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Huntington's DiseasePhase 2SIGNAL-HDNCT02481674

A Study in Subjects With Late Prodromal & Early Manifest HD to Assess the Safety, Tolerability, pk, and Efficacy of Pepi

A Phase 2 study testing VX15/2503 in people with Huntington's Disease, run by Vaccinex Inc. at 32 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Huntington's Disease
What is being tested?
VX15/2503
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
301 participants
Where
32 sitesin 2 countries
Study dates
Jul 2015to Aug 2020
Phase
Phase 2
Are there results?
None posted in the registry

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 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female and are at least greater than or equal to 21 years of age at Screening.
  • Must fulfill one of the following criteria at Screening:
  • Late prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3.
  • Early manifest HD as defined by a TFC greater than or equal to 11. Subject must have been determined to have a clinical diagnosis of HD by the Site Investigator as defined by a DCL of 4.
  • Must fulfill both of the following criteria at Screening:
  • Have undergone genetic testing with a known CAG repeat greater than or equal to 36.
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  • No features of juvenile HD (Westphal variant).
  • If female must be either surgically sterile, postmenopausal, or nonlactating and nonpregnant. Female subjects of childbearing potential must practice a highly effective method of contraception.
  • If male, must agree to use a reliable method of birth control (condoms with contraceptive foams or sexual abstinence) during the study and for 6 months after the last dose of study drug.
  • Are willing and capable of providing informed consent for study participation, CAG genotyping (all subjects).
  • Are capable of reading, writing, and communicating effectively with others.
  • Are taking stable doses of any concomitant medications (including tetrabenazine and deutetrabenazine) during the 1 month prior to the Baseline Visit, with the exception of newly prescribed anxiolytics for the use of pre-medication prior to imaging at screening, which will be permitted on a case-by-case basis.
  • Must meet all criteria required to move forward with the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer.

Who cannot join

  • Have participated in an investigational drug or device study within 30 days of the Baseline Visit, or 180 days if previous investigational drug was a MAb therapeutic, or previously participated in SIGNAL Cohort A. This does not apply to Cohort B subjects who are being offered the option to participate in the extension of Cohort B.
  • Have had previous neurosurgery for Huntington's disease or other movement disorders.
  • Are a suicide risk, as determined by meeting any of the following criteria:
  • suicide attempt within one year prior to Baseline.
  • suicidal ideation as defined by a positive response to question 5 on the C-SSRS (Baseline visit form) suicidal ideation section, within 60 days of the Baseline Visit.
  • significant risk of suicide, as judged by the site Investigator.
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  • Have marked cognitive impairment with a Montreal Cognitive Assessment (MoCA) Score less than or equal to 22.
  • Have a presence of clinically significant psychosis and/or confusional states, in the opinion of the site Investigator.
  • Have clinically significant laboratory or ECG abnormalities at Screening, in the opinion of the site Investigator.
  • Have clinically relevant hematologic, hepatic, cardiac, or renal disease.
  • Have a medical history of infection with human immunodeficiency virus, hepatitis C and/or hepatitis B, or found to have an abnormality at Screening.
  • Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening.
  • If female are pregnant or breastfeeding.
  • Have a known allergy to any ingredient in the study drug.
  • Have a history of malignancy of any type within 2 years prior to Screening. A history of surgically excised non-melanoma skin cancers, and superficial bladder or prostate cancer is permitted.
  • Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the site Investigator makes the subject unsuitable for the study.
  • Have any significant findings not related to HD on the screening MRI which in the judgment of the site Investigator makes the subject unsuitable for the study.
  • Have any of the following conditions (which would exclude MRI participation):
  • An implant/device/condition that is contraindicated for MRI (e.g. pacemaker, severe claustrophobia, prosthetic heart valve, any metal fragments in the eyes or body--in some cases, an X-ray may be needed before an MRI scan, to ensure it is safe to enter the scanner).
  • Body habitus that would impede completion of MRI scan. (Subject weight above 158 kg should be discussed with the Medical Monitor).
  • NOTE: If PET is done on PET-MRI all the above conditions apply for PET-MRI.
  • Are undergoing FDG-PET and have received research-related radiation exposure that exceeds institutional guidelines in the prior year if applicable.
  • Are undergoing a LP for CSF collection and have any of the following conditions: uncorrected bleeding or clotting disorders, skin infections near the site of the LP, suspicion of increased intracranial pressure, allergies to numbing medications (local anesthetics), acute spinal trauma, history of migraines.
  • Are undergoing a LP for CSF collection and taking any of the following types of anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, or thrombin inhibitors.

Trial locations and contacts

32 sites in 2 countries.

32 sites in 2 countries

United States29 sites

  • University of Michigan

    Ann Arbor, Michigan, 48105

  • Emory University School of Medicine

    Atlanta, Georgia, 30329

  • University of Colorado - Denver

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21218

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • University of Vermont

    Burlington, Vermont, 05401

  • Massachusetts General Hospital

    Charlestown, Massachusetts, 02129

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Ohio State University

    Columbus, Ohio, 43210

  • Duke University Health Center

    Durham, North Carolina, 27705

  • University of Florida Gainesville

    Gainesville, Florida, 32611

  • University of Texas Houston Medical School

    Houston, Texas, 77030

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of California, San Diego

    La Jolla, California, 92037

  • University of Louisville

    Louisville, Kentucky, 40202

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Columbia University

    New York, New York, 10027

  • Columbia University

    New York, New York, 10032

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of Rochester

    Rochester, New York, 14618

  • University of California San Francisco

    San Francisco, California, 94143

  • University of Washington and VA Puget Sound Health Care System

    Seattle, Washington, 98195

  • University of Washington

    Seattle, Washington, 98195

  • Washington University

    St Louis, Missouri, 63110

  • University of Toledo

    Toledo, Ohio, 43614

  • Georgetown University

    Washington D.C., District of Columbia, 20007

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada3 sites

  • University of Alberta

    Edmonton, Alberta, T6G 2R3

  • Centre hospitalier de l'Université de Montréal (CHUM)

    Montreal, Quebec, H2X 0C1

  • University of British Columbia

    Vancouver, British Columbia, V6T 1Z4

Other trials in Canada

About this study

Official title: A Phase 2, Multi-center, Randomized, Double-blind, Placebo Controlled Study in Subjects With Late Prodromal and Early Manifest Huntington's Disease to Assess the Safety, Tolerability, pk, and Efficacy of Pepinemab

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.

Read the detailed description

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.

Being tested
VX15/2503, Placebo
Keywords
Prodromal Stage, Early Manifest Stage
Medical subject headings
Huntington Disease, Prodromal Symptoms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VX15/2503Drug

    Also called 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.

  • PlaceboDrug

    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.

Study groups in NCT02481674
Study groupRoleWhat they receive
VX15/2503ExperimentalThe study drug VX15/2503 will be administered via monthly intravenous infusions
Receives: Drug: VX15/2503
PlaceboPlacebo comparatorA placebo control will be administered via monthly intravenous infusions
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Prior to DBL/Study Completion

  2. 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.

    Measured: Up to 18 months

  3. 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

    Measured: Up to 18 months

Secondary outcomes (5)

  1. 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

    Measured: Up to 18 months

  2. Clinical feature of Early Manifest HD: functional capacity (UHDRS-TFC)

    Measured by change from baseline of UHDRS-TFC score in Cohort B1

    Measured: Up to 18 months

  3. Clinical feature of Early HD: functional capacity (UHDRS-TFC)

    Measured by time to 1-point change in UHDRS-TFC score in Cohort B pooled

    Measured: Up to 18 months

  4. 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

    Measured: Up to 18 months

  5. 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

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2015 (estimated)
  2. Study startJul 2015
  3. Primary completionAug 2020
  4. Study completionAug 2020

Resources

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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
301 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02481674
Sponsor's protocol ID
VX15/2503-N-131
Acronym
SIGNAL-HD
Status last verified
Apr 2022
First submitted
19 Jun 2015
Last updated
2 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Southwell AL, Franciosi S, Villanueva EB, Xie Y, Winter LA, Veeraraghavan J, Jonason A, Felczak B, Zhang W, Kovalik V, Waltl S, Hall G, Pouladi MA, Smith ES, Bowers WJ, Zauderer M, Hayden MR. Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease. Neurobiol Dis. 2015 Apr;76:46-56. doi: 10.1016/j.nbd.2015.01.002. Epub 2015 Feb 3.

    PubMed 25662335

  • Estevez-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

  • Feigin A, Evans EE, Fisher TL, Leonard JE, Smith ES, Reader A, Mishra V, Manber R, Walters KA, Kowarski L, Oakes D, Siemers E, Kieburtz KD, Zauderer M; Huntington Study Group SIGNAL investigators. Pepinemab antibody blockade of SEMA4D in early Huntington's disease: a randomized, placebo-controlled, phase 2 trial. Nat Med. 2022 Oct;28(10):2183-2193. doi: 10.1038/s41591-022-01919-8. Epub 2022 Aug 8.

    PubMed 35941373

  • Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: August 2018. J Huntingtons Dis. 2018;7(3):279-286. doi: 10.3233/JHD-189003.

    PubMed 30103342

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX15/2503 in people with Huntington's Disease, run by Vaccinex Inc. at 32 sites in 2 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 13 inclusion and 24 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: finished, as of the sponsor's last update on 2 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Revisions to SAP were made prior to un-blinding, on June 30, 2020, upon consultation with FDA. (time frame: Prior to DBL/Study Completion). The study lists 3 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 NCT02481674, which also lists 4 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 2 May 2022.

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