Long‑Term Safety and Efficacy of SPY001‑001 Monotherapy and Combination Therapy with Long‑Acting Antibodies in Adults with Ulcerative Colitis

The primary objective is to evaluate the ulcerative colitis safety and tolerability profile of long‑acting antibody regimens administered as monotherapy or in combination, thereby determining the acceptability of chronic exposure for therapeutic use. Secondary objectives include assessment of clinical efficacy at Week 48, providing data on disease activity improvement and informing long‑term therapeutic benefit. Additional outcomes address pharmacokinetic characterization, therapeutic response, and overall treatment effect, supporting a comprehensive appraisal of both safety and efficacy parameters.

The trial enrolled 417 individuals diagnosed with ulcerative colitis. Both female and male participants were eligible, and the age distribution corresponded to the categories identified by codes 3 and 4. All subjects were patients who had previously participated in Study SPY123-201 and met one of the following conditions: completion of Part A with investigator‑determined clinical benefit, completion of Part B, or participation in Part B with escape criteria after insufficient improvement or disease worsening during induction or maintenance phases. Selection required prior exposure to the study drug regimens and assessment of disease activity, ensuring a population with established disease status appropriate for evaluating safety and tolerability. General health status was limited to individuals with active ulcerative colitis meeting the specified protocol criteria, without additional lifestyle restrictions reported.

The study is a multicenter, randomized, double‑blind, placebo‑controlled phase 4 trial evaluating the long‑term safety and efficacy of subcutaneously administered long‑acting antibodies (SPY001‑001, SPY002, SPY003) alone or in combination versus placebo in participants with Ulcerative colitis. Eligible individuals are enrolled after a screening visit confirming prior participation in protocol SPY123‑201 and receipt of clinical benefit, completion of Part B, or meeting predefined escape criteria. Following randomization, participants receive study medication at prescribed intervals and attend scheduled visits at baseline, weeks 4, 12, 24, 36, and 48, with the final end‑of‑study visit at week 48 to assess the primary safety endpoint (incidence of treatment‑emergent adverse events) and secondary endpoint (endoscopic improvement). The overall participant involvement spans approximately 48 weeks of treatment and follow‑up. Early termination may occur for any of the following reasons: occurrence of a serious adverse event related to study drug, failure to adhere to the dosing schedule, withdrawal of consent, or the investigator’s determination that continued participation is not in the participant’s best interest. Recruitment is planned to commence in July 2026 with an anticipated study completion in July 2031.

The investigational product SPY001-001 is supplied as a sterile solution for injection intended for subcutaneous administration. Each dose consists of a solution with a concentration of 0 mg/ml, and the volume administered is defined in the protocol. Dosing is performed at the prescribed intervals, which may include a single administration or repeated injections according to the study schedule. Administration is conducted by qualified personnel, and adherence to the dosing regimen is documented through site‑recorded logs and participant diaries.

The investigational product SPY002 is provided as a sterile solution for injection for subcutaneous delivery. The preparation contains 0 mg/ml of active substance, with the administered volume specified by the study protocol. Dosing follows the same schedule as other test agents, with injections given at predetermined time points. Compliance is monitored by recording each administration in the electronic case report form and by reviewing participant self‑reporting tools.

The investigational product SPY003 is a sterile solution for injection intended for subcutaneous use. Each dose contains 0 mg/ml of the active ingredient, and the exact volume is outlined in the dosing schedule. Injections are administered according to the protocol‑defined timeline, and participant compliance is tracked through site documentation and periodic compliance checks.

The control arm utilizes placebo SPYPBO-101, which contains no active pharmaceutical ingredient and is presented as a non‑active solution for injection. It is administered by the same subcutaneous route and schedule as the active products to maintain blinding. Administration details, including timing and volume, are recorded in the same manner as for the investigational agents, ensuring consistent monitoring of adherence across all study arms.

Efficacy will be evaluated by assessing endoscopic improvement at Week 48. Endoscopic examinations are planned at baseline and at the Week 48 visit, with mucosal healing quantified using the study‑specified endoscopic scoring system. The proportion of participants meeting predefined improvement criteria will be calculated and compared across treatment groups.