The first patient in Enanta Pharmaceuticals’ RESOLVE Phase 2b/3 study was dosed on October 26, 2026. That sentence reads like a routine milestone announcement. To a site director managing high-risk adult outpatient capacity this RSV season, it reads like a countdown clock that just started.
RESOLVE is evaluating zelicapavir, Enanta’s investigational RSV nucleoprotein inhibitor, in adult outpatients who test positive for RSV and carry elevated risk of severe outcomes. That population, immunocompromised adults, patients with cardiopulmonary comorbidities, adults over 60, overlaps almost entirely with the patient panels at infectious disease clinics, pulmonology practices, and hospital-affiliated outpatient research centers already fielding competing protocol requests. First patient dosed means site activation is underway globally. The sites that are not ready when the SIV team calls will not be selected, and the sites that are selected but not prepared will spend the first enrollment month burning coordinator hours on protocol queries instead of screening patients.
The Capacity Problem No Feasibility Survey Captures
Here is the operational reality that enrollment forecasts miss: RSV outpatient trials run on a seasonal window. Miss the peak transmission period and your screen rate collapses regardless of site count. A 2024 industry report documented that study conduct timelines grew from 14 months in 2020 to 24 months by 2024, driven in part by site saturation, active research sites facing competing protocol demands with no slack in coordinator capacity. That pressure is sharper in respiratory indications, where a single coordinator handles patient contact, symptom diary reconciliation, and daily safety checks simultaneously during a six-to-eight-week enrollment sprint.
Zelicapavir’s mechanism adds a layer of operational specificity that feasibility teams rarely price in. As an N-protein inhibitor, not a fusion inhibitor, not a polymerase inhibitor, it targets viral replication at a distinct step, which is scientifically meaningful but procedurally demanding: sites must confirm RSV-positive status rapidly enough that treatment initiation falls within the protocol’s enrollment window. For high-risk outpatient antivirals, enrollment windows from symptom onset are typically narrow, often measured in days. A site running RSV diagnostics through a central lab with 48-hour turnaround has already burned half its enrollment eligibility window before the coordinator pulls the eligibility checklist.
That diagnostic lag explains why RESOLVE, and trials like it, require point-of-care RSV testing at the site level as a practical prerequisite, not a preferred option. Sites that submitted feasibility responses citing send-out testing capabilities need to revisit that answer before the SIV. Sponsors will not flag this proactively in every case. Sites should.
The previous Phase 2 data on zelicapavir in high-risk adults offers an additional signal worth reading carefully. Enanta’s earlier study in this population missed its primary endpoint, time to resolution of lower respiratory tract symptoms, while showing directional improvement on secondary measures. That outcome shaped RESOLVE’s design, and sites can expect a primary endpoint structure that demands rigorous, standardized symptom capture. Whatever electronic patient-reported outcome tool the protocol specifies, sites need to complete their ePRO training before the first subject is screened. Symptom resolution endpoints are unforgiving: a missed daily entry is not a minor query, it is a potential protocol deviation with downstream CAPA implications.
Where the Sponsor-Site Handoff Actually Breaks
Trials recruiting high-risk adult outpatients across a mix of decentralized and traditional sites create a coordination friction point that monitoring plans rarely resolve cleanly. Research on fully decentralized respiratory illness trials, including the AcRIS study, shows that remote consent, at-home sample collection, and remote symptom monitoring are technically feasible for acute respiratory infections, but feasibility in a research context is different from operational reliability in a pivotal trial. When a site mixes in-clinic visits with hybrid remote check-ins, the documentation burden increases: you are maintaining source documentation for clinic encounters while also managing remotely collected ePRO data under the same consent framework. Sites running eTMF systems that are not integrated with the trial’s ePRO platform will manage this through manual reconciliation, which means coordinator hours that were not in the original budget negotiation.
The expectation on proportionate monitoring applies here, but proportionate does not mean infrequent when the primary endpoint is patient-reported. Risk-based monitoring plans that rely on central data review for symptom diary completion will surface problems two to three weeks after they occur, which in a six-week RSV outpatient enrollment window means the data integrity problem is already baked in before the CRA opens the flagged listing. Sites I work with in respiratory indications have found that weekly coordinator-to-CRA check-in calls during peak enrollment outperform monthly monitoring visits precisely because the catch window is narrow.
Budget is where sponsor-site friction on these trials becomes concrete. High-risk adult outpatient RSV studies require screen failure coverage that most site contracts underfund. RSV-positive confirmation rates from symptomatic adults presenting in the target risk category vary substantially by season and site, but protocols restrict eligibility by comorbidity profile, prior vaccination status, and symptom onset timing simultaneously. A site may need to screen multiple patients to enroll one. If the per-patient reimbursement structure does not reflect screen failure costs that include coordinator time, POC test kit consumption, and pharmacy review for concomitant medication eligibility, sites will either reduce screening effort or absorb losses that push coordinator overtime into unsustainable territory. Either outcome damages enrollment rate.
What Changes Monday Morning
For site operations teams expecting an SIV call for RESOLVE or any high-risk RSV antiviral trial this season: confirm your POC RSV diagnostic capability and your turnaround time in writing before the SIV, not during it. If your testing flow cannot return a confirmed result within 24 hours of a symptomatic patient contact, that is a site readiness gap that needs a solution before you accept the protocol, not a footnote in the SIV report. Separately, pull your ePRO training completion log now. Symptom-resolution primary endpoints have zero tolerance for incomplete daily entry data, and ICH E6(R3) places source data integrity responsibility squarely on the investigator site.
For sponsor clinical operations teams: the screen failure rate assumption in your enrollment model deserves a direct challenge. If your feasibility team used an optimistic screen-to-enroll ratio for high-risk adult RSV outpatients in a pivotal trial with compound eligibility criteria, that assumption deserves direct challenge. Build the site contract budget around a realistic failure rate now, before sites are activated and under-resourced, because a site that cannot cover its screening costs will slow enrollment in month two, quietly, without escalating, until your CTM notices the screen rate dropped and asks why.
RSV season does not wait for contract amendments. The sites that get this right in the next four weeks will carry RESOLVE’s enrollment curve; the ones that do not will generate the protocol deviation summaries that explain why the interim analysis was delayed.
References
- Clinical Trials Arena, “First patient dosed in Enanta’s Phase IIb/III trial for RSV”
- Enanta Pharmaceuticals, Zelicapavir RSV Pipeline and Mechanism of Action
- MarketScreener, “Enanta Pharmaceuticals Announces First Patient Dosed in the RESOLVE Phase 2b/3 Study of Zelicapavir”
- Contagion Live, “Zelicapavir Shortens RSV Symptoms, Misses Primary Endpoint”
- Fierce Biotech, “Pandemic showed what CROs can do; in 2024 they face heightened expectations” (site saturation and study timeline growth data)
- PMC, Acute Respiratory Illness Surveillance (AcRIS) Study: decentralized trial infrastructure for respiratory infections
- FDA, “Respiratory Syncytial Virus Infection: Developing Antiviral Drugs for Prophylaxis and Treatment, Guidance for Industry”
