ArticleNeurology(R) neuroimmunology & neuroinflammation2017
Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study Of The Safety, Tolerability, And Pharmacokinetics Of Intravenous VX15/2503 In Patients With Multiple Sclerosis
SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD): A Multi-center, Randomized, Double-Blind, Placebo-Controlled Safety and Biomarker Study of Pepinemab Anti-SEMA4D Antibody in Early-AD
A Phase 1b/2 Study of the Combination of Pepinemab and Pembrolizumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Who cites it
34 citing papers in PubMed.
- A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614).Pediatric blood & cancer · 2024Trial
- Pepinemab antibody blockade of SEMA4D in early Huntington's disease: a randomized, placebo-controlled, phase 2 trial.Nature medicine · 2022Trial
- Semaphorins and Their Role in Neuropathic Pain.Life (Basel, Switzerland) · 2026Review
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Research Advances in the Immunomodulatory Functions of CD100/SEMA4D and Their Roles in Viral Infectious Diseases.International journal of molecular sciences · 2025Review
- Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes.Nature communications · 2025Article
- Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.Archives of pharmacal research · 2024Review
- Remyelination in animal models of multiple sclerosis: finding the elusive grail of regeneration.Frontiers in molecular neuroscience · 2023Review
- Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?Frontiers in pharmacology · 2023Review
- Semaphorin 4D is upregulated in neurons of diseased brains and triggers astrocyte reactivity.Journal of neuroinflammation · 2022Article
- Current and Possible Future Therapeutic Options for Huntington's Disease.Journal of central nervous system disease · 2022Review
- Unraveling Axon Guidance during Axotomy and Regeneration.International journal of molecular sciences · 2021Review
- Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis.Journal of internal medicine · 2021Review
- Review
- Review
- Interaction between Neurons and the Oligodendroglial Lineage in Multiple Sclerosis and Its Preclinical Models.Life (Basel, Switzerland) · 2021Review
- Huntington's Disease: New Frontiers in Therapeutics.Current neurology and neuroscience reports · 2021Review
- Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Semaphorins in Adult Nervous System Plasticity and Disease.Frontiers in synaptic neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VX15/2503 in a randomized, single-dose, dose-escalation, double-blind, placebo-controlled study enrolling adult patients with MS.
methodsSingle IV doses of VX15/2503 or placebo were administered. Ten patients each were randomized (4:1 randomization ratio) into 5 ascending dose cohorts of 1, 3, 6, 10, or 20 mg/kg. Safety, immunogenicity, PK/PD, MRI, ECG, and lymphocyte subset levels were evaluated. A Dose Escalation Safety Committee (DESC) approved each dose escalation.
resultsVX15/2503 was well tolerated, and all participants completed the study. Antibody treatment-related adverse events were primarily grade 1 or 2 and included urinary tract infection (12.5%) and muscle weakness, contusion, and insomnia (each 7.5%). No dose-limiting toxicities were observed, and no maximum tolerated dose was determined. One subject (20 mg/kg) experienced disease relapse 3 months before study entry and exhibited a grade 3 (nonserious) increase in brain lesions by day 29, possibly related to VX15/2503. Twenty-nine patients exhibited human anti-humanized antibody responses; 5 with titer ≥100. No anti-VX15/2503 antibody responses were fully neutralizing. VX15/2503 C
conclusionsThese results support the continued investigation of VX15/2503 in neurodegenerative diseases. CLINICALTRIALSGOV IDENTIFIER: NCT01764737. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anti-semaphorin 4D antibody VX15/2503 at various doses was safe and well tolerated vs placebo, although an increase in treatment-emergent adverse events in the treatment group could not be excluded (risk difference -0.7%, 95% CI -28.0% to 32.7%).
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.