Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results

Gavin Giovannoni, O. Barbarash, F. Casset-Semanaz, J. King, L. Metz, G. Pardo, J. Simsarian, P. S. Sørensen, B. Stubinski, A. Carra, E. Cristiano, G. Luetic, A. Rodriguez Alfici, Godoy Cruz, S. Vetere, J. Pollard, K. Boundy, L. Sedal, H. Butzkueven, R. MacDonnellL. M. Metz, R. K. Zabad, P. Soelberg Sørensen, O. Hardiman, N. Tubridy, D. Karussis, A. Achiron, A. Vaitkus, R. Kizlaitiene, O. Lesnyak, L. Zaslavsky, I. Poverennova, P. Sidorov, D. Khasanova, V. Alifirova, B. Casanova, V. Balyazin, M. Lutsky, A. Rodríguez-Antigüedad, J. García-Merino, R. Arroyo, T. Olsson, D. Barnes, C. Young, J. O'Riordan, O. Malik, R. Armstrong, C. Sheppard, B. Thrower, S. Wray, J. Gross, D. Wynn, T. Miller, G. Garmany, M. Sherman

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background: A new formulation of subcutaneous (s.c.) interferon-β-1a has been developed (Rebif® New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. Objectives: This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. Methods: Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 μg s.c. three times weekly. Results: The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status ≥ 20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4% (exact 95% confidence interval [CI]: 13.0 - 22.5), compared with 21.4% (95% CI: 17.2 - 26.2) in the EVIDENCE study, and 27.3% (95% CI: 22.8 - 32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9% (95% CI: 14.4 - 24.2), compared with 27.1% (95% CI: 22.4 - 32.2) and 33.7% (95% CI: 28.9 - 38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. Conclusions: RNF has improved overall immunogenicity and safety profiles compared with the original formulation.

Original languageEnglish (US)
Pages (from-to)219-228
Number of pages10
JournalMultiple Sclerosis
Volume15
Issue number2
DOIs
StatePublished - Feb 9 2009
Externally publishedYes

Fingerprint

Interferons
Multiple Sclerosis
Confidence Intervals
Safety
Injections
Excipients
Neutralizing Antibodies
Serum
Serum Albumin
Interferon beta-1a
Observation

Keywords

  • Immunogenicity
  • Injection-site reactions
  • Interferon-β-1a
  • Multiple sclerosis
  • Rebif® New Formulation
  • Safety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis : 96-week results. / Giovannoni, Gavin; Barbarash, O.; Casset-Semanaz, F.; King, J.; Metz, L.; Pardo, G.; Simsarian, J.; Sørensen, P. S.; Stubinski, B.; Carra, A.; Cristiano, E.; Luetic, G.; Rodriguez Alfici, A.; Cruz, Godoy; Vetere, S.; Pollard, J.; Boundy, K.; Sedal, L.; Butzkueven, H.; MacDonnell, R.; Metz, L. M.; Zabad, R. K.; Soelberg Sørensen, P.; Hardiman, O.; Tubridy, N.; Karussis, D.; Achiron, A.; Vaitkus, A.; Kizlaitiene, R.; Lesnyak, O.; Zaslavsky, L.; Poverennova, I.; Sidorov, P.; Khasanova, D.; Alifirova, V.; Casanova, B.; Balyazin, V.; Lutsky, M.; Rodríguez-Antigüedad, A.; García-Merino, J.; Arroyo, R.; Olsson, T.; Barnes, D.; Young, C.; O'Riordan, J.; Malik, O.; Armstrong, R.; Sheppard, C.; Thrower, B.; Wray, S.; Gross, J.; Wynn, D.; Miller, T.; Garmany, G.; Sherman, M.

In: Multiple Sclerosis, Vol. 15, No. 2, 09.02.2009, p. 219-228.

Research output: Contribution to journalArticle

Giovannoni, G, Barbarash, O, Casset-Semanaz, F, King, J, Metz, L, Pardo, G, Simsarian, J, Sørensen, PS, Stubinski, B, Carra, A, Cristiano, E, Luetic, G, Rodriguez Alfici, A, Cruz, G, Vetere, S, Pollard, J, Boundy, K, Sedal, L, Butzkueven, H, MacDonnell, R, Metz, LM, Zabad, RK, Soelberg Sørensen, P, Hardiman, O, Tubridy, N, Karussis, D, Achiron, A, Vaitkus, A, Kizlaitiene, R, Lesnyak, O, Zaslavsky, L, Poverennova, I, Sidorov, P, Khasanova, D, Alifirova, V, Casanova, B, Balyazin, V, Lutsky, M, Rodríguez-Antigüedad, A, García-Merino, J, Arroyo, R, Olsson, T, Barnes, D, Young, C, O'Riordan, J, Malik, O, Armstrong, R, Sheppard, C, Thrower, B, Wray, S, Gross, J, Wynn, D, Miller, T, Garmany, G & Sherman, M 2009, 'Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results', Multiple Sclerosis, vol. 15, no. 2, pp. 219-228. https://doi.org/10.1177/1352458508097299
Giovannoni, Gavin ; Barbarash, O. ; Casset-Semanaz, F. ; King, J. ; Metz, L. ; Pardo, G. ; Simsarian, J. ; Sørensen, P. S. ; Stubinski, B. ; Carra, A. ; Cristiano, E. ; Luetic, G. ; Rodriguez Alfici, A. ; Cruz, Godoy ; Vetere, S. ; Pollard, J. ; Boundy, K. ; Sedal, L. ; Butzkueven, H. ; MacDonnell, R. ; Metz, L. M. ; Zabad, R. K. ; Soelberg Sørensen, P. ; Hardiman, O. ; Tubridy, N. ; Karussis, D. ; Achiron, A. ; Vaitkus, A. ; Kizlaitiene, R. ; Lesnyak, O. ; Zaslavsky, L. ; Poverennova, I. ; Sidorov, P. ; Khasanova, D. ; Alifirova, V. ; Casanova, B. ; Balyazin, V. ; Lutsky, M. ; Rodríguez-Antigüedad, A. ; García-Merino, J. ; Arroyo, R. ; Olsson, T. ; Barnes, D. ; Young, C. ; O'Riordan, J. ; Malik, O. ; Armstrong, R. ; Sheppard, C. ; Thrower, B. ; Wray, S. ; Gross, J. ; Wynn, D. ; Miller, T. ; Garmany, G. ; Sherman, M. / Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis : 96-week results. In: Multiple Sclerosis. 2009 ; Vol. 15, No. 2. pp. 219-228.
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title = "Safety and immunogenicity of a new formulation of interferon β-1a (Rebif{\circledR} New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results",
abstract = "Background: A new formulation of subcutaneous (s.c.) interferon-β-1a has been developed (Rebif{\circledR} New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. Objectives: This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. Methods: Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 μg s.c. three times weekly. Results: The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status ≥ 20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4{\%} (exact 95{\%} confidence interval [CI]: 13.0 - 22.5), compared with 21.4{\%} (95{\%} CI: 17.2 - 26.2) in the EVIDENCE study, and 27.3{\%} (95{\%} CI: 22.8 - 32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9{\%} (95{\%} CI: 14.4 - 24.2), compared with 27.1{\%} (95{\%} CI: 22.4 - 32.2) and 33.7{\%} (95{\%} CI: 28.9 - 38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. Conclusions: RNF has improved overall immunogenicity and safety profiles compared with the original formulation.",
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author = "Gavin Giovannoni and O. Barbarash and F. Casset-Semanaz and J. King and L. Metz and G. Pardo and J. Simsarian and S{\o}rensen, {P. S.} and B. Stubinski and A. Carra and E. Cristiano and G. Luetic and {Rodriguez Alfici}, A. and Godoy Cruz and S. Vetere and J. Pollard and K. Boundy and L. Sedal and H. Butzkueven and R. MacDonnell and Metz, {L. M.} and Zabad, {R. K.} and {Soelberg S{\o}rensen}, P. and O. Hardiman and N. Tubridy and D. Karussis and A. Achiron and A. Vaitkus and R. Kizlaitiene and O. Lesnyak and L. Zaslavsky and I. Poverennova and P. Sidorov and D. Khasanova and V. Alifirova and B. Casanova and V. Balyazin and M. Lutsky and A. Rodr{\'i}guez-Antig{\"u}edad and J. Garc{\'i}a-Merino and R. Arroyo and T. Olsson and D. Barnes and C. Young and J. O'Riordan and O. Malik and R. Armstrong and C. Sheppard and B. Thrower and S. Wray and J. Gross and D. Wynn and T. Miller and G. Garmany and M. Sherman",
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day = "9",
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volume = "15",
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TY - JOUR

T1 - Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis

T2 - 96-week results

AU - Giovannoni, Gavin

AU - Barbarash, O.

AU - Casset-Semanaz, F.

AU - King, J.

AU - Metz, L.

AU - Pardo, G.

AU - Simsarian, J.

AU - Sørensen, P. S.

AU - Stubinski, B.

AU - Carra, A.

AU - Cristiano, E.

AU - Luetic, G.

AU - Rodriguez Alfici, A.

AU - Cruz, Godoy

AU - Vetere, S.

AU - Pollard, J.

AU - Boundy, K.

AU - Sedal, L.

AU - Butzkueven, H.

AU - MacDonnell, R.

AU - Metz, L. M.

AU - Zabad, R. K.

AU - Soelberg Sørensen, P.

AU - Hardiman, O.

AU - Tubridy, N.

AU - Karussis, D.

AU - Achiron, A.

AU - Vaitkus, A.

AU - Kizlaitiene, R.

AU - Lesnyak, O.

AU - Zaslavsky, L.

AU - Poverennova, I.

AU - Sidorov, P.

AU - Khasanova, D.

AU - Alifirova, V.

AU - Casanova, B.

AU - Balyazin, V.

AU - Lutsky, M.

AU - Rodríguez-Antigüedad, A.

AU - García-Merino, J.

AU - Arroyo, R.

AU - Olsson, T.

AU - Barnes, D.

AU - Young, C.

AU - O'Riordan, J.

AU - Malik, O.

AU - Armstrong, R.

AU - Sheppard, C.

AU - Thrower, B.

AU - Wray, S.

AU - Gross, J.

AU - Wynn, D.

AU - Miller, T.

AU - Garmany, G.

AU - Sherman, M.

PY - 2009/2/9

Y1 - 2009/2/9

N2 - Background: A new formulation of subcutaneous (s.c.) interferon-β-1a has been developed (Rebif® New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. Objectives: This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. Methods: Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 μg s.c. three times weekly. Results: The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status ≥ 20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4% (exact 95% confidence interval [CI]: 13.0 - 22.5), compared with 21.4% (95% CI: 17.2 - 26.2) in the EVIDENCE study, and 27.3% (95% CI: 22.8 - 32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9% (95% CI: 14.4 - 24.2), compared with 27.1% (95% CI: 22.4 - 32.2) and 33.7% (95% CI: 28.9 - 38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. Conclusions: RNF has improved overall immunogenicity and safety profiles compared with the original formulation.

AB - Background: A new formulation of subcutaneous (s.c.) interferon-β-1a has been developed (Rebif® New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. Objectives: This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. Methods: Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 μg s.c. three times weekly. Results: The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status ≥ 20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4% (exact 95% confidence interval [CI]: 13.0 - 22.5), compared with 21.4% (95% CI: 17.2 - 26.2) in the EVIDENCE study, and 27.3% (95% CI: 22.8 - 32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9% (95% CI: 14.4 - 24.2), compared with 27.1% (95% CI: 22.4 - 32.2) and 33.7% (95% CI: 28.9 - 38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. Conclusions: RNF has improved overall immunogenicity and safety profiles compared with the original formulation.

KW - Immunogenicity

KW - Injection-site reactions

KW - Interferon-β-1a

KW - Multiple sclerosis

KW - Rebif® New Formulation

KW - Safety

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