Prospective, Randomized, Double Blind, Multicenter Study for an Autocrosslinked Polysaccharide Gel to Evaluate Antiadhesive Effect and Safety Compared to Poloxamer/Sodium Alginate After Thyroidectomy

The aim of the study was to compare the efficacy and safety between an autocrosslinked polysaccharide (ACP) gel (Hyalobarrier) and a poloxamer/sodium alginate (P/SA: Guardix-SG) in preventing adhesions after thyroidectomy and demonstrate the noninferiority of ACP gel to P/SA. To identify differences of antiadhesive efficacy and safety between the ACP gel and P/SA, we investigated various variables such as the proportion of normal esophageal motility as assessed using marshmallow esophagography, swallowing impairment, adhesion severity and so on. This prospective, randomized, double-blinded, multicenter, phase III study investigated the antiadhesive efficacy and safety of ACP gel compared with those of P/SA for 12 weeks. Subjects were randomly assigned to receive either ACP gel (n = 97) or P/SA (n = 96). The primary endpoint was the proportion of normal esophageal motility as assessed using marshmallow esophagography, while the secondary endpoints included swallowing impairment, adhesion severity, laryngoscopic assessment of the vocal cords, and voice range profile. Safety endpoints included adverse events. There was no significant difference between the ACP gel and P/SA groups in the proportion of normal esophageal motility as the primary endpoint (P = 0.7428). In addition, there were no differences in the secondary or safety endpoints between the 2 groups. It was demonstrated that ACP gel was not inferior to P/SA. ACP gel appears both effective and safe for use in preventing adhesions after thyroidectomy.

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Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study

Cephalalgia ◽

10.1177/03331024211024160 ◽

2021 ◽

pp. 033310242110241

Author(s):

Shuu-Jiun Wang ◽

Artemio A Roxas ◽

Bibiana Saravia ◽

Byung-Kun Kim ◽

Debashish Chowdhury ◽

...

Keyword(s):

Latin America ◽

Middle East ◽

Primary Endpoint ◽

Episodic Migraine ◽

Acute Migraine ◽

Efficacy And Safety ◽

Medication Treatment ◽

Significant Difference ◽

Specific Medication ◽

Secondary Endpoints

Objective EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. Methods Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. Results At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was −3.1, −4.2, and −4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. Conclusions This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab’s efficacy and safety to patients under-represented in previous trials. ClinicalTrials.gov identifier: NCT03333109

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Comparing Therapeutic Efficacy and Safety of Epoetin Beta and Epoetin Alfa in the Treatment of Anemia in End-Stage Renal Disease Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000493097 ◽

2018 ◽

Vol 48 (4) ◽

pp. 251-259 ◽

Cited By ~ 2

Author(s):

Jalal Azmandian ◽

Mohammad Reza Abbasi ◽

Vahid Pourfarziani ◽

Amir Ahmad Nasiri ◽

Shahrzad Ossareh ◽

...

Keyword(s):

Body Weight ◽

Hemodialysis Patients ◽

Phase Iii ◽

Efficacy And Safety ◽

Epoetin Alfa ◽

Double Blind ◽

Epoetin Beta ◽

Significant Difference ◽

The Mean ◽

Stage Renal Disease

Background: Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients. Methods: In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10–12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints. Results: A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10–12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group. Conclusion: CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).

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Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV no squamous non-small cell lung cancer (NSCLC) (STELLA study): Results for the primary endpoint in a confirmatory, double-blind, randomized, controlled study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21542 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21542-e21542

Author(s):

Susana Millan ◽

Dmytro Trukhin ◽

Oleksii Kolesnik ◽

Elena Poddubskaya ◽

Andric Zoran ◽

...

Keyword(s):

Primary Endpoint ◽

Objective Response ◽

Stage Iiib ◽

Study Endpoint ◽

Controlled Study ◽

Primary Study ◽

Double Blind ◽

Study Results ◽

Significant Difference ◽

Secondary Endpoints

e21542 Background: MB02 is a proposed biosimilar of the reference bevacizumab. A multinational, double-blind, randomized, parallel group clinical study (STELLA) is undergoing to confirm clinical similarity between MB02 and bevacizumab in patients with stage IIIB/IV no squamous NSCLC. Methods: Subjects were randomized 1:1 to MB02 or bevacizumab (15 mg/kg) plus chemotherapy (paclitaxel [P] 200 mg/m2 and carboplatin [C] AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (Week 52). As primary study endpoint, the efficacy by means of the objective response rate (ORR) evaluated by an independent radiological committee (IRC) was compared between arms at Week 18. Secondary endpoints were Progression Free Survival (PFS) and Overall Survival (OS), safety and immunogenicity (assessed at 18 and 52 weeks). Results: 627 patients were randomized: MB02 (n = 315) and bevacizumab (n = 312). Demographic and baseline characteristics were well balanced between arms. The ORR results were comparable for subjects receiving MB02 or bevacizumab plus P/C. A Risk Ratio (RR) of 1.013 (90% CI: -0.037% to 0.059) and a Risk Difference (RD) of 0.011 (90% CI: -0.037% to 0.059), were within the similarity margin predefined by FDA (0.73, 1.36) and EMA (-12%, +12%) respectively. This ORR assessed by IRC was consistent with the investigator assessment criteria. There was no significant difference between arms for secondary efficacy endpoints (PFS/OS) at week 18. Up to primary endpoint cut-off point, the safety assessment showed no significant differences between MB02 and bevacizumab arms (including the immunogenicity assessment) in terms of nature, frequency and severity of the adverse events (AE), being anaemia and hypertension the most common IMP-related AEs, with a RD between treatment groups < 5%. New signals or observable trends were no reported for MB02-treated subjects. Additional information on the secondary endpoints will be available at week 52 (end of monotherapy period). Conclusions: The statistical analysis executed for ORRs confirm the equivalence of MB02 and bevacizumab, supporting the clinical activity of MB02 treatment. MB02 was well tolerated with manageable AEs in patients with Stage IIIB/IV NSCLC. Clinical trial information: NCT03296163.

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P173 Efficacy and safety of upadacitinib versus placebo and adalimumab in patients with active PsA and inadequate response to non-biologic DMARDs (SELECT-PSA-1): a double-blind, randomised controlled phase III trial

Rheumatology ◽

10.1093/rheumatology/keab247.168 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Iain McInnes ◽

Jaclyn Anderson ◽

Marina Magrey ◽

Joseph F Merola ◽

Yi Liu ◽

...

Keyword(s):

Study Drug ◽

Control Measures ◽

Phase Iii ◽

Musculoskeletal Symptoms ◽

Stock Ownership ◽

Inadequate Response ◽

Efficacy And Safety ◽

Research Support ◽

Double Blind ◽

Secondary Endpoints

Abstract Background/Aims Upadacitinib (UPA) is a JAK inhibitor under evaluation for PsA treatment. We aimed to assess efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients with prior inadequate response (IR) or intolerance to ≥ 1 non-biologic DMARD. This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods Patients with active PsA (≥3 swollen, ≥3 tender joints), active/historical psoriasis, ≤2 non-bDMARDs were randomized 1:1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), ADA 40mg every other week, or PBO. Primary endpoint: proportion of patients achieving ACR20 for UPA vs PBO at Wk12. Secondary endpoints: change in HAQ-DI, FACIT-F, SF-36-PCS (Wk12), sIGA of Psoriasis 0/1, PASI75, change in Self-Assessment of Psoriasis Symptoms (Wk16), change in modified Sharp/van der Heijde Score (mTSS), proportion patients achieving MDA, resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk24), non-inferiority and superiority vs ADA for ACR20, superiority for HAQ-DI, patient assessment of pain NRS (Wk12). Additional secondary endpoints: ACR50/70 at Wk12 and ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) through Wk24 reported for patients receiving ≥1 dose of study drug. Results 1,705 patients were randomised; 1,704 received study drug (mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% on ≥ 1 concomitant non-bDMARD. At Wk12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < 0.001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < 0.001 for UPA15/30 vs ADA; superiority, p < 0.001 for UPA30 vs ADA). More patients achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA30 vs ADA for improvement in pain. At Wk24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). Rates of TEAEs and serious AEs, including serious infections, were similar in PBO, UPA15, and ADA arms and higher with UPA30. Herpes zoster rates were similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in both the PBO and UPA15 arms; 3 malignancies were reported in both UPA30 and ADA arms. VTE were reported in 1 PBO patient, 1 UPA30 patient and 2 ADA patients. One death occurred in the PBO arm. Conclusion In this non-bDMARD-IR PsA population UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue and inhibited radiographic progression; improvements observed by Wk2. At Wk12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO patients achieved stringent disease control measures (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared to the safety profile observed in RA. Disclosure I. McInnes: Other; I.McI has received research grants and honoraria from Abbvie, BMS, Celgene, Novartis Lilly, Janssen, Pfizer, UCB. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. M. Magrey: Consultancies; M.M. has received consulting fees from Novartis, Eli Lilly, Pfizer, and Janssen. Grants/research support; M.M. has received grants/ research support from Amgen, AbbVie, and UCB Pharma. J.F. Merola: Consultancies; J.F.M. is a consultant for Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma. Y. Liu: None. M. Kishimoto: Consultancies; M.K. has received consulting fees from AbbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma. Honoraria; M.K. has received honoraria/ speakers fees from AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma. S. Jeka: None. C. Pacheco-Tena: None. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. L. Chen: Shareholder/stock ownership; L.C. may be a stock/shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. F. Behrens: Honoraria; F.B. has received honoraria and speakers fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grants/ research support from Pfizer, Janssen, Chugai, Celgene and Roche.

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Third-line treatment: A randomized, double-blind, placebo-controlled phase III ALTER-0303 study—Efficacy and safety of anlotinib treatment in patients with refractory advanced NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9053 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9053-9053 ◽

Cited By ~ 5

Author(s):

Baihui Han ◽

Kai Li ◽

Qiming Wang ◽

Yizhuo Zhao ◽

Li Zhang ◽

...

Keyword(s):

Primary Endpoint ◽

Advanced Nsclc ◽

Phase Iii ◽

Line Treatment ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Third Line ◽

Ecog Ps ◽

Third Line Treatment

9053 Background: Anlotinib hydrochloride, an oral TKI targeting VEGFR, FGFR, PDGFR and c-Kit, showed promising efficacy in PhaseⅡstudy. Here, we evaluated the efficacy and safety of anlotinib as third-line treatment for advanced NSCLC, a randomized, double-blind, placebo-controlled Phase Ⅲtrial (ALTER-0303). Methods: Eligible ⅢB/Ⅳ NSCLC pts who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. Enrolled pts harboring EGFR or ALK mutations must had failed in previous match-targeted therapies. The primary endpoint is OS; secondary endpoint includes PFS, DCR and ORR. Results: As of Aug 2016, total of 437 pts from 31 sites were randomized. The baseline characteristics of Anlotinib arm (N=294) and placebo arm (N=143) were well balanced in the age, gender, ECOG PS and gene states. With 292 OS events (66.82%), significant superiorities in OS, PFS, DCR and ORR were observed in Anlotinib arm according to investigator-assessed results. Grade ≥ 3 treatment-related AEs were hypertension, dermal toxicity and hypertriglyceridemia. There was no treatment–related death in either arm. (Data presented in the Table.) Conclusions: ALTER-0303 trial met its primary endpoint. Anlotinib significantly improved OS and PFS in advanced NSCLC with a manageable safety profile. The results strongly suggest that anlotinib should be considered as a candidate for the third-line treatment or beyond in advanced NSCLC. Clinical trial information: NCT02388919. [Table: see text]

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Efficacy and Safety of Different Doses of Bevacizumab Combined With Pemetrexed and Platinum in First-Line Treatment of Advanced NSCLC: A Retrospective-Real World Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.727102 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chun-Hua Zhou ◽

Feng Yang ◽

Wen-Juan Jiang ◽

Yong-Chang Zhang ◽

Hai-Yan Yang ◽

...

Keyword(s):

Primary Endpoint ◽

Statistical Significance ◽

Progression Free Survival ◽

Efficacy And Safety ◽

First Line ◽

Free Survival ◽

Significant Difference ◽

Secondary Endpoints ◽

The Cost ◽

Different Doses

Background: Bevacizumab was demonstrated to have efficacy in patients with NSCLC. However, application of different doses of bevacizumab in different clinical trials was overlooked. This study aims to investigate the effects and safety of different doses of bevacizumab in the treatment.Methods: From January 2016 to March 2020, 79 patients with NSCLC received first-line combination treatment with chemotherapy (pemetrexed + platinum) and bevacizumab for four cycles; patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab combined with pemetrexed, of which 57 patients received bevacizumab at a dose of 7.5 mg/kg and 22 patients at a dose of 15 mg/kg. The primary endpoint was progression-free survival, and secondary endpoints were overall response rate, disease control rate, and adverse events.Results: There was no significant difference between two groups in effectiveness; Median PFS in 7.5 mg/kg group and in 15 mg/kg group were 8.0 and 8.7 months, respectively (p = 0.663), reaching the primary endpoint. The ORR and DCR in the bevacizumab 7.5 and 15 mg/kg group were 45.46 and 86.0% vs. 50 and 90.9% showing no statistical significance (p = 0.804 and 0.717). Most of side effects were tolerable. The incidences of overall toxicities were higher in 15 mg/kg group (p = 0.001). No new safety signals were observed.Conclusion: We did not detect significant difference of efficacy and safety between 7.5 mg/kg group and 15 mg/kg group for bevacizumab administration, the cost-effectiveness of the 7.5 mg/kg group was significantly better than that of the 15 mg/kg group.

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Final results of CONFIRM 2: A multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4033 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4033-4033 ◽

Cited By ~ 16

Author(s):

C. Kohne ◽

E. Bajetta ◽

E. Lin ◽

J. W. Valle ◽

E. Van Cutsem ◽

...

Keyword(s):

Primary Endpoint ◽

Final Analysis ◽

Serum Lactate ◽

Phase Iii ◽

Serum Lactate Dehydrogenase ◽

Double Blind ◽

Strong Activity ◽

Baseline Serum ◽

Secondary Endpoints ◽

Pre Treatment

4033 Background: PTK/ZK, a novel, oral, anti-angiogenic compound that inhibits all VEGF receptors has been investigated in two multinational randomized phase 3 studies in 1st (CONFIRM 1) and 2nd line (CONFIRM 2) mCRC. Interim analyses (IA) have been presented at ASCO 2005 and 2006, respectively. Methods: In CONFIRM 2, 855 pts were randomized to FOLFOX4 plus PTK/ZK (1250 mg, qd), or placebo. Eligibility included histologically documented mCRC, pre-treatment for metastatic disease with irinotecan-/fluoropyrimidine- based therapy, measurable disease by RECIST, PS of 0–2 and adequate organ function. Pts were stratified based on PS (0 vs. 1–2) and baseline serum Lactate Dehydrogenase (LDH = vs. >1.5 × ULN). The primary endpoint is overall survival (OS). Secondary endpoints included OS and PFS in high LDH pts (LDH > 1.5 × ULN). Results: At the time of IA in July 2005, OS was 12.1 mo in the PTK/ZK and 11.8 mo in the placebo arm (HR: 0.94; p=0.511). PFS was significantly longer in the PTK/ZK arm (5.5 mo vs. 4.1 mo; HR: 0.83; p=0.026). LDH, a marker for poor prognosis in mCRC, is predictive of the outcome in the PTK/ZK arm. When treated with PTK/ZK, high LDH pts showed a strong improvement in PFS (5.6 mo vs. 3.8 mo; HR: 0.63; p<0.001) and in OS (9.6 mo vs. 7.5 mo; HR: 0.78; p=0.10). Adverse events (AE) were similar to that of the CONFIRM 1 trial. Final analysis for OS, PFS and safety is planned for Feb. 2007 after 732 events (compared to 413 in the IA) and will be presented at the meeting. Conclusions: While the primary endpoint for OS was not met in the IA, PTK/ZK improves PFS significantly in the overall population, and shows strong activity (improved PFS and OS) in patients with high baseline serum LDH. Final results of the study will be presented at the meeting. No significant financial relationships to disclose.

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Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.510 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 510-510 ◽

Cited By ~ 3

Author(s):

Justin Stebbing ◽

Yauheni Valerievich Baranau ◽

Valery Baryash ◽

Alexey Manikhas ◽

Vladimir Moiseyenko ◽

...

Keyword(s):

Neoadjuvant Treatment ◽

Complete Response ◽

Phase Iii ◽

Efficacy And Safety ◽

Her2 Positive ◽

Double Blind ◽

Secondary Endpoints ◽

Phase Iii Study ◽

To Receive ◽

Related Reaction

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]

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Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-221048 ◽

2021 ◽

pp. annrheumdis-2021-221048

Author(s):

Andrew Östör ◽

Filip Van den Bosch ◽

Kim Papp ◽

Cecilia Asnal ◽

Ricardo Blanco ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Primary Endpoint ◽

Inadequate Response ◽

Efficacy And Safety ◽

Phase 3 ◽

Serious Adverse Events ◽

Double Blind ◽

American College Of Rheumatology ◽

Patient Reported ◽

Secondary Endpoints

ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively.ConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.

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Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3508 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3508-3508 ◽

Cited By ~ 39

Author(s):

C. Koehne ◽

E. Bajetta ◽

E. Lin ◽

E. Van Cutsem ◽

J. Hecht ◽

...

Keyword(s):

Primary Endpoint ◽

Final Analysis ◽

Phase Iii ◽

Double Blind ◽

Strong Activity ◽

Baseline Serum ◽

Poor Prognostic Factor ◽

Secondary Endpoints ◽

Grade 3 ◽

Endothelial Growth Factor

3508 Background: PTK/ZK is a novel, oral, small molecule, antiangiogenic compound that inhibits tyrosine kinase signaling of all known vascular endothelial growth factor (VEGF) receptors. Methods: 855 pts were randomized to FOLFOX4 plus PTK/ZK (1250 mg, qd), or placebo. Eligibility included histologically or cytologically documented mCRC, pretreatment for metastatic disease with irinotecan/fluoropyrimidine-based chemotherapy, measurable disease by RECIST, PS of 0–2 and adequate organ and bone marrow function. The primary endpoint is overall survival (OS). Secondary endpoints included OS and PFS in high LDH pts (stratifiedbybaseline serum LDH levels > 1.5 × ULN). Results: OS was 12.1 mo in the PTK/ZK arm and 11.8 mo in the placebo arm (HR: 0.94; p=0.511). A pre-planned triangular test suggested a low probability of demonstrating an improvement in OS at the final analysis (4Q 2006). The response rates (CR+PR) were 18.5% in the PTK/ZK arm, 17.5% in the placebo arm. PFS was significantly longer in the PTK/ZK arm (5.5 mo vs. 4.1 mo; HR: 0.83; p=0.026). LDH, usually a poor prognostic factor in mCRC, is predictive of the outcome in the PTK/ZK arm. Pts with high LDH showed a strong improvement in PFS when treated with PTK/ZK (5.6 mo vs. 3.8 mo; HR: 0.63; p<0.001) and an improved OS (9.6 mo vs. 7.5 mo; HR: 0.78; p=0.10). Adverse events (AE) were similar to that of the CONFIRM 1 trial (ASCO 2005). Most frequent grade 3/4 AE associated with PTK/ZK were hypertension (PTK/ZK: 21%; placebo: 5%), diarrhea (16%; 8%), fatigue (14.5%; 6.9%), nausea (11%; 5%), vomiting (9%; 5%), dizziness (9%; 1%). AEs were generally reversible. Thrombotic and embolic events of all grades occurred in 6% (PTK/ZK) vs. 1% (placebo) and 4% vs. 1%, respectively. There was no increase in bowel perforations, hematological toxicities or peripheral neuropathy in the PTK/ZK arm. Conclusions: While the primary endpoint for OS was not met, PTK/ZK improves PFS significantly in the overall population, and shows strong activity in patients with high baseline serum LDH. [Table: see text]

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