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Papers by Arnold Willemsen

Research paper thumbnail of Immunogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with the meningococcal serogroup B (4CMenB) vaccine in infants: A post-hoc analysis in a phase 3b, randomised, controlled trial

Vaccine, 2019

BACKGROUND No data are currently available on immunogenicity of higher-valent pneumococcal conjug... more BACKGROUND No data are currently available on immunogenicity of higher-valent pneumococcal conjugate vaccines when co-administered with a 4-component meningococcal serogroup B vaccine (4CMenB). METHODS Post-hoc analysis of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) immunogenicity when co-administered with 4CMenB (2 + 1 schedule) and/or a CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) in a trial assessing 4CMenB reduced schedules and co-administration with MenC-CRM (NCT01339923). Infants were randomized to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM (Group 2) at 3, 5, and 12 months (M) of age. Both groups received PHiD-CV (3 + 1 schedule) as part of the Brazilian national immunisation programme at 3 M, 5 M, 7 M, and 12 M of age. Antibody responses were assessed pre-vaccination, 1 M post-dose 2, pre-booster, and 1 M post-booster. RESULTS Anti-pneumococcal antibody responses were in similar ranges in the two study groups. CONCLUSIONS 4CMenB co-administration did not seem to impact antibody responses to PHiD-CV in infants.

Research paper thumbnail of Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial

Vaccine, 2018

Background: Invasive meningococcal disease has its highest incidence in infants. Co-administratio... more Background: Invasive meningococcal disease has its highest incidence in infants. Co-administration of serogroup B (4CMenB) and quadrivalent conjugate (MenACWY-CRM) vaccines could protect against 5 clinically-relevant meningococcal serogroups. Methods: This phase 3b, open, multicenter study (NCT02106390), conducted in Mexico and Argentina, enrolled and randomized (1:1:1) 750 healthy infants to receive either 4CMenB co-administered with MenACWY-CRM (4CMenB/MenACWY group), 4CMenB (4CMenB group), or MenACWY-CRM alone (MenACWY group) at ages 3, 5, 7 and 13 months. Non-inferiority of immune responses of coadministration to single administration of vaccines was assessed at 1 month post-booster dose (primary objective). Immunogenicity was evaluated pre-and 1 month post-primary and booster vaccinations using human serum bactericidal assay (hSBA). Safety was assessed. Results: At 1 month post-booster vaccination, between-group hSBA geometric mean titer (GMT) ratios ranged from 0.89 to 1.03 for serogroup B strains (group 4CMenB/MenACWY over 4CMenB), and from 1.05 to 2.48 for ACWY serogroups (group 4CMenB/MenACWY over MenACWY). The lower limit of the 2-sided 95% confidence intervals for all GMT ratios was >0.5; the primary objective was demonstrated. Across all groups and serogroup B strains, 68-100% and 87-100% of children had hSBA titers 5 at 1 month post-primary and booster vaccination, respectively. For serogroups ACWY, 96% (postprimary vaccination) and 98% (post-booster vaccination) of children in all groups had hSBA titers 4. Post-booster vaccination, GMTs increased 5.99-fold from pre-booster values for each strain/serogroup. Solicited adverse events (AEs) were more frequent in groups 4CMenB/MenACWY and 4CMenB than in MenACWY; incidence of all other AEs was similar between groups. Serious AEs were reported for 6, 13, and 11 participants in groups 4CMenB/MenACWY, 4CMenB, and MenACWY, respectively; 1 (group 4CMenB) was considered vaccine-related. Conclusion: Immune responses elicited by co-administration of 4CMenB and MenACWY-CRM was noninferior to single immunization. Co-administration of vaccines was immunogenic and well tolerated in infants. ClinicalTrials.gov: NCT02106390.

Research paper thumbnail of Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: a phase 3, open-label, randomized study

Human vaccines & immunotherapeutics, Jan 16, 2018

Neisseria meningitidis is associated with high mortality and morbidity in infants and children wo... more Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2:1) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to 4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA], porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1 month post-primary and post-booster vaccination, using human serum bactericidal assay (hSBA). Reactogenicity and safety were als...

Research paper thumbnail of A Randomized, Placebo-Controlled Trial of Nandrolone Decanoate in Human Immunodeficiency Virus-Infected Men with Mild to Moderate Weight Loss with Recombinant Human Growth Hormone as Active Reference Treatment

The Journal of Clinical Endocrinology & Metabolism, 2005

Objective: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo ... more Objective: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. Methods: In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. Results: Nandrolone administration was associated with a greater increase in LBM (ϩ1.6 Ϯ 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (ϩ0.4 Ϯ 0.3 kg; P Ͻ 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (ϩ2.5 Ϯ 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (ϩ1.6 Ϯ 0.3 kg), body cell mass (ϩ1.0 Ϯ 0.2 kg), and intracellular water (ϩ0.9 Ϯ 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. Conclusion: We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administrationapproved regimen of rhGH in improving lean body mass in HIVinfected men with mild to moderate weight loss.

Research paper thumbnail of Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial

Research paper thumbnail of Immunogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with the meningococcal serogroup B (4CMenB) vaccine in infants: A post-hoc analysis in a phase 3b, randomised, controlled trial

Vaccine, 2019

BACKGROUND No data are currently available on immunogenicity of higher-valent pneumococcal conjug... more BACKGROUND No data are currently available on immunogenicity of higher-valent pneumococcal conjugate vaccines when co-administered with a 4-component meningococcal serogroup B vaccine (4CMenB). METHODS Post-hoc analysis of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) immunogenicity when co-administered with 4CMenB (2 + 1 schedule) and/or a CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) in a trial assessing 4CMenB reduced schedules and co-administration with MenC-CRM (NCT01339923). Infants were randomized to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM (Group 2) at 3, 5, and 12 months (M) of age. Both groups received PHiD-CV (3 + 1 schedule) as part of the Brazilian national immunisation programme at 3 M, 5 M, 7 M, and 12 M of age. Antibody responses were assessed pre-vaccination, 1 M post-dose 2, pre-booster, and 1 M post-booster. RESULTS Anti-pneumococcal antibody responses were in similar ranges in the two study groups. CONCLUSIONS 4CMenB co-administration did not seem to impact antibody responses to PHiD-CV in infants.

Research paper thumbnail of Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial

Vaccine, 2018

Background: Invasive meningococcal disease has its highest incidence in infants. Co-administratio... more Background: Invasive meningococcal disease has its highest incidence in infants. Co-administration of serogroup B (4CMenB) and quadrivalent conjugate (MenACWY-CRM) vaccines could protect against 5 clinically-relevant meningococcal serogroups. Methods: This phase 3b, open, multicenter study (NCT02106390), conducted in Mexico and Argentina, enrolled and randomized (1:1:1) 750 healthy infants to receive either 4CMenB co-administered with MenACWY-CRM (4CMenB/MenACWY group), 4CMenB (4CMenB group), or MenACWY-CRM alone (MenACWY group) at ages 3, 5, 7 and 13 months. Non-inferiority of immune responses of coadministration to single administration of vaccines was assessed at 1 month post-booster dose (primary objective). Immunogenicity was evaluated pre-and 1 month post-primary and booster vaccinations using human serum bactericidal assay (hSBA). Safety was assessed. Results: At 1 month post-booster vaccination, between-group hSBA geometric mean titer (GMT) ratios ranged from 0.89 to 1.03 for serogroup B strains (group 4CMenB/MenACWY over 4CMenB), and from 1.05 to 2.48 for ACWY serogroups (group 4CMenB/MenACWY over MenACWY). The lower limit of the 2-sided 95% confidence intervals for all GMT ratios was >0.5; the primary objective was demonstrated. Across all groups and serogroup B strains, 68-100% and 87-100% of children had hSBA titers 5 at 1 month post-primary and booster vaccination, respectively. For serogroups ACWY, 96% (postprimary vaccination) and 98% (post-booster vaccination) of children in all groups had hSBA titers 4. Post-booster vaccination, GMTs increased 5.99-fold from pre-booster values for each strain/serogroup. Solicited adverse events (AEs) were more frequent in groups 4CMenB/MenACWY and 4CMenB than in MenACWY; incidence of all other AEs was similar between groups. Serious AEs were reported for 6, 13, and 11 participants in groups 4CMenB/MenACWY, 4CMenB, and MenACWY, respectively; 1 (group 4CMenB) was considered vaccine-related. Conclusion: Immune responses elicited by co-administration of 4CMenB and MenACWY-CRM was noninferior to single immunization. Co-administration of vaccines was immunogenic and well tolerated in infants. ClinicalTrials.gov: NCT02106390.

Research paper thumbnail of Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: a phase 3, open-label, randomized study

Human vaccines & immunotherapeutics, Jan 16, 2018

Neisseria meningitidis is associated with high mortality and morbidity in infants and children wo... more Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2:1) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to 4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA], porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1 month post-primary and post-booster vaccination, using human serum bactericidal assay (hSBA). Reactogenicity and safety were als...

Research paper thumbnail of A Randomized, Placebo-Controlled Trial of Nandrolone Decanoate in Human Immunodeficiency Virus-Infected Men with Mild to Moderate Weight Loss with Recombinant Human Growth Hormone as Active Reference Treatment

The Journal of Clinical Endocrinology & Metabolism, 2005

Objective: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo ... more Objective: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. Methods: In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. Results: Nandrolone administration was associated with a greater increase in LBM (ϩ1.6 Ϯ 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (ϩ0.4 Ϯ 0.3 kg; P Ͻ 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (ϩ2.5 Ϯ 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (ϩ1.6 Ϯ 0.3 kg), body cell mass (ϩ1.0 Ϯ 0.2 kg), and intracellular water (ϩ0.9 Ϯ 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. Conclusion: We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administrationapproved regimen of rhGH in improving lean body mass in HIVinfected men with mild to moderate weight loss.

Research paper thumbnail of Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial