NCT03350815

Study Estimating the Clinical Difference Between 300 mg and 150 mg of Secukinumab Following Dose Escalation to 300 mg in Patients With Ankylosing Spondylitis

A Randomized, Double-blind, Parallel-group, Multicenter Study of Secukinumab to Compare 300 mg and 150 mg at Week 52 in Patients With Ankylosing Spondylitis Who Are Randomized to Dose Escalation After Not Achieving Inactive Disease During an Initial 16 Weeks of Open-label Treatment With Secukinumab 150 mg (ASLeap)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 322 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a study estimating the clinical difference between 300 mg and 150 mg of secukinumab following dose escalation to 300 mg in patients with ankylosing spondylitis

Detailed description

The study used a multicenter design which included an initial 16 week open-label period (Treatment Period 1) followed by a randomized, double-blind, parallel-group period (Treatment Period 2), 1. Screening: A Screening Period took place over 2 separate visits, with the first visit used to assess eligibility and to washout prohibited medications (up to 11 weeks). The second Screening Visit, which occurred at a minimum of 2 weeks prior to the Baseline Visit for all patients, was used to further assess eligibility and to initiate patients on the sensor actigraphy device and morning sleep questionnaires which collected data over the 2-week Screening Period to establish Baseline data. Note: Patients who did not require a washout, and who satisfied all inclusion and none of the exclusion criteria at the first Screening Visit, could initiate the second Screening Visit 1 (SV1) week after their first Screening Visit. 2. Treatment Period 1: Patients who met all of the inclusion criteria and none of the exclusion criteria had a Baseline Visit performed to start Treatment Period 1. During this 16-week period, all patients received open-label secukinumab 150 mg (1 x 1.0mL subcutaneously \[s.c.\]) at Baseline, Weeks 1, 2, 3, 4, 8, and 12. At Week 16, patients were placed into 1 of the following groups: 1. Responders (Rs): Patients who achieved ASDAS inactive disease (total score \< 1.3) at both Week 12 and Week 16 and who achieved a decrease (improvement) from Baseline in total ASDAS score at both Week 12 and Week 16. 2. Inadequate responders (IRs): Patients who had active disease, defined as an ASDAS total score of ≥ 1.3 at either Week 12 or Week 16, and who achieved a decrease (improvement) from Baseline in total ASDAS score at both Week 12 and Week 16. 3. Nonresponders: Patients who exhibited no change or an increase (worsening) from Baseline in total ASDAS score at either Week 12 or Week 16. Note: To minimize patient burden, at the Week 16 Visit, the hs-CRP measurement that is part of the ASDAS calculation was imputed from the Week 12 hs-CRP results to allow for assignment into the groups above. Historically, hs-CRP levels have varied little between Week 12 and Week 16 or in previous studies of secukinumab in active AS. 1\. Treatment Period 2: Upon completion of the Week 16 visit, 1. Responders entered Treatment Period 2 and continued to receive secukinumab 150 mg every 4 weeks through Week 48 as well as 1 matched placebo dose (s.c. injection) to maintain the integrity of the blind for the randomized IR group. 2. Inadequate responders entered Treatment Period 2 and were randomized (1:1, double blinded) to secukinumab 300 mg or secukinumab 150 mg every 4 weeks through Week 48. Patients knew that they were on secukinumab, but were blinded to dose, so they did not know whether they were receiving 150 mg or 300 mg. 3. Nonresponders were discontinued from the study at Week 16. The only condition that was placed on enrollment targets was that no less than 60% of patients (162 patients) were tumor necrosis factor alpha (TNFα) inhibitor naive (or, no more than 40% of patients were TNF-IR). In theory the percentage of TNFα inhibitor naive patients could have reached 100%, although that was not anticipated. Patients could discontinue the study at any time. If rescue treatment with prohibited medications (as described in Section 9.4.7) occurred, patients were discontinued from the study and were to return for an End of Study Visit. The End of Study Visit was scheduled approximately 4 weeks after the last study treatment and was performed before any new treatment was initiated. After the End of Study Visit, any serious adverse events (SAEs) that occurred in the following 30 days were required to be reported.

Conditions

• Ankylosing Spondylitis

Interventions

Type	Name	Description
DRUG	150 mg open-label secukinumab	All patients in Treatment Period 1 received 150 mg s.c. injection open-label secukinumab.
DRUG	150 mg double-blinded secukinumab	Treatment Period 2 Patients who achieved responder status entered Treatment Period 2 and continued to receive 150 mg s.c. (1 s.c. injection of secukinumab 150 mg)
DRUG	300 mg double-blinded secukinumab	Treatment Period 2 300 mg (2 s.c. injections of the 150 mg dose)

Timeline

• Start date: 2018-03-13
• Primary completion: 2021-03-11
• Completion: 2021-05-29
• First posted: 2017-11-22
• Last updated: 2022-04-29
• Results posted: 2022-04-08

Locations

65 sites across 1 country: United States

Regulatory

• FDA-regulated drug study