A two-arm, randomised, double-blind, placebo-controlled, multicenter phase II study to evaluate safety and tolerability and to explore the neuroprotective effect of atacicept as assessed by Optical Coherence Tomography (OCT) in subjects with Optic Neuritis (ON) as Clinically Isolated Syndrome (CIS) over a 36 week treatment course - Atacicept in Optic Neuritis, Phase II

• Conditions: Optic Neuritis; MedDRA version: 13.1Level: PTClassification code 10030942Term: Optic neuritisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2007-003925-26-GB
• Lead Sponsor: Merck Serono S.A. - Geneva

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-13
• Last Update Posted: 11 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

1. Diagnosis of unilateral symptomatic optic neuritis as first clinical manifestation within 28 days of SD1;
2. Male or female between 18-60 years old, inclusive, at the time that informed consent is obtained;
3. Written informed consent, given before any study-related procedure. Subjects must have read and understood the Informed Consent Form, must fully understand the requirements of the study and must be willing to comply with all study visits and assessments.
4. Women of childbearing potential must not be breast feeding and have a negative serum pregnancy test at initial screening and a urine pregnancy test at Study Day 1 before dosing. For the purpose of this study, women of childbearing potential are defined as all female patients after puberty unless they are post-menopausal for at least 2 years or surgically sterile.
5.Female subjects of childbearing potential must be willing to avoid pregnancy by using adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 12 weeks after the last dose of study medication. This requirement does not apply to surgically sterile subjects or to subjects who are post-menopausal for at least 2 years. Adequate contraception is defined as follows: two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of a combined female hormonal contraceptive.
6. Be willing and able to comply with study procedures for the duration of the study;
7. Voluntarily provide written informed consent (obtained before any trial related procedure), including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to their future medical care.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
;
1. Diagnosis of unilateral symptomatic optic neuritis as first clinical manifestation within 28 days of SD1;
2. Male or female between 18-60 years old, inclusive, at the time that informed consent is obtained;
3. Written informed consent, given before any study-related procedure. Subjects must have read and understood the Informed Consent Form, must fully understand the requirements of the study and must be willing to comply with all study visits and assessments.
4. Women of childbearing potential must not be breast feeding and have a negative serum pregnancy test at initial screening and a urine pregnancy test at Study Day 1 before dosing. For the purpose of this study, women of childbearing potential are defined as all female patients after puberty unless they are post-menopausal for at least 2 years or surgically sterile.
5.Female subjects of childbearing potential must be willing to avoid pregnancy by using adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 12 weeks after the last dose of study medication. This requirement does not apply to surgically sterile subjects or to subjects who are post-menopausal for at least 2 years. Adequate contraception is defined as follows: two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of a combined female hormonal contraceptive.
6. Be willing and able to comply with study procedures for the duration of the study;
7. Voluntarily provide written informed consent (obtained before any trial related procedure), including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to their future medical care.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History of ON prior to current ON attack;
2. Bilateral optic neuritis;
3. Diagnosis of MS;
4. Diagnosis of Devic’s disease;
5. Co-morbid ocular condition not related to optic neuritis (ascertained by detailed history and examination, including glaucoma, hypoplasia of the optic nerve, macular hole, vitreomacular traction, diabetes, or other diseases of the optic nerve);
6. Non-evaluable OCT at screening visit due to edema in the affected eye defined as follows:RNFL thickness more than 10 micrometer above normal in 2 or more sectors, or RNFL thickness greater than 200 micrometer in any of the 12 sectors;
7. Severe myopia superior to 5 diopters;
8. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments (such as, but not limited to, significant nervous system, renal, hepatic, endocrine or gastrointestinal disorders), which in the Investigator’s opinion constitutes a risk or a contraindication for the subject’s participation in the study or that could interfere with the study objectives, conduct or evaluation.
9. Prior treatment with B cell modulating therapies, such as rituximab or belimumab;
10. Prior exposure to immunomodulatory therapy, such as interferon beta or glatiramer acetate;
11. Prior exposure to immunosuppressive or cytotoxic agents including but not restricted to cladribine, mitoxantrone, alemtuzumab, cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, or natalizumab;
12. Prior myelosuppressive / cytotoxic therapy, such as lymphoid irradiation, or bone marrow transplantation;
13. Prior use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIg) or plasmapheresis;
14. Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 60 days prior to SD1 except the optional corticosteroid course to treat the initial ON event;
15. Require chronic or monthly pulse corticosteroids during the study;
16. Receive immunisations with live vaccines or Ig treatments within one month prior SD 1 or need for such treatment during the study;
17. Participation in any interventional clinical trial within 2 months before SD 1 (or within 5 half-lives of the investigated compound before SD 1, whichever is longer), prior to SD1
18. Have moderate to severe renal impairment (creatinine clearance < 50 ml/min; according to Cockcroft-Gault equation);
19. Allergy or hypersensitivity to gadolinium;
20. Known hypersensitivity to atacicept or to any of the components of the formulated atacicept.
21. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD)
22. History or presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure;
23. History of cancer, except adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix;
24. Aspartate aminotransferase (AST) alanine aminotransferase (ALT) or alkaline phosphatase (AP) level >2.5 x ULN. Total bilirubin >1.5 x ULN at screening;
25. Clinically significant abnormality in any haematological test (e.g. haemoglobin < 100 g/L (6,21 mmol/L), WBC < 3*109/L, lymphocyte count <0.8*109/L, platelets <140*109/L) at screening;
26. Clinically significant abnormality on chest X-ray performed within 3 months before SD1 or on ECG performed at screening;
27. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatm;
1. History of ON prior to current ON attack;
2. Bilateral optic neuritis;
3. Diagnosis of MS;
4. Diagnosis of Devic’s disease;
5. Co-morbid ocular condition not related to optic neuritis (ascertained by detailed history and examination, including glaucoma, hypoplasia of the optic nerve, macular hole, vitreomacular traction, diabetes, or other diseases of the optic nerve);
6. Non-evaluable OCT at screening visit due to edema in the affected eye defined as follows:RNFL thickness more than 10 micrometer above normal in 2 or more sectors, or RNFL thickness greater than 200 micrometer in any of the 12 sectors;
7. Severe myopia superior to 5 diopters;
8. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments (such as, but not limited to, significant nervous system, renal, hepatic, endocrine or gastrointestinal disorders), which in the Investigator’s opinion constitutes a risk or a contraindication for the subject’s participation in the study or that could interfere with the study objectives, conduct or evaluation.
9. Prior treatment with B cell modulating therapies, such as rituximab or belimumab;
10. Prior exposure to immunomodulatory therapy, such as interferon beta or glatiramer acetate;
11. Prior exposure to immunosuppressive or cytotoxic agents including but not restricted to cladribine, mitoxantrone, alemtuzumab, cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, or natalizumab;
12. Prior myelosuppressive / cytotoxic therapy, such as lymphoid irradiation, or bone marrow transplantation;
13. Prior use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIg) or plasmapheresis;
14. Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 60 days prior to SD1 except the optional corticosteroid course to treat the initial ON event;
15. Require chronic or monthly pulse corticosteroids during the study;
16. Receive immunisations with live vaccines or Ig treatments within one month prior SD 1 or need for such treatment during the study;
17. Participation in any interventional clinical trial within 2 months before SD 1 (or within 5 half-lives of the investigated compound before SD 1, whichever is longer), prior to SD1
18. Have moderate to severe renal impairment (creatinine clearance < 50 ml/min; according to Cockcroft-Gault equation);
19. Allergy or hypersensitivity to gadolinium;
20. Known hypersensitivity to atacicept or to any of the components of the formulated atacicept.
21. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD)
22. History or presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure;
23. History of cancer, except adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix;
24. Aspartate aminotransferase (AST) alanine aminotransferase (ALT) or alkaline phosphatase (AP) level >2.5 x ULN. Total bilirubin >1.5 x ULN at screening;
25. Clinically significant abnormality in any haematological test (e.g. haemoglobin < 100 g/L (6,21 mmol/L), WBC < 3*109/L, lymphocyte count <0.8*109/L, platelets <140*109/L) at screening;
26. Clinically significant abnormality on chest X-ray performed within 3 months before SD1 or on ECG performed at screening;
27. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatm

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified