Overview

This trial is active, not recruiting.

Condition huntington's disease
Treatments vx15/2503, placebo
Phase phase 2
Sponsor Vaccinex Inc.
Collaborator Huntington Study Group
Start date July 2015
End date June 2018
Trial size 89 participants
Trial identifier NCT02481674, VX15/2503-N-131

Summary

The purpose of this study is to evaluate the safety, tolerability, PK, and efficacy of VX15/2503 in subjects with late prodromal and early manifest Huntington's disease.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
The study drug VX15/2503 will be administered via monthly intravenous infusions
vx15/2503
VX15/2503 is a humanized IgG4 monoclonal antibody and will be dosed intravenously at 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.
(Placebo Comparator)
A placebo control will be administered via monthly intravenous infusions
placebo
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.

Primary Outcomes

Measure
Safety and tolerability as measured by drug related adverse event frequency and laboratory test abnormalities
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B

Secondary Outcomes

Measure
Immunogenicity of VX15/2503 as measured by the frequency and titer of anti-drug antibodies
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Brain volumes measured by MRI and FDG-PET Imaging
time frame: Up to 12 months for cohort A and up to 18 months in Cohort B
Brain inflammation measured by TSPO-PET Imaging
time frame: Up to 18 months in Cohort B
Clinical feature of HD: cognition (HD-CAB)
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Clinical feature of HD: motor function (UHDRS-Motor, Q-Motor)
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Clinical feature of HD: behavior
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Clinical feature of HD: functional abilities
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Peak plasma concentration (Cmax)
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Area under the plasma concentration versus time curve (AUC)
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Half-life of VX15/2503
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
T-cell SEMA4D saturation
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Total sSEMA4D levels
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B
Serum cytokine levels
time frame: Up to 15 months for cohort A and up to 21 months in Cohort B

Eligibility Criteria

Male or female participants at least 21 years old.

Inclusion Criteria Highlights: 1. Male or female and are at least greater than or equal to 21 years of age at Screening. 2. Must fulfill one of the following criteria at Screening: 1. Late prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3, 2. 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. 3. Must fulfill both of the following criteria at Screening: 1. Have undergone genetic testing with a known CAG repeat greater than or equal to 36, 2. No features of juvenile HD (Westphal variant). 4. 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. 5. If male must agree to use a reliable method of birth control. 6. Are willing and capable of providing informed consent for study participation, CAG genotyping (all subjects), and TSPO genotyping (Cohort B only, subset of subjects). 7. Are capable of reading, writing, and communicating effectively with others. 8. Are taking stable doses of any concomitant medications (including tetrabenazine) during the 1 month prior to the Baseline Visit and dosing must remain stable during the duration of the study. 9. Must meet all criteria required for the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer. Exclusion Criteria Highlights: 1. 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. 2. Have had previous neurosurgery for HD or other movement disorders. 3. Are a suicide risk. 4. Have marked cognitive impairment with a Montreal Cognitive Assessment (MoCA) Score less than or equal to 22. 5. Have a presence of clinically significant psychosis and/or confusional states 6. Have clinically significant laboratory or ECG abnormalities at Screening 7. Have clinically relevant hematologic, hepatic, cardiac, or renal disease. 8. Have a medical history of infection with human immunodeficiency virus, hepatitis C, and/or hepatitis B. 9. Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening. 10. If female are pregnant or breastfeeding. 11. Have a known allergy to any ingredient in the study drug. 12. 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. 13. Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the investigator makes the subject unsuitable for the study. 14. Have any significant findings not related to HD on the screening MRI which in the judgment of the investigator makes the subject unsuitable for the study. 15. Have any of the following conditions (which would exclude MRI participation): 1. An implant/device/condition that is contraindicated for MRI 2. Weight above 158 kg 3. Body habitus that would impede completion of MRI scan 16. Are undergoing FDG-PET or TSPO-PET and have any of the following conditions: 1. Have received research-related radiation exposure that exceeds institutional guidelines (e.g., 50 mSv in the prior year), if applicable

Additional Information

Official title A Phase 2, Multi-center, Randomized, Double-blind, Placebo Controlled Study in Subjects With Late Prodromal and Early Manifest Huntington's Disease (HD) to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of VX15/2503
Principal investigator Andrew Feigin, MD
Description VX15/2503-N-131 is a Phase 2, multi-center, randomized, double-blind, placebo controlled study of VX15/2503 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 VX15/2503 (or placebo). Secondary objectives include determining the effect of VX15/2503 on brain volumes (MRI), FDG-PET imaging, 11C-PBR28 (TSPO) PET imaging (Cohort B only) and clinical features of HD including cognition, motor function, behavior, functional abilities, and global function. Additional secondary objectives include PK / PD, immunogenicity, and exploratory biomarkers. Enrollment will involve approximately 94 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 subjects will be treated for 6 months with either drug or placebo (1:1) and then all subjects will be treated with drug for 6 months, followed by 3 months of follow up. Treatment duration for each subject will be 12 months. Participation in Cohort A will include 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 will participate in the study for approximately 16 months. Cohort B subjects will be treated with drug or placebo (1:1) for 18 months, followed by 3 months of follow up. Treatment duration for each subject will be 18 months. Participation in Cohort B will include a Screening visit, a Baseline visit within 30 days of screening; 18 monthly treatment visits beginning at baseline and continuing through Month 18; follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort B subjects will participate in the study for approximately 22 months.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Vaccinex Inc..