| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012503 |
| E.1.2 | Term | Dermatomyositis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To assess the safety and tolerability of IMO-8400 in adult patients with active dermatomyositis (DM)
• To assess the effect of IMO-8400 on the cutaneous manifestations of DM |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1 Has signed the current, approved Informed Consent Form
2 Is 18 to 75 years of age (inclusive) at the time of consent
3 Has definite or probable DM based on the criteria of Bohan and Peter (Appendix 3; 1975a, 1975b) OR those patients who have all other definite or probable Bohan and Peter criteria but do not have heliotrope rash and Gottron’s signs/papules may still be included if they have one or more of the following:
a) DM autoantibody (anti-Mi-2, anti-MDA5, anti-TIF1-gamma, anti-NXP-2, anti-Jo-1, anti-PL-12, anti-PL-7, anti-EJ, anti-KS, anti-OJ); at least 1 autoantibody must be present and documented in the patient’s medical record
b) A classic DM associated skin change including at least one of the following: malar rash without sparing nasolabial folds, Shawl sign, V neck rash, periungal erythema, or mechanic’s hands; documented in the patient’s medical record
4 Has a CDASIv2-Activity score ≥15 at Visit 2 (Baseline)
5 Patients with muscle weakness are eligible; however, having muscle weakness is not mandatory. These patients have documented assessment of active muscle involvement as described in the protocol
6 If on permitted concomitant medications at Screening, the therapy regimen can include one or more of the following:
a) Stable dose of prednisone (or other oral equivalent) ≤20 mg/day (or ≤140 mg/week) for ≥4 weeks
b) Stable regimen that does not exceed the approved dosages for ≥12 weeks of no more than 1 of the following non-steroidal immunomodulatory medication(s): intravenous immunoglobulin, mycophenolate mofetil, cyclophosphamide, cyclosporine, leflunomide, tacrolimus, methotrexate,
azathioprine
c) Stable regimen of topical treatments for scalp involvement for ≥3 weeks
7 Study participants must have a diagnostic evaluation for cancer if the diagnosis of DM was within 2 years prior to the Screening Visit. The evaluation should include either:
a) All age- and gender-appropriate screening tests and a computed tomography (CT) of the chest, abdomen, and pelvis; OR
b) Positron emission tomography and computed tomography (PET/CT) of the chest, abdomen, and pelvis
Note: If a diagnostic evaluation for cancer has not been performed within 2 years prior to the Screening Visit in patients for whom it is required, either a CT of the chest, abdomen, and pelvis should be performed, or a PET/CT of the chest, abdomen, and pelvis if this is standard practice in the
particular center. The diagnostic evaluation for cancer must be normal for a patient to meet this inclusion criterion
8 Study participants must have no evidence of active or latent TB after a diagnostic evaluation with a chest x-ray OR chest CT (CT) and 1 of the following: a) a purified protein derivative skin test, b) a QuantiFERON blood test or c)T-SPOT.TB blood test.
If the diagnostic evaluation has not been performed within 12 weeks of the Screening Visit, it may be performed during the Screening Period (performed per Center for Disease Control guidelines. For the patient to be eligible, the result of the diagnostic evaluation should include a negative chest image and 1 of the following: a) a PPD skin test with ≤5-mm induration, or b) a negative (not detected) QuantiFERON result or c) a negative T-SPOT.TB blood test. If the QuantiFERON result is indeterminate, the test may be repeated once. If the second or repeat QuantiFERON test result is indeterminate, then a PPD skin test result may be used to determine patient eligibility. The PPD skin test is not an acceptable method of TB testing in Sweden.
9 Women of childbearing potential and men must agree to use effective contraceptive methods from Screening throughout the study and until at least 4 weeks after the last dose of study drug
10 Agrees to use a broad-spectrum (UVA/UVB) sunscreen with an SPF ≥15 daily (or a water-resistant, broad spectrum sunscreen with an SPF ≥30 for extended outdoor activity), and to not increase their normal sun exposure during the course of this study
11 Is willing and able to comply with this protocol |
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| E.4 | Principal exclusion criteria |
1. Has ongoing severe dysphagia (e.g., requires a feeding tube) for the 3 months prior to Screening
2. Has known hypersensitivity to any oligodeoxynucleotide
3. Has a history of drug abuse within one year of screening, or evidence of drug abuse by urine drug screening
4. Has a history of alcohol abuse within one year of screening
5. Is pregnant (or intends to become pregnant within 6 months of last dose of study medication) or nursing
6. Has body weight >140 kg
7. Has any one of the following hepatitis serologic test results:
a) Positive hepatitis B surface antigen test (HBsAg), or
b) Positive hepatitis B core antibody test (anti-HBc) AND negative hepatitis B surface antibody (anti-HBs), or
c) Positive hepatitis C virus antibody test (anti-HCV)
8. Has evidence of seropositive test in the patient’s medical records or is currently receiving treatment for human immunodeficiency virus (HIV)-1 or HIV-2
9. Has screening safety laboratory test meeting any of the following criteria:
a) Hemoglobin <10.5 g/dL
b) White blood cell (WBC) count <3000/mm3
c) Absolute neutrophil count (ANC) <1.5 x 109/L (1500/mm3)
d) Platelet count <100,000/mm3
e) Serum creatinine >1.2 mg/dL in female patients and >1.5 mg/dL in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study if their eGFRs are >60 mL/min
f) Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) >5 times ULN (unless considered consistent with muscle origin and accompanied by gamma-glutamyl transferase (GGT) <1.5 times ULN)
g) Total bilirubin >1.5 times ULN
h) Prothrombin time (PT) >1.5 times ULN
i) C3 or C4 <LLN
j) A:G ratio <LLN
k) Urinalysis with proteinuria >1+
10. Has a diagnosis of Juvenile DM, IBM, drug-induced toxic myopathy, metabolic myopathy, dystrophy, cancer-associated DM , or connective tissue disease-associated DM (e.g., overlap syndrome)
11. Has received one or more of following prohibited treatments within the interval noted prior to Screening (Visit 1):
a) Rituximab within 24 weeks (Note: patients who received rituximab are only eligible for inclusion if B-cell counts are confirmed to be within normal limits)
b) Intravenous corticosteroids within 12 weeks
c) Intravenous immunosuppressive drugs within 12 weeks
d) Any other monoclonal antibody, biologic agent, or investigational agent within 12 weeks or 5 half-lives (whichever is longer)
e) Antimalarials (e.g., hydroxychloroquine) within 36 weeks
f) Topical corticosteroids (excluding scalp) within 2 weeks
12. Has evidence of or has required treatment for cancer (except for treated, non-invasive carcinoma of the skin or cured carcinoma-in-situ following discussion with Medical Monitor ) within 5 years
13. Has other chronic or active significant medical conditions within 6 months prior to Screening including but not limited to: allogeneic organ transplant (e.g., solid organ, bone marrow, or stem cells); cardiac disease (e.g., unstable angina, myocardial infarction, ventricular arrhythmia); congestive heart failure; liver disease; neurological disease; hematological disease; kidney disease; uncontrolled seizure disorder; uncontrolled pulmonary disease; uncontrolled gastrointestinal disease; uncontrolled endocrinological disease; uncontrolled psychiatric disease; or uncontrolled diabetes mellitus
14. Has interstitial lung disease requiring the use of supplemental oxygen
15. Has received or is expected to receive any live viral or bacterial vaccination within 3 months prior to Screening
16. Has received a Bacille Calmette-Guerin (BCG) vaccination within 12 months of Screening or is expected to receive it during the course of the study
17. Has a history of or ongoing active, chronic, or recurrent infection (including bacterial, viral, parasitic, protozoal, and/or fungal/granulomatous infections [e.g., histoplasmosis, coccidioidomycosis, aspergillosis]) requiring treatment with systemic antimicrobials, antivirals, antiparasitics, antiprotozoals, or antifungals within 12 weeks prior to Screening, or serious infection (including but not limited to pneumonia, sepsis, bone or joint infection) requiring hospitalization or treatment with IV antibiotics within 12 weeks prior to Screening
18. Has a history of opportunistic infection or non-tuberculosis mycobacterial infection within 9 months prior to Screening
19. Has any other condition that would, in the opinion of the Investigator, potentially compromise the safety or compliance of the patient or preclude the patient’s successful completion of the study
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Safety and Tolerability Endpoints
•Number of patients discontinuing treatment due to AEs
•Frequency and severity of AEs
•Physical examination findings, including vital signs
•Standard laboratory safety tests including hematology, chemistry, coagulation and urinalysis
•Assessment of ISRs
•ECG findings
•Laboratory safety assessments including CH50, C3, C4, troponin, CRP, albumin, globulin, A:G ratio, proteinuria, eGFR, and platelet count
Primary Efficacy Endpoint
•Change from baseline in mCDASIv2 Activity score
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and Tolerability Endpoints:
AEs reported and observed, assessment of ISRs, Vital Signs: weekly during Week 1 to Week 25, then at end of study visit on Week 29
Physical examination findings standard laboratory safety tests, ECG, laboratory safety assessments: every four weeks during Week 1-Week 25, then at end of study visit on Week 29
Efficacy Endpoint:
CDASIv2: every four weeks during Week 1-Week 25. |
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| E.5.2 | Secondary end point(s) |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, immunogenicity |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Czech Republic |
| Hungary |
| Sweden |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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