A Phase 2 interventional study of VX15/2503 and Placebo in Huntington's Disease, sponsored by Vaccinex Inc.. Completed at 32 sites in 2 countries. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2022-05-02.
Sponsored by Vaccinex Inc. · Phase 2, Interventional, and Treatment
The purpose of this study is to evaluate the safety, tolerability, PK, and efficacy of Pepinemab in subjects with late prodromal and early manifest Huntington's disease.
VX15/2503-N-131 (SIGNAL-HD) is a Phase 2, multi-center, randomized, double-blind, placebo controlled study of VX15/2503 (pepinemab) in subjects with late prodromal and early manifest Huntington's disease. The primary objective is to evaluate the safety and tolerability of monthly IV administration of a single dosage of pepinemab (or placebo). Efficacy endpoints include determining the effect of pepinemab on brain volumes (MRI), FDG-PET imaging, 11C-PBR28 (TSPO) PET imaging (subset of Cohort B only) and clinical features of HD including cognition, motor function, behavior, functional abilities, global function and global measurement of change. Additional endpoints include PK / PD, immunogenicity, and exploratory biomarkers. Subjects in Cohort B that have received 12 months of pepinemab who volunteer will undergo a lumbar puncture at V13 to collect cerebral spinal fluid (CSF) to evaluate pepinemab mAb concentrations, total sSEMA4D levels, and other biomarkers in their CSF. Enrollment will involve approximately 276 individuals who are 21 years of age or older with late prodromal (CAG-age product score (CAP score) of greater than 200 and Diagnostic Confidence Level (DCL) of 2 or 3) or early manifest HD (Total Functional Capacity (TFC) greater than or equal to 11). The study will be divided into Cohort A and Cohort B. Cohort A is now complete and an unblinded analysis has been performed. Cohort A subjects were treated for 6 months with either drug or placebo (1:1) and then all subjects were treated with drug for 6 months, followed by 3 months of follow up. Treatment duration for each subject in Cohort A was 12 months. Participation in Cohort A included a Screening visit, a Baseline visit within 30 days of screening; 12 monthly treatment visits beginning at baseline and continuing through Month 12; follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort A subjects participated in the study for approximately 16 months. Based on the analysis of Cohort A, it was decided to extend the duration of treatment for a subset of subjects in Cohort B to evaluate the clinical response to pepinemab after 36 months. Additional enrolled subjects in Cohort B will be treated with drug or placebo (1:1). Participation in Cohort B will include a Screening visit, a Baseline visit within 30 days of screening; 18 or 36 monthly visits beginning at baseline and continuing through Month 18 or Month 36; follow-up safety phone call or visit, and for a subset of subjects, a follow-up safety visit three and six months after the final infusion. Cohort B subjects will participate in the study for approximately 19 and up to 37 months.
293 studies on the registry are indexed under Huntington Disease; 54 are open to participants now.
This study's enrollment of 301 is above the median of 40 across 207 interventional studies indexed under Huntington Disease.
Browse Huntington Disease studies →Vaccinex Inc. is the lead sponsor of 7 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Must fulfill one of the following criteria at Screening:
Must fulfill both of the following criteria at Screening:
Exclusion Criteria Highlights:
Are a suicide risk, as determined by meeting any of the following criteria:
Have any of the following conditions (which would exclude MRI participation):
NOTE: If PET is done on PET-MRI all the above conditions apply for PET-MRI.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study drug VX15/2503 will be administered via monthly intravenous infusions
Drug: VX15/2503
A placebo control will be administered via monthly intravenous infusions
Drug: Placebo
Drug page: Pepinemab
VX15/2503 (pepinemab) is a humanized IgG4 monoclonal antibody and will be administered intravenously at a dose of 20 mg/kg. The antibody is formulated at 20 mg/mL in 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80.
Also known as: pepinemab
Placebo consists of formulation buffer only which is 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80.
Revisions to SAP were made prior to un-blinding, on June 30, 2020, upon consultation with FDA.
If primary outcome, listed below (Outcome 3), does not reach its critical p-value, the secondary outcomes will not be formally tested. If both co-primary outcomes are statistically significant, the five secondary outcomes will be formally tested following a hierarchical testing procedure.
Time frame: Prior to DBL/Study Completion
Safety and tolerability of monthly intravenous (IV) administration of pepinemab relative to placebo in subjects with early HD (Cohort B pooled, includes Cohort B1 Early Manifest and Cohort B2 Late Prodromal HD).
Measured by drug related adverse event frequency and laboratory test abnormalities in all subjects.
Time frame: Up to 18 months
Efficacy of monthly IV administration of pepinemab relative to placebo in Early Manifest HD (Cohort B1)
Co-primary outcome measured by the change from baseline in the Huntington's Disease Two-item Cognitive Family (PTAP and OTS) selected from the Huntington's Disease
Time frame: Up to 18 months
Clinical feature of Early Manifest HD: motor function (Q-Motor)
Measured by change from baseline of Q-Motor Tap Speed IOI duration mean in Cohort B1
Time frame: Up to 18 months
Clinical feature of Early Manifest HD: functional capacity (UHDRS-TFC)
Measured by change from baseline of UHDRS-TFC score in Cohort B1
Time frame: Up to 18 months
Clinical feature of Early HD: functional capacity (UHDRS-TFC)
Measured by time to 1-point change in UHDRS-TFC score in Cohort B pooled
Time frame: Up to 18 months
Clinical Feature of Early HD: motor function (Q-Motor)
Measured by change from baseline of Q-Motor Tap Speed IOI duration mean in Cohort B pooled
Time frame: Up to 18 months
Clinical Feature of Early HD: cognition (Huntington's Disease Two-item Cognitive Family).
Measured by change from baseline in the two-item HD-CAB family (PTAP and OTS) in Cohort B pooled
Time frame: Up to 18 months
Clinical feature of HD: cognition
Measured by change from baseline in the HD-CAB composite score
Time frame: Up to 18 months
Impact of monthly IV administration of pepinemab relative to placebo on change in brain metabolic activity
Measured by change from baseline \[18F\]-Fluoro-2-Deoxy-D-Glucose positron emission tomography (FDG-PET) standardized uptake value ratio (SUVR) Cortical Composite Index averaging results over the right and left sides of the brain in a subset of both late prodromal and early manifest subjects
Time frame: Up to 18 months
Impact of monthly IV administration of pepinemab relative to placebo on change in brain volume
Measured by change from baseline in volumetric magnetic resonance imaging (MRI) averaging results over the right and left sides of the brain (BBSI, CBSI, VBSI, and change in white matter)
Time frame: Up to 18 months
Brain metabolic activity
Measured by change from baseline in \[11C\]-PBR28 translocator protein positron emission tomography (TSPO-PET) in a small subset of late prodromal subjects (Cohort B2)
Time frame: Up to 18 months
pepinemab and total sSEMA4D levels in cerebral spinal fluid (CSF)
PK parameter
Time frame: Up to 18 months
Immunogenicity of monthly IV administration of pepinemab relative to placebo
Measured by the frequency and titer of anti-drug antibodies and human anti-human antibodies
Time frame: Up to 18 months
Immunophenotyping of monthly IV administration of pepinemab relative to placebo
Measured by the levels of peripheral immune subsets in whole blood, including such lymphocyte subsets as B cells, T cells, and NK cells
Time frame: Up to 18 months
Peak serum concentration (Cmax) of monthly IV administration of pepinemab
PK parameter
Time frame: Up to 18 months
Area under the serum concentration versus time curve (AUC) of monthly IV administration of pepinemab
PK parameter
Time frame: Up to 18 months
Half-life of VX15/2503 of monthly IV administration of pepinemab
PK parameter
Time frame: Up to 18 months
SEMA4D saturation in whole blood of monthly IV administration of pepinemab
PD parameter to determine T-cell receptor occupancy
Time frame: Up to 18 months
T-cell SEMA4D levels in whole blood of monthly IV administration of pepinemab
PD parameter
Time frame: Up to 18 months
Total soluble SEMA4D levels in serum of monthly IV administration of pepinemab
PD parameter to determine the levels of total soluble SEMA4D
Time frame: Up to 18 months
Clinical feature of HD: functional abilities
Measured by change from baseline in UHDRS core functional assessments
Time frame: Up to 18 months
Clinical Feature of HD: Patient Reported Outcome
Measured by the overall response to therapy using patient reported impression of change (PGIC)
Time frame: Up to 18 months
Clinical feature of HD: behavior
Measured by change from baseline in the Problem Behavioral Assessment-Short (PBA) questionnaire
Time frame: Up to 18 months
Clinical feature of HD: Patient Reported Outcome
Measured by change from baseline in the Huntington Disease Health Index (HD-HI) Index
Time frame: Up to 18 months
Clinical Safety and Non-Safety Laboratory Assessments (Clinical, Imaging, PK, PD and/or Immunogenicity)
Dataset analysis
Time frame: Up to 36 months
The record gives a start of Jul 2015, a primary completion of Aug 2020 and a completion of Aug 2020. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pepinemab
Vaccinex Inc.