Trial reportOrphanet journal of rare diseases2016
Combined integrated protocol/basket trial design for a first-in-human trial.
Trial report in Orphanet journal of rare diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Basket trials in rare diseases: a systematic review of current practices, methodological challenges, and future directions.Orphanet journal of rare diseases · 2025Pooled it
- Interventions for bullous pemphigoid.The Cochrane database of systematic reviews · 2023Pooled it
- Trial
- A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway.Clinical pharmacology and therapeutics · 2018Trial
- Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera From Subjects Dosed With the Anti-C1s Monoclonal Antibody TNT009-Results from a Randomized First-in-Human Phase 1 Trial.Transplantation · 2017Trial
- Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab.Journal of medical virology · 2024Article
- Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.BMC medicine · 2023Review
- Application of Bayesian methods to accelerate rare disease drug development: scopes and hurdles.Orphanet journal of rare diseases · 2022Review
- Sutimlimab: First Approval.Drugs · 2022Review
- A State-of-the-Art Roadmap for Biomarker-Driven Drug Development in the Era of Personalized Therapies.Journal of personalized medicine · 2022Review
- Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways.The Journal of investigative dermatology · 2022Review
- Innovative highlights of clinical drug trial design.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Reporting of master protocols towards a standardized approach: A systematic review.Contemporary clinical trials communications · 2019Article
- Complement System in Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2019Review
- C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Analysis of integrated clinical trial protocols in early phases of medicinal product development.European journal of clinical pharmacology · 2017Article
- Effect of the Anti-C1s Humanized Antibody TNT009 and Its Parental Mouse Variant TNT003 on HLA Antibody-Induced Complement Activation-A Preclinical In Vitro Study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Drugs for rare disorders.British journal of clinical pharmacology · 2017Article
- From promising molecules to orphan drugs: Early clinical drug development.Intractable & rare diseases research · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInnovative trial designs are sought to streamline drug development in rare diseases. Basket- and integrated protocol designs are two of these new strategies and have been applied in a handful oncologic trials. We have taken the concept outside the realm of oncology and report about a first-in-human integrated protocol design that facilitates the transition from phase Ia in healthy volunteers to phase Ib in patients with rare complement-mediated disorders driven by the classical pathway.
resultsWe have been conducting a prospective, double-blind, randomized, placebo-controlled first-in-human study with TNT009, which is a humanized monoclonal antibody directed against the C1s subunit of human complement component C1. The trial consisted of three subparts, including normal healthy volunteers (part one and two) and a single cohort of patients in part three. Patients suffered from various complement-mediated diseases sharing the same pathophysiological mechanism, i.e. bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune hemolytic anemia. Primary objective of the trial has been to evaluate the safety and tolerability of TNT009 in humans.
conclusionsThis trial provides probably the first example that basket trials may not be limited to single genetic aberrations, which is overly restrictive, but our trial design demonstrates that pathway specificity is a viable paradigm for defining baskets. This will hopefully serve as a role model that could benefit other innovative drug development programs targeting rare diseases.
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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.