A phase I-II, randomized, double-blind, placebo-controlled, dose escalation study of Neovacs’ IFNa-Kinoid in adult subjects with Systemic Lupus Erythematosus. - IFN-Kinoid in Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 23 January 2017
• Main ID: EUCTR2009-012059-47-BE
• Date of registration: 05/01/2010
• Prospective Registration: Yes
• Primary sponsor: Neovacs SA
• Public title: A phase I-II, randomized, double-blind, placebo-controlled, dose escalation study of Neovacs’ IFNa-Kinoid in adult subjects with Systemic Lupus Erythematosus. - IFN-Kinoid in Systemic Lupus Erythematosus
• Scientific title: A phase I-II, randomized, double-blind, placebo-controlled, dose escalation study of Neovacs’ IFNa-Kinoid in adult subjects with Systemic Lupus Erythematosus. - IFN-Kinoid in Systemic Lupus Erythematosus
• Date of first enrolment: 28/01/2010
• Target sample size: 28
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012059-47
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, France, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Diagnosis of SLE according to current American College of Rheumatology
(ACR) criteria (4 of 11 ACR criteria),
2. SLEDAI =4 and =10,
3. Positive Anti-nuclear Antibodies (ANA) and/or Positive anti-dsDNA
antibodies at the time of screening,
4. Male or female between 18 and 50 years of age included at the time of the first
planned administration of the study drug,
5. Current immunity to measles, mumps, rubella and varicella, as evidenced by
positive IgG titers at the time of screening,
6. For subjects recruited during local influenza season, current vaccination
against seasonal influenza at least 7 days prior to randomiza7. Vaccination against H1N1 influenza at least 7 days prior to randomization, if
judged indicated by the Investigator. The nasal spray form of the vaccine is
not acceptable as it is a live attenuated vaccine,
8. For subjects with reproductive potential (males and females), use of a reliable
means of contraception (e.g., hormonal contraceptive, patch, vaginal ring,
intrauterine device, or other barrier method of contraception) throughout their
participation in the study, (i.e. until study Day 168 (Month 6 study visit),
unless additional extended follow up visits are needed in the presence of
persisting anti-IFNa antibodies. In this case, contraception must be continued
until anti-IFNa antibody levels are back to baseline and further follow visits
are no longer required,
9. According to the Investigator, able and willing to comply with the
requirements of the study protocol (e.g., completion of the diary cards, return
for follow-up visits),
10. Written informed consent obtained from the subject.

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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any serious manifestation of lupus at entry, that, in the opinion of the investigator is likely to require initiation of off-protocol medication changes during the course of the study and in particular no BILAG A score,
2. Any non-SLE manifestation likely to require, in
the investigator's judgment, treatment with highdose corticosteroids or the addition of an immunosuppressive regimen during the course of the trial,
3. Received > 20 mg/day of prednisone, or equivalent, for > 7 days during the 30 days prior to screening,
4. Currently receiving or having received pulse dose corticosteroids or intravenous immunoglobulin (IVIg) within 3 months prior to screening,
5. Received cyclophosphamide within 3 months prior to screening,
6. Received a monoclonal antibody during the 6 months prior to screening,
7. Previously received an investigational treatment directed against IFN alpha ,
8. Received B-cell depleting therapy (e.g. Rituximab) within 12 months prior to screening,
9. Received IV antibiotics during the 30 days prior to screening,
10. Significant electrocardiogram (ECG) abnormalities that are clinically relevant and
preclude study entry according to the Investigator’s opinion,
11. Evidence of any clinically significant abnormality on a chest X-ray which, in the opinion of the investigator could represent active infection, latent tuberculosis or treatable manifestation of lupus,
12. Any laboratory abnormality that is clinically relevant and precludes study entry according to the Investigator’s opinion, in particular subjects with already impaired functions of central organs at screening (e.g. AST > 2.5 x upper limit of the norm (ULN), ALT > 2,5 x ULN, creatinine > 1,5 x ULN, serum potassium above or below the
normal range, hemoglobin < 8g/dL, WBC < 1,800/mm3, neutrophils < 1,500/mm3, platelet count < 50,000/mm3, lupus with central manifestation) should be excluded from the study.
13. History of malignancy except completely excised basal cell carcinoma,
14. Congenital immune deficiency,
15. Positive IgM antibody titers in the presence of negative IgG titers to Epstein-
Barr virus (EBV) or cytomegalovirus (CMV),
16. Frequent recurrences of oral or genital herpes simplex lesions (= 6 / year),
17. Episode of shingles within one year of screening,
18. Human Immunodeficiency Virus (HIV), hepatitis C virus (HCV) or HBV (HBsAg, anti-HBc ab) positive,
19. Any current signs or symptoms of infection at entry,
20. Administration of any live vaccine within the 3 months prior to study entry (e.g. oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin vaccine),
21. Planned use of any investigational or non-registered product (drug or vaccine)
other than the study product within 30 days preceding the first dose of study product, or during the study period,
22. History of severe allergic or anaphylactic reactions to any component of the
kinoid and/or seafood,
23. Pregnancy or lactation,
24. History of chronic alcohol consumption and/or drug abuse within 6 months of
screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus (SLE)
MedDRA version: 14.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: IFN-a2b Kinoid
Product Code: IFN-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not assigned yet
Current Sponsor code: IFN-K DS
Other descriptive name: IFN-a 2b Kinoid Drug Substance
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: range
Concentration number: 350-450
Pharmaceutical form of the placebo: Emulsion for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Primary end point(s): Safety endpoints:

• Occurrence, intensity and relationship to IFN-K immunization of any solicited local and general signs and symptoms during a 7-day follow up period (i.e. Day of study drug administration and 6 subsequent days) after each IFN-K dose.
• Occurrence, intensity and relationship to IFN-K immunization of unsolicited local and general signs and symptoms occurring throughout the study period.
• Occurrence and relationship to IFN-K immunization of all serious adverse events (SAE) occurring throughout the study period.
• Occurrence, intensity and relationship to IFN-K immunization of any abnormality in physical examination, vital signs, 12-lead ECG, clinical laboratory evaluations, and adverse events (AEs).

Secondary Objective: The secondary objectives will be:
- To evaluate the anti-IFNa antibody response induced by IFN-K.
- To evaluate the neutralizing antibody response induced by IFN-K.
- To evaluate the cellular immune response in vitro.
- To assess the levels of serum auto-antibodies.
- To evaluate changes in the expression of IFNa inducible genes in peripheral blood
mononuclear cells (PBMCs) in all subjects and in subjects with a positive IFN
signature at baseline.
- To evaluate the levels of IFNa inducible serum chemokines.
- To evaluate the clinical response by assessing:
• Disease activity using:
o The SLE Disease Activity Index (SLEDAI).
o The British Isles Lupus Assessment Group (BILAG) index.
o The Physician Global Assessment (PGA)
o The SELENA-SLEDAI Flare Index
• Quality of life using the SF-36 health care questionnaire.

Main Objective: The primary objective of this trial is to assess the safety and tolerability of three
administrations of IFN-K adjuvanted with ISA-51 at four doses (30, 60, 120 or 240 mcg), given on SD0, SD7 and SD28 (+/- a fourth dose on SD84 [Month 3]) in adult subjects with SLE.

Secondary ID(s)

IFN-K-001