scholarly journals 626. The Efficacy and Safety of Maintenance with Doravirine Plus Two NRTIs after Initial Suppression in Adults with HIV-1 in the DRIVE-FORWARD Clinical Trial: Results from the Study Extension through 192 Weeks

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S417-S417
Author(s):  
Pedro Cahn ◽  
Jean-michel Molina ◽  
Johan Lombaard ◽  
Kathleen Squires ◽  
Sushma Kumar ◽  
...  
Keyword(s):  
Weight Gain ◽  
Panel Member ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Open Label ◽  
Review Panel ◽  
Double Blind ◽  
Open Label Extension ◽  
Favorable Safety ◽  
Hiv 1

Abstract Background DRIVE-FORWARD is a phase 3 trial with a completed double-blind period comparing doravirine (DOR) 100 mg with ritonavir-boosted darunavir (DRV/r) 800/100 mg, both administered with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs; tenofovir and emtricitabine, or abacavir and lamivudine), and an ongoing open-label extension. At Week (W) 48, DOR demonstrated non-inferior efficacy to DRV/r, with a superior lipid profile. Those results were sustained at W96. Here we present efficacy and safety results through W192. Methods Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR plus two NRTIs in a 96-week extension. Efficacy and safety at W192 were assessed in two groups: participants initially randomized to DOR and maintained on DOR (n=259) and those who switched from DRV/r to DOR at W96 (n=233). Results HIV-1 RNA < 50 copies/mL were maintained through W192 in 81.1% of participants who continued DOR and 80.7% of those who switched from DRV/r to DOR. The mean increase in CD4 T-cell counts from W96 to W192 was similar for participants maintained on DOR (47 cells/mm3) and those switched from DRV/r (53 cells/mm3). Protocol-defined virologic failure occurred in 3.1% and 5.6% of participants maintained on DOR and switched from DRV/r, respectively, and development of genotypic resistance was low in both groups (Table 1). Discontinuation due to adverse events was also low (Table 1). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal increase in participants maintained on DOR and were reduced in those switched from DRV/r to DOR (Table 1). Participants maintained on DOR had minimal weight gain after W96 (median 1 kg), and a small increase overall (median 1.9 kg, Day 1 through W192); participants who switched to DOR had a small increase after W96 (median 1.5 kg), similar to the median weight gain in the base study (DOR 1.8 kg; DRV/r 0.7 kg). Conclusion Among participants who continued DOR in the DRIVE-FORWARD open-label extension, virologic suppression and favorable safety were maintained for an additional 96 weeks. Participants who switched from DRV/r to DOR maintained virologic suppression and demonstrated favorable safety for 96 weeks. Disclosures Pedro Cahn, MD, PHD, Merck (Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Kathleen Squires, MD, Merck (Employee) Sushma Kumar, PhD, Merck (Employee) Hong Wan, PhD, Merck (Employee) Valerie Teal, MS, Merck (Employee) Ernest Asante-Appiah, PhD, Merck (Employee) Peter Sklar, MD, Merck (Employee) Elizabeth A. Martin, DO, MPH, MBA, Merck (Employee) Rima Lahoulou, n/a, Merck (Employee)

scholarly journals Two-year efficacy and safety of erenumab in participants with episodic migraine and 2–4 prior preventive treatment failures: results from the LIBERTY study

2021 ◽  
pp. jnnp-2021-327480
Author(s):  
Michel Dominique Ferrari ◽  
Uwe Reuter ◽  
Peter J Goadsby ◽  
Gabriel Paiva da Silva Lima ◽  
Subhayan Mondal ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Registration Number

ObjectiveTo evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed.MethodsParticipants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability.ResultsOverall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was −4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain.ConclusionsEfficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2–4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies.Trial registration numberNCT03096834

Etanercept in the Longterm Treatment of Patients With Ankylosing Spondylitis

2009 ◽  
Vol 36 (6) ◽  
pp. 1256-1264 ◽  
Author(s):  
BEN DIJKMANS ◽  
PAUL EMERY ◽  
MARKKU HAKALA ◽  
MARJATTA LEIRISALO-REPO ◽  
EMILIO MARTIN MOLA ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Safety Data ◽  
Blind Study ◽  
Double Blind Study ◽  
Upper Respiratory Tract ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Tract Infections

Objective.To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).Methods.A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline.Results.The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n = 30; 37.0%) and headache (n = 18; 22.2%), and the most frequent infections were upper respiratory tract infections (n = 43; 53.1%) and flu syndrome (n = 22; 27.2%).Conclusion.For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.

scholarly journals 1768. Efficacy and Safety of Switching From Boosted-Protease Inhibitors (bPI) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Regimens to the Once Daily (QD), Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-Infected Adults: Week 96 Results of the Phase 3, Randomized, Non-Inferiority EMERALD Trial

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S65-S65 ◽  
Author(s):  
Joseph Eron ◽  
Chloe Orkin ◽  
Douglas Cunningham ◽  
Federcio Pulido ◽  
Frank Post ◽  
...  
Keyword(s):  
Extension Phase ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Genetic Barrier ◽  
Independent Contractor ◽  
Grant Recipient ◽  
Hiv 1 ◽  
Research Grant

Abstract Background The QD STR D/C/F/TAF 800/150/200/10 mg was noninferior to bPI + F/TDF at 48 weeks in EMERALD. Efficacy and safety of D/C/F/TAF through week 96 are presented. Methods EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter noninferiority trial. Virologically suppressed (VL<50 c/mL for ≥2 months) ART experienced (previous non-DRV VF allowed) HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue bPI + F/TDF over 48 weeks. Patients could then continue on D/C/F/TAF or switch from bPI + F/TDF to D/C/F/TAF at week 52 (Late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase until week 96. The percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96 were primary and secondary endpoints, respectively. Results Of 1141 randomized and treated patients (58% had received ≥5 previous ARVs including screening ARVs; 15% had previous non-DRV VF), 1,080 continued in the extension phase (N = 728 D/C/F/TAF; N = 352 late switch). Few patients had virologic rebound cumulative through week 96 in the D/C/F/TAF arm (3.1%, 24/763). Virologic rebound occurred in 2.3% (8/352) in the late switch arm over 44 weeks D/C/F/TAF treatment. Many rebounders (14/24 and 2/8) resuppressed by week 96. At week 96 a high percentage of patients in the D/C/F/TAF arm (90.7%, 692/763) were suppressed (VL<50 c/mL). In the late switch arm, 93.8% (330/352) maintained virologic suppression after 44 weeks of treatment. No DRV, primary PI, TFV, or FTC RAMs were seen post baseline. Few serious AEs and AE related discontinuations occurred in either arm (Table 1). Improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and seen in the late switch arm (week 52–96), with a small change in TC/HDL-C ratio (Table 1). Conclusion Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles. Efficacy and safety results in the late switch arm were consistent with week 48 results in the D/C/F/TAF arm. D/C/F/TAF combines the efficacy and high genetic barrier to resistance of DRV with the safety benefits of TAF, even in patients with a history of non-DRV VF. Disclosures J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant. F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support and Speaker honorarium. F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee. S. De Wit, Janssen: Investigator, Research grant. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee. E. Van Landuyt, Janssen: Employee and Shareholder, Salary.

scholarly journals Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

2017 ◽  
Vol 76 (12) ◽  
pp. 1986-1991 ◽  
Author(s):  
Paul Emery ◽  
Jiří Vencovský ◽  
Anna Sylwestrzak ◽  
Piotr Leszczyński ◽  
Wieslawa Porawska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Open Label Extension ◽  
Extension Period

ObjectivesSB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4.MethodsIn the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100.ResultsOf 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer.ConclusionsSB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.Trial registration numberNCT01895309; 2012-005026-30

scholarly journals Phase 3 Safety and Tolerability Results of the Combination Olanzapine and Samidorphan in Patients with Schizophrenia: The 1 Year ENLIGHTEN-2-Extension

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 155-156
Author(s):  
Rene Kahn ◽  
Bernard Silverman ◽  
Lauren DiPetrillo ◽  
Christine Graham ◽  
Ying Jiang ◽  
...  
Keyword(s):  
Weight Gain ◽  
Waist Circumference ◽  
Extension Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Laboratory Parameters ◽  
Syndrome Scale ◽  
Open Label Extension ◽  
Negative Syndrome

AbstractObjectiveCombination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.Results265 patients received OLZ/SAM; 167 (63.0%) completed the extension study. Common AEs (= 5%) were weight decreased (n=23; 8.7%), extra dose administered (n=21; 7.9%), headache (n=18; 6.8%), and weight increased (n=16; 6.0%). At week 52, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.ConclusionsOLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.FundingAlkermes, Inc.

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