Phase IIa exploratory study to assess the safety and effect of IFNa-Kinoid (IFN-K) in adult patients with Dermatomyositis

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2016-000137-52-DE
• Date of registration: 06/06/2016
• Prospective Registration: Yes
• Primary sponsor: Neovacs SA
• Public title: Phase IIa exploratory study to assess the safety and effect of IFNa-Kinoid (IFN-K) in adult patients with Dermatomyositis
• Scientific title: A Phase IIa, Single Blind, Randomized, Study to Evaluate the Safety, the Immunogenicity, and the Clinical and Biological Efficacy of IFNa-Kinoid (IFN-K) in Adult Subjects with Dermatomyositis.
• Date of first enrolment: 26/07/2016
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000137-52
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Switzerland, United Kingdom

Contacts

• Name: Regulatory Affairs
• Affiliation: Neovacs SA

• Name: Regulatory Affairs
• Affiliation: Neovacs SA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Has provided written informed consent
2. Patient newly diagnosed or relapsing with “definite” or “probable” dermatomyositis based on ENMC criteria (2004)
3. Patient with an MMT-8 =120 and/or an MMT-5 =22
4. Patient:
•requiring corticosteroids (CS) at a dose of 1 mg/Kg or = 70 mg of prednisone equivalent/day
•or currently receiving CS at a dose of 1 mg/Kg or = 70 mg of prednisone equivalent/day for less than 2 weeks at the time of screening visit
5. Must have a muscle biopsy if not performed within 1 month at the time of screening visit
6. Is a male or female, aged between 18 and 65 years, inclusive, at the time of the screening visit
7. Study patient and his/her partner has to use effective method of contraception for the duration of the study including the Extended Follow-up period
Note: If of child-bearing potential, effective contraception methods include:
i. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first planned administration of the study product. In case of oophorectomy alone, the reproductive status of the woman must be confirmed by follow-up hormone level assessment.
ii. Male sterilization (at least 6 months prior to Screening).
iii. Combination of the following:
•Oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
•Or Placement of an intrauterine device (IUD) or intrauterine system (IUS)
•AND Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)
A combination of the use of condoms and the use of oil and grease containing chemical contraceptives (vaginal suppositories, tablets, gel) is not recommended, as the grease and oil might affect the condom and cause it to leak, and therefore reduces the contraception safety (pearl index not below 1%).
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago prior screening visit. In the case of oophorectomy alone, women are considered not of child bearing potential only when their reproductive status have been confirmed by follow-up hormone level assessment.
8. Is able and willing to comply with the requirements of the study protocol (e.g. completion of the diary cards, return for follow-up visits), in the opinion of the investigator.
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 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Is high-risk human papilloma virus (HPV) positive by reverse transcription polymerase chain reaction (RT-qPCR) on a cervical swab at Screening or within 3 months prior to the first planned study product administration
2. Has cytological abnormalities = HSIL on a cervical swab at Screening or within 3 months prior to the first planned study product administration
3. Is positive for autoantibodies anti-NXP2, TIF1?, MDA5 or anti-synthetase antibodies
4. Is positive for any malignancy documented at the time of screening visit, i.e. by biological markers, images*, biopsies* or endoscopies*
*note: please refer to study flow chart for acceptable window period for previous exams
5. Has a history of any malignancy except than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry
6. Has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
7. Has preexisting severe cardiac or pulmonary conditions
8. Has received IV pulse dose CS (= 250 mg prednisone equivalent/day) within 3 months prior to the first planned administration of the study product
9. Has received intravenous immunoglobulin (IVIg) within 4 months before the first administration of the study product
10. Has received potent immunosuppressive drugs such as cyclophosphamide, methotrexate, azathioprine, mycophenolate, cyclosporine A, oral tacrolimus within 12 months prior to the first planned administration of the study product
11. Has received abatacept, anifrolumab, belimumab, TNF antagonists or another registered or investigational biological therapy within 12 months prior to the first planned administration of the study product
12. Has received anti-B-cell therapy (e.g. rituximab, epratuzumab) within 12 months prior to the first planned administration of the study product
13. Has received any live vaccine within 3 months prior to the first planned administration of the study product (e.g. nasal flu vaccine, oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, Japanese encephalitis vaccine, dengue vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin [BCG] vaccine, oral typhoid vaccine)
14. Has used any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, or any investigational or non-registered vaccine within 30 days prior to the first planned administration of the study product
15. Has significant electrocardiogram (ECG) abnormalities other that consistent with dermatomyositis that are clinically relevant and preclude study eligibility in the investigator’s opinion
16. Has inflammatory joint or skin disease other than dermatomyositis that may interfere with study assessments
17. Has frequent recurrences of oral or genital herpes simplex lesions
(= 6 occurrences during the 12 months prior to first study product administration)
18. Has had an episode of shingles during the 12 months prior to

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

Health Condition(s) or Problem(s) studied

Dermatomyositis
MedDRA version: 19.1 Level: PT Classification code 10012503 Term: Dermatomyositis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: IFNa-Kinoid
Product Code: IFN-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not yet assigned
Current Sponsor code: IFN-K DS
Other descriptive name: IFN-Kinoid Drug Substance
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 380-
Pharmaceutical form of the placebo: Emulsion for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: •To assess the safety of IFN-K emulsified with ISA 51 VG
•To assess the immune response (anti-IFNa neutralizing antibody at Week 24 & W48))
•To assess the biological efficacy (change from baseline of the expression of IFN induced genes at W24 & W48)
•To assess the clinical response as measured by the clinical disease activity at W24 & W48:
-Manual Muscle Testing MMT 8 and MMT 5
-Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
-Physician’s Global Activity
-Patient Global Activity
-Accelerometer to measure patients activity levels
-Quality of Life Questionnaires (HAQ and DLQI)
-Changes in DM therapy
•To evaluate the immune response:
-Anti-IFNa antibody
-Anti-KLH antibody

Exploratory Objectives
•To assess biological parameters:
-Neutralizing capacity against IFNa subtypes
-Anti-IFNa and anti-KLH antibody isotyping
-IFNß cross-neutralization
•IFN gene signature in muscle and skin biopsies
•Histopathological features of muscle and skin biopsies

Timepoint(s) of evaluation of this end point: Cohort 1: at Week 16.
Cohort 2: at Week 48.

Main Objective: Cohort 1: the primary objective of this cohort is to evaluate the immune response induced by IFN-K as measured by the production of anti-IFNa neutralizing antibody at Week 16.
Cohort 2: the primary objectives of this cohort are to evaluate the down regulation of IFN-induced gene following IFN-K treatment at Week 48, taking into account the IFN-gene signature at baseline.

Primary end point(s): Cohort 1: production of anti-IFNa neutralizing antibody at Week 16.
Cohort 2: change from baseline in the expression of IFN-induced genes at Week 48 in blood.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Safety Endpoints: throughout the study period
Biological secondary End point: at Week 24 and Week 48
Clinical secondary Endpoints: at Week 0, Week 12, Week 24, Week 36 and Week 48
Immunogenicity secondary Endpoints: At timepoints specified on the flow chart

Secondary end point(s): Safety Endpoints
• Occurrence, intensity and relationship of any solicited local and systemic AEs during a 7-day follow-up period (i.e. day of study product administration and 6 subsequent days) after each IFN-K or placebo dose
• Occurrence, intensity and relationship of unsolicited local and systemic AEs occurring throughout the study period
• Occurrence and relationship of all SAEs occurring throughout the study period
• Occurrence and intensity of solicited injection site reactions 1 hour post study product administration
• Occurrence and intensity of solicited systemic reactions 1 hour post study product administration
• Hematological and biochemical results within or outside the normal ranges and percent change from baseline at each visit
• Occurrence, intensity and relationship of any abnormality in physical examination, vital signs, 12-lead ECG, clinical laboratory evaluations
• Rate and severity of viral infections
• Occurrence of cancers

Biological secondary End point
• Production of anti-IFNa neutralizing antibody at W24 and W48
• Change from baseline in the expression of IFN-induced genes at W24 and W48 in blood

Clinical secondary Endpoints
• Response to treatment with IFN-K, as measured by Muscle Strength Testing-MMT 5 and MMT 8 at W0, W12, W24, W36 and W48
• Response to treatment with IFN-K, as measured by Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) at W0, W12, W24, W36 and W48
• Evaluation of clinical response by assessing disease activity using: Patient Global Activity
• Evaluation of clinical response by assessing disease activity using: Physician Global Activity
• Response to treatment with IFN-K as measured by an accelerometer at W0, W12, W24, W36 and W48.
• Changes from baseline in the HAQ-DI score at W0, W12, W24, W36 and W48
• Changes from baseline in the DLQI score at W0, W12, W24, W36 and W48
• Scores and incidence of patient requiring change in DM therapy (intensification and/or addition of drugs)

Immunogenicity secondary Endpoints
At timepoints specified on the flow chart, Geometric Mean Titers (GMT) and seroconversion rates for:
• Anti-IFNa binding antibody titers
• Anti-IFNa neutralizing antibody titers
• Anti-KLH binding antibody titers

Exploratory Endpoints
• Evaluation of biological response by assessing:
-Neutralizing Anti-IFNa antibodies towards IFNa subtypes
-Anti-IFNa and anti-KLH antibody isotyping
-IFNß cross neutralization
• IFN gene signature in muscle and skin biopsies
• Histopathological features of muscle and skin biopsies.

Secondary ID(s)

IFN-K-005-DM

Source(s) of Monetary Support

Neovacs SA

Ethics review

Status: Approved
Approval date: 26/07/2016
Contact: