any medical history, lumbar surgery or condition that would interfere with the ability to complete the protocol specified assessments.
- Participant has other severe, acute or chronic medical conditions including unstable psychiatric conditions, or laboratory abnormalities that in the opinion of the Investigator may increase the risk associated with study participation, or that may interfere with the interpretation of the study results.
- Any surgical or medical condition which might put the participant at risk in case of participation in the study. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence at the Screening visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BranaplamAlso: LMI070messenger ribonucleic acid (RNA) splicing modifier. Branaplam was administered as an oral solution once weekly. | Drug | Treatment Arm A, Treatment Arm B, Treatment Arm C or X or Y |
| PlaceboMatching placebo oral solution once weekly | Drug | Placebo |
Primary outcome
Percentage Change From Baseline to Week 17 in mHTT Protein in CSF
Time frame: Baseline, Week 17
Mutant Huntingtin (mHTT) protein was measured in cerebrospinal fluid (CSF) obtained via lumbar puncture. The percentage change from baseline to Week 17 in mHTT protein in CSF was calculated with the following formula: (mHTTweek17 - mHTTbaseline)/ mHTTbaseline * 100. Baseline value for mHTT is the last evaluable measurements prior to the first administration of study drug.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study treatment up to Week 69
Incidence of AEs (any AEs regardless of seriousness) and SAEs, including changes in vital signs, neurological examination, electrocardiograms (ECGs) and laboratory parameters qualifying and reported as AEs. Participants received study treatment up to maximum Week 20 (placebo) and Week 22 (branaplam).
20 secondary outcomes
Percentage Change From Baseline in Total Brain Volume
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Total Brain Volume Excluding Patients With Subdural Hematoma
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Lateral Ventricles Volume
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Lateral Ventricles Volume Excluding Patients With Subdural Hematoma
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Left Caudate Volume
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Left Caudate Volume Excluding Patients With Subdural Hematoma
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Right Caudate Volume
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Percentage Change From Baseline in Right Caudate Volume Excluding Patients With Subdural Hematoma
Time frame: Baseline, Week 17, Week 33, Week 53, Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Total Functional Capacity (TFC)
Time frame: Baseline, Week 17, Week 33 and Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Total Motor Scale (TMS)
Time frame: Baseline, Week 17, Week 33 and Week 69
Change From Baseline in the Unified Huntington's Disease Rating Scales (UHDRS) Independence Scale (IS)
Time frame: Baseline, Week 17, Week 33 and Week 69
Concentrations of mHTT Protein and Total HTT in CSF
Time frame: Baseline, Week 9, Week 17
Concentrations of mHTT Protein and Total HTT in Plasma
Time frame: Baseline, Week 17
Maximum Observed Plasma Concentration (Cmax) of Branaplam and Its Metabolite UFB112
Time frame: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Time to Reach Maximum Plasma Concentration (Tmax) of Branaplam and Its Metabolite UFB112
Time frame: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Area Under the Plasma Concentration-time Curve From Time Zero to 168 Hours (AUC0-168h) of Branaplam and Its Metabolite UFB112
Time frame: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1 and Week 17
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Branaplam and Its Metabolite UFB112
Time frame: pre-dose and 4, 7, 12, 22, 72 and 168 hours after branaplam dose at Week 1
Trough Concentration (Ctrough) of Branaplam and Its Metabolite UFB112 in Plasma
Time frame: pre-dose at Weeks 2, 3, 5, 9, 13 and 17
Trough Concentration (Ctrough) of Branaplam and Its Metabolite UFB112 in CSF
Time frame: pre-dose at Weeks 9 and 17
Concentration Ratio CSF/Plasma of Branaplam and Its Metabolite UFB112
Time frame: pre-dose at Weeks 9 and 17
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41491108Borowsky B, Ramos H, Caputo A, Hartmann A, Faller T, Peters T, Sui Y, Liu F, Meadowcroft M, David OJ, Laisney M, Kinhikar A, Marder KS, Tabrizi SJ, Landwehrmeyer GB, Leavitt BR. Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial. Nat Med. 2026 Jan;32(1):103-112. doi: 10.1038/s41591-025-04117-4. Epub 2026 Jan 5.
- Derived from this study: PubMed 38489195Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.
- Derived from this study: PubMed 36463457Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Branaplam in people with Early Manifest Huntington Disease, run by Novartis Pharmaceuticals at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France, Germany, Spain, Hungary, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline to Week 17 in mHTT Protein in CSF (time frame: Baseline, Week 17). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05111249, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.