Investigation of the Delve Detect Cerebrospinal Fluid (CSF) Metagenomic Next-generation Sequencing (mNGS) Test When Used for the Initial Diagnostic Workup of Patients With Suspected Central Nervous System (CNS) Infection

NCT07435649 | Not Yet Recruiting

• 1 other identifier: CLN-GEN-PLN-004
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

Brief Summary

Delve Bio, Inc. is a developer of novel mNGS tests with the goal of aiding in the diagnosis of infectious diseases in several clinical indications that may not have alternative traditional diagnostic methods routinely available. A proof of concept for the clinical utility of this mNGS testing methodology has been described in several seminal publications.1,2,3,4 Delve Bio is currently offering one of these assays as a laboratory-developed test (LDT) performed in a CLIA-certified, CAP-accredited laboratory. The test is called Delve Detect CSF. Delve Detect CSF is an mNGS in vitro diagnostic test intended for the simultaneous detection and differentiation of nucleic acids from multiple bacteria, viruses, fungi, and parasites in CSF from individuals suspected of meningitis or encephalitis. Delve Detect CSF identifies microbial nucleic acid in an unbiased and pathogen-agnostic manner. Historically, due to its cost and turnaround times, which can be on the order of 14 days, CSF mNGS testing is typically employed as a "test of last resort" for patients with suspected infectious meningitis and encephalitis, and is often used when traditional diagnostic methods cannot identify the cause of infection. In the IMPACT Study, we seek to investigate the diagnostic and clinical utility of mNGS testing if it is employed earlier in the diagnostic workup of patients with suspected CNS infection and unknown etiology in conjunction with a more rapid turnaround time for test results on the order of two business days from sample receipt by the laboratory. Participants who meet the inclusion/exclusion criteria and undergo informed consent (and assent as applicable) will be enrolled in the study, assigned to the appropriate subpopulation category, and obtain CSF testing with Delve Detect CSF in addition to other SOC testing. In addition to the Delve Detect CSF test results, associated clinical information and health economic data for the participants will be obtained through chart abstraction. Clinical information will be de-identified wherever possible, and any PHI being collected will not be individually reported as part of the intended analysis. The site investigator or their designee at each site will complete a survey to provide a consensus view of the treatment team regarding how the availability of Delve Detect CSF test results in early diagnostic workup affected clinical decision-making. Analyses of the test results from Delve Detect CSF and other SOC diagnostic methods, in addition to the clinical information, will not be used to identify any participant. Information generated through the study will be recorded in such a manner that the identity of the human participants cannot readily be ascertained directly or through identifiers linked to the participants, and the participants will not be contacted. The results from this study could be used to support publications in scientific white papers, manuscripts, posters, and/or presentations.

Conditions

Central Nervous System Infection

Keywords

Delve Bio; IMPACT Study; mNGS; Central Nervous System (CNS) Infection

Outcome Measures

Primary Outcomes (1)

• Overall Diagnostic Yield

  The primary endpoint of the study is to investigate the utility of Delve Detect CSF with respect to the overall diagnostic yield compared to SOC diagnostic testing.

  From Enrollment to 90 Days Post-Discharge for Each Patient

Study Arms (2)

Prospectively Collected Patients tested with Delve Detect mNGS

EXPERIMENTAL

Participants will be identified as candidates for the prospective enrollment population by clinicians who are treating the patients and/or laboratory investigators performing clinical testing on initial samples obtained from the patients through inpatient or ICU admission. Patients may be identified and enrolled in the study prior to or after CSF collection has been performed. Following informed consent and assent procedures, as applicable, participants will be enrolled in the study. Following enrollment and informed consent/assent, 500 - 1000 µL of CSF specimen collected as part of the first LP for SOC diagnostic workup will be sent for mNGS testing with the Delve Detect CSF test. Delve Detect CSF test results will be provided to treating physicians for clinical decision-making.

Diagnostic Test: Delve Detect CSF mNGS Test

Real-World Data Control Cohort

ACTIVE COMPARATOR

RWD will be used to construct a control dataset for patients who were diagnosed and treated without the use of CSF mNGS. An attempt will be made to match the calendar time period/duration, and proportions of sex, age, disease, etiology (infectious/non-infectious), and subpopulation categories as the prospective enrollment population. The intent of the control population is to enable secondary and exploratory outcome comparisons by collecting data for patients who were diagnosed and treated without the use of CSF mNGS testing.

Other: Real-World Data

Interventions

Delve Detect CSF mNGS Test DIAGNOSTIC_TEST

This cohort consists of patients admitted with suspected CNS infection, who will receive Delve Detect CSF mNGS testing from a prospectively collected CSF specimen. The results of the Delve Detect CSF mNGS Test will be returned to the patient's treatment team for clinical decision making.

Prospectively Collected Patients tested with Delve Detect mNGS

Real-World Data OTHER

For the analysis of secondary and exploratory outcomes, a control population of patients who were diagnosed and treated without the use of CSF mNGS testing will be constructed using real-world data (RWD). The control population will have approximately equal proportions of demographics, disease severity, and subpopulation categories as the prospective enrollment population. RWD will be used to examine the potential effect that testing with Delve Detect CSF had on the selected outcomes with the prospectively enrolled participants by collecting data for patients who were diagnosed and treated without the use of CSF mNGS testing. These participants will be enrolled in the non-mNGS control population and have de-identified RWD collected through a waiver of informed consent as appropriate for comparison to the prospective enrollment population.

Real-World Data Control Cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be willing and able to provide informed consent or have a legally authorized representative (LAR) willing and able to provide informed consent for participation in the study:
• a. Adults, 18 years of age or older, must provide informed consent, or if unable to provide consent, must have voluntary informed consent provided by a LAR b. Children \< 18 years of age must have informed consent provided by a parent, guardian, or LAR, and: i. If 7 years of age or older, must provide voluntary assent for participation, unless unable to do so If less than 7 years of age, assent should also be obtained, if feasible.
• Individuals presenting with, or admitted or transferred with, suspected CNS infection with at least 2 of the following clinical signs and symptoms:
• Headache
• Photophobia
• Neck stiffness
• Nausea/vomiting
• Documented fever ≥ 38°C (100.4°F)
• Altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥ 24 h with no alternative cause identified
• Generalized or partial seizures not fully attributable to a preexisting seizure disorder, identified toxic-metabolic derangement, or alcohol withdrawal
• Abnormality of brain parenchyma on neuroimaging suggestive of CNS infection that is either new from prior studies or appears acute in onset
• Abnormal spinal cord imaging suggestive of myelitis
• Note: The clinical signs and symptoms list above applies to non-infant participants (≥ 1 year old). Infants (\< 1 year old) who are suspected of CNS infection may be enrolled if they present with fever ≥ 38°C (100.4°F) OR hypothermia \< 36.5°C (97.7°F) AND at least 1 of the following clinical signs and symptoms:
• Bulging fontanel (soft spot)
• Lethargy or irritability

Sponsors & Collaborators

• Delve Bio, Inc.: lead

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (4)

• Benoit P, Brazer N, de Lorenzi-Tognon M, Kelly E, Servellita V, Oseguera M, Nguyen J, Tang J, Omura C, Streithorst J, Hillberg M, Ingebrigtsen D, Zorn K, Wilson MR, Blicharz T, Wong AP, O'Donovan B, Murray B, Miller S, Chiu CY. Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections. Nat Med. 2024 Dec;30(12):3522-3533. doi: 10.1038/s41591-024-03275-1. Epub 2024 Nov 12.

  PMID: 39533109 BACKGROUND

• Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis. N Engl J Med. 2019 Jun 13;380(24):2327-2340. doi: 10.1056/NEJMoa1803396.

  PMID: 31189036 BACKGROUND

• Miller S, Naccache SN, Samayoa E, Messacar K, Arevalo S, Federman S, Stryke D, Pham E, Fung B, Bolosky WJ, Ingebrigtsen D, Lorizio W, Paff SM, Leake JA, Pesano R, DeBiasi R, Dominguez S, Chiu CY. Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid. Genome Res. 2019 May;29(5):831-842. doi: 10.1101/gr.238170.118. Epub 2019 Apr 16.

  PMID: 30992304 BACKGROUND

• Wilson MR,Naccache SN,Samayoa E,Biagtan M,Bashir H,Yu G,Salamat SM,Somasekar S,Federman S,Miller S,Sokolic R,Garabedian E,Candotti F,Buckley RH,Reed KD,Meyer TL,Seroogy CM,Galloway R,Henderson SL,Gern JE,DeRisi JL,Chiu CY

  BACKGROUND

MeSH Terms

Conditions

Central Nervous System Infections; Infections

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Steve Miller, M.D., Ph.D.

  Delve Bio, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steve Miller, M.D., Ph.D.

CONTACT

844-221-7423; steve.miller@delve.bio

Timothy Blicharz, Ph.D.

CONTACT

tim.blicharz@delve.bio

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 400 participants will be enrolled in the prospective cohort. For the analysis of secondary and exploratory outcomes, a synthetic control population of patients who were treated without the use of CSF mNGS will be constructed using real-world data (RWD) to examine the potential effect that testing with Delve Detect CSF has on the selected outcomes with the prospectively enrolled participants.

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 27, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (2)