Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2–95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016

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2724. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Healthy Meningococcal Vaccine-Naïve Children (2–9 Years)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2401 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S958-S959

Author(s):

Michael W Simon ◽

Donald Brandon ◽

Shane Christensen ◽

Carmen Baccarini ◽

Emilia Jordanov ◽

...

Keyword(s):

Adverse Events ◽

Injection Site ◽

Conjugate Vaccine ◽

Safety Data ◽

Phase Iii ◽

Meningococcal Vaccine ◽

Serious Adverse Events ◽

Double Blind ◽

Post Vaccination ◽

Quadrivalent Meningococcal Conjugate Vaccine

Abstract Background MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in individuals 6 weeks of age and older. We evaluated the safety and immunogenicity of MenACYW-TT compared with a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-CRM [Menveo®]) in US children 2–9 years of age. Methods In a modified double-blind Phase III study (NCT03077438), 1000 children were randomized to receive one dose of either MenACYW-TT vaccine or MenACWY-CRM vaccine. Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure antibodies against representative meningococcal serogroup strains at baseline and 30 days after vaccination. Safety data were collected up to 6 months post-vaccination. Results Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated for MenACYW-TT compared with MenACWY-CRM at Day 30 compared with baseline. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-CRM administration for all four serogroups (A: 86.4% vs 79.3%; C: 97.8% vs 67.1%; W: 94.8% vs 86.3%; Y: 98.5% vs 90.8%). Similar results were observed in two age substrata (2 to 5 years and 6 to 9 years). Percentages of participants with post-vaccination rSBA titers ≥ 1:128 were comparable between both groups. The safety profiles of MenACYW-TT and MenACWY-CRM were comparable. Reactogenicity at the MenACYW-TT injection site was lower than at the MenACWY-CRM injection site. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study. Conclusion MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with that for the licensed MenACWY-CRM vaccine when administered as a single dose to meningococcal vaccine-naïve children. Disclosures All authors: No reported disclosures.

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Randomized, Controlled Trial of a 13-Valent Pneumococcal Conjugate Vaccine Administered Concomitantly with an Influenza Vaccine in Healthy Adults

Clinical and Vaccine Immunology ◽

10.1128/cvi.00176-12 ◽

2012 ◽

Vol 19 (8) ◽

pp. 1296-1303 ◽

Cited By ~ 39

Author(s):

Robert W. Frenck ◽

Alejandra Gurtman ◽

John Rubino ◽

William Smith ◽

Martin van Cleeff ◽

...

Keyword(s):

Influenza Vaccine ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Controlled Trial ◽

Geometric Mean ◽

Enzyme Linked Immunosorbent Assay ◽

Serious Adverse Events ◽

Double Blind ◽

Group 2 ◽

Group 1

ABSTRACTA randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n= 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessedpost hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ≥4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%;P< 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances.

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Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

Nature Medicine ◽

10.1038/s41591-021-01509-0 ◽

2021 ◽

Author(s):

Kathryn E. Stephenson ◽

Boris Julg ◽

C. Sabrina Tan ◽

Rebecca Zash ◽

Stephen R. Walsh ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Adverse Events ◽

Antiviral Activity ◽

Controlled Trial ◽

Phase 1 ◽

Serious Adverse Events ◽

Double Blind ◽

Cell Counts ◽

Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

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Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211045845 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110458

Author(s):

Mark A. Socinski ◽

Cornelius F. Waller ◽

Tazeen Idris ◽

Igor Bondarenko ◽

Alexander Luft ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

European Medicines Agency ◽

Small Cell Lung ◽

Serious Adverse Events ◽

Double Blind

Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

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Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01014-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 19

Author(s):

S. Dian ◽

V. Yunivita ◽

A. R. Ganiem ◽

T. Pramaesya ◽

L. Chaidir ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Tuberculous Meningitis ◽

Standard Dose ◽

Geometric Mean ◽

Phase Iii ◽

High Dose ◽

Treatment Area ◽

Double Blind ◽

Time Curve

ABSTRACT High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0–24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.)

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A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

Journal of Attention Disorders ◽

10.1177/1087054717751197 ◽

2018 ◽

Vol 24 (2) ◽

pp. 318-325 ◽

Cited By ~ 1

Author(s):

Judy P. M. van Stralen

Keyword(s):

Executive Function ◽

Adverse Events ◽

Extended Release ◽

Rating Scale ◽

Controlled Trial ◽

Severity Of Illness ◽

P Value ◽

Serious Adverse Events ◽

Double Blind ◽

Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

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A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽

10.3390/vaccines8020296 ◽

2020 ◽

Vol 8 (2) ◽

pp. 296

Author(s):

Irina Kiseleva ◽

Irina Isakova-Sivak ◽

Marina Stukova ◽

Marianna Erofeeva ◽

Svetlana Donina ◽

...

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Phase 1 ◽

Healthy Adults ◽

Controlled Study ◽

Temperature Sensitive ◽

Serious Adverse Events ◽

Double Blind ◽

Human Influenza Virus ◽

Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

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Immunogenicity and Safety after Booster Vaccination of Diphtheria, Tetanus, and Acellular Pertussis in Young Adults: an Open Randomized Controlled Trial in Japan

Clinical and Vaccine Immunology ◽

10.1128/cvi.00490-13 ◽

2013 ◽

Vol 20 (12) ◽

pp. 1799-1804 ◽

Cited By ~ 7

Author(s):

Megumi Hara ◽

Kenji Okada ◽

Yuko Yamaguchi ◽

Shingo Uno ◽

Yasuko Otsuka ◽

...

Keyword(s):

Young Adults ◽

Adverse Events ◽

Pertussis Vaccine ◽

Controlled Trial ◽

Geometric Mean ◽

Booster Vaccination ◽

Acellular Pertussis Vaccine ◽

Serious Adverse Events ◽

Booster Immunization ◽

Registration Number

ABSTRACTThe recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.)

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2719. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Adults 18–55 Years of Age

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2396 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S957-S957

Author(s):

James Peterson ◽

James Hedrick ◽

Judy Pan ◽

David Neveu ◽

Emilia Jordanov ◽

...

Keyword(s):

Single Dose ◽

Adverse Events ◽

Conjugate Vaccine ◽

Geometric Mean ◽

Safety Data ◽

The United States ◽

Phase Iii ◽

Meningococcal Vaccine ◽

Post Vaccination ◽

Quadrivalent Meningococcal Conjugate Vaccine

Abstract Background The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the immune lot consistency, and safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals 10–55 years of age. Methods A randomized, modified double-blind, multi-center study (NCT02842853) was conducted in the United States. The study evaluated 3344 meningococcal vaccine naïve adolescents and adults, who were randomly assigned to receive either a single dose of one of the three lots of MenACYW-TT conjugate vaccine or single dose of Menactra® [MenACWY-D]. Serum bactericidal assay with human complement (hSBA) and rabbit complement (rSBA) was used to measure antibodies against serogroups A, C, W, and Y at baseline before vaccination (Day 0) and 30 days post-vaccination. Safety data were collected up to 6 months post-vaccination. Herein we report the performance of MenACYW-TT in adults 18 through 55 years of age (n = 1,807). Results Immune equivalence was demonstrated across all 3 lots of MenACYW-TT conjugate vaccine based on geometric mean titers (GMTs) for all serogroups. Non-inferiority of immune responses, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated between MenACYW-TT and MenACWY-D for all four serogroups at Day 30 compared with baseline. The proportions of individuals (18–55 years) with hSBA ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-D administration for all four serogroups (A: 93.5% vs. 88.1%; C: 93.5% vs. 77.8%; W: 94.5% vs. 80.2%; Y: 98.6% vs. 81.2%). A similar trend was observed for post vaccination GMTs in adult participants. Reactogenicity profiles were comparable across study groups. Most unsolicited adverse events were of grade 1 or grade 2 intensity. No vaccine-related serious adverse events were reported. Conclusion MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with the licensed MenACWY-D vaccine when administered as a single dose to meningococcal vaccine naïve adults. Disclosures All authors: No reported disclosures.

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Inhibition of Interleukin-6 (IL-6) Reverses Anemia In Patients with Advanced Non Small Cell Lung Cancer (NSCLC): Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Blood ◽

10.1182/blood.v116.21.640.640 ◽

2010 ◽

Vol 116 (21) ◽

pp. 640-640 ◽

Cited By ~ 1

Author(s):

Michael W. Schuster ◽

James R Rigas ◽

Sergey V Orlov ◽

Branislav Milovanovic ◽

Kumar Prabhash ◽

...

Keyword(s):

Adverse Events ◽

Clinical Chemistry ◽

Controlled Trial ◽

Safety Data ◽

Primary Objective ◽

Serious Adverse Events ◽

Double Blind ◽

Reactive Protein ◽

Grade 3 ◽

Cancer Related Anemia

Abstract Abstract 640 Background: ALD518 is a humanized, desialyated anti-IL-6 antibody being developed for the treatment of cancer-related anemia, cachexia and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518 in patients with advanced NSCLC. Secondary objectives examined hematologic parameters. Methods: 124 patients with NSCLC, ECOG 0–3, weight loss in the preceding 3 months of >5% body weight, hemoglobin (Hb) >7g/dL, and C-reactive protein (CRP) >10mg/L were dosed. Patients were randomized to 1 of 4 groups (n~30/group). Placebo or ALD518 80mg, 160mg, or 320mg was administered intravenously every 8 weeks. Pts were followed up for 24 weeks. Data included hematologic parameters, clinical chemistry, CRP, D-dimer, lean body mass and adverse events (AEs). Quality of life data included the FACIT-F, FACT-L, and FAACT questionnaires. Data presented in this abstract relates to the safety and hematology results. Results: 29 pts completed the study treatments and evaluations, 38 failed to complete every visit, 52 died of progressive disease, and 5 withdrew because of adverse events. There were no dose limiting toxicities (DLTs), infusion reactions, or anti-idiotypic antibody responses to ALD518 observed in the study. 84 pts had serious AEs of which 1 was deemed to be possibly related to administration of ALD518 (rectal hemorrhage). The majority of the serious adverse events were due to progression of the NSCLC. Six patients had a CTC grade 4 change in laboratory safety data during the study. Four patients experienced a grade 4 hypercalcemia: 1 (3.6%), 2 (6.1%), and 1 (3.2%) in the ALD518 80mg, 160mg and placebo groups, respectively, and there was 1 patient with grade 4 GGT elevation (placebo) and 1 patient with grade 4 hypokalemia (ALD518 160mg). There were no treatment related differences in vitals sign or 12-lead ECG data. The mean (±SD) values for Hb, hematocrit (Hct), mean corpuscular Hb (MCH) and platelet counts are listed below: 38/93 pts treated with ALD518 and 10/31 given placebo had a pre-dose Hb =< 11g/dL. 24 of these pts on ALD518 and 7 of these pts on placebo remained in the study at week 4. 14/24 pts on ALD518 and 0/7 on placebo had raised their Hb from =< 11g/dL to >= 12g/dL. Conclusions: ALD518 increased Hb, Hct, MCH in NSCLC pts and raised Hb to >= 12g/dL in 58% of pts with a Hb =< 11g/dL at baseline. There was also a modest fall in platelet count observed in patients treated with ALD518 but no patients had a CTC grade 4 thrombocytopenia and only one patient (ALD518 160mg group) had a grade 3 thrombocytopenia at one time point. There were no major safety signals related to the administration of ALD518. Further study of ALD518 as a novel non-erythropoietic stimulating agent for cancer-related anemia is warranted. Disclosures: Schuster: Alder Biopharmaceuticals Inc: Honoraria. Rigas: Alder Biopharmaceuticals inc: Honoraria. Smith:Alder Biopharmaceuticals Inc: Employment.

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