A placebo-controlled study to evaluate the efficacy, safety and tolerability of PF-06823859 in adult subjects with Dermatomyositis
- Conditions
- DermatomyositisMedDRA version: 20.0Level: PTClassification code 10012503Term: DermatomyositisSystem Organ Class: 10040785 - Skin and subcutaneous tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-004228-41-HU
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 76
STAGE 1 and 2:
3. Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score, v2-a (See Appendix 2) (Activity =14, and have failed at least 1 standard of care systemic treatment, (eg, corticosteroids).
5. Participant has had a standard work up for dermatomyositis (prior to) baseline.
a. Stable interstitial lung disease related to DM that is not severe in the opinion of the investigator is allowed, ie, no supplemental oxygen permitted.
b. If their DM diagnosis is within 2 years of the screening visit, then they must have completed either:
• Age appropriate malignancy screening eg, computerized tomography, (CT) of the chest/abdomen/pelvis if indicated; or
• PET CT of chest/abdomen/pelvis at least once by the baseline visit.
6. Willing to provide 6 skin punch biopsies; (4) skin punch biopsies at pre-dose Day 1, Visit 2, and (2) skin punch biopsies at Week 12.
7. Male participants able to father children and female participants of childbearing potential must agree to use 2 highly effective methods of contraception throughout the duration of the study, including the follow-up period until the end of study.
8. Female participants of non-childbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female participants (including female participants with tubal ligations) are considered to be of childbearing potential.
Amended STAGE 2:
If a participant meets eligibility for both the Stage 2, (skin focused cohort) and the Stage 3, (muscle disease cohort) the patient should be placed in the Stage 3 muscle disease cohort.
All inclusion criteria is the same as Stage 1 and Stage 2 with the exception to Inclusion Criteria #6.
6. Willing to provide at least (8) vs. 6 skin punch biopsies; (4) skin punch biopsies at pre-dose Day 1 Visit 2, (2) skin punch biopsies at Week 12, Visit 6 and (2) skin punch biopsies at Week 24 Visit 9.
STAGE 3:
3. Meets one of the following two criteria:
• MMT-8 = 136/150 and PhGA, VAS = 3 cm (0-10 cm) by visual analog scale (VAS) (Appendix 21)
• Sum of PhGA, VAS, PtGA, and extramuscular global assessment VAS scores (Appendix 20) is = 10 cm (0-10 cm) VAS for each)
4. Participant has failed at least two or more adequate courses of an immunosuppressive agent or immunomodulatory agent, including IVIG, at a dose known to be effective for rheumatologic diseases.
5. Participant has had a standard work up for dermatomyositis (prior to) baseline.
a. Stable interstitial lung disease related to DM that is not severe in the opinion of the investigator is allowed, ie, no supplemental oxygen permitted. completed either:
• Age appropriate malignancy screening eg, computerized tomography, (CT) of the chest/abdomen/pelvis if indicated; or
• PET CT of chest/abdomen/pelvis at least once by the baseline visit.
6. Male participants able to father children and female participants of childbearing potential must agree to use 2 highly effective methods of contraception throughout the duration of the study, including the follow-up period until the end of study.
7. Female participants of non-childbear
STAGE 1 AND STAGE 2:
2. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
7. Abnormal labs:
• Hemoglobin <10 g/dL;
• Neutrophils <1.0 x 109/L;
• Lymphocytes <500 cells/uL;
• Platelets <75 x 109/L;
• Creatinine clearance <60 ml/min according to modified Cockcroft-Gault equation;
• Alkaline phosphatase >2.5 x upper normal limit;
• Total bilirubin =1.5 x upper limit of normal.
Note: Elevation of aspartate aminotransferase (AST), alanine aminotransferase(ALT), lactate dehydrogenase (LDH) , creatinine kinase (CK) or aldolasedue to muscle involvement (in the opinion of the investigator) are allowed if gamma glutamyl transferase, GGT <1.5 upper limit normal.
12. Have received the following within 60 days of Day 1:
• Any intra muscular (IM) or IV steroid injection.
• Tofacitinib or any other Janus kinase (JAK) inhibitors.
• Any change in dose of an immunosuppressive/immunomodulatory or antimalarial agent. Dose must be stable for 60 days prior to Day 1 and remain stable through Week 12.
• Inhaled immunosuppressive agents can be used during the study however must be on a stable dose 60 days prior to Day 1 and remain stable through Week 12. (Immunosuppressive ophthalmic drops are allowed without any restrictions).
• Disease -modifying antirheumatic drugs (DMARD)s, (methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide). Less frequently used medications include gold salts, azathioprine, and cyclosporine. Dose must be stable for 60 days prior to Day 1 and remain stable through Week 12.
• Participants may be on one of the following cytotoxic agents: methotrexate, azathioprine, leflunomide, mycophenolate, or 6 MP, but not on any combination of these cytotoxic agents.
Use of IV or IM antibacterials, antivirals, antifungals, or anti-parasitic agents within 60 days of Day 1. Substitution of IM agents for oral agents because of gastro intestinal, (GI) intolerance may be acceptable, as long as it does not otherwise meet the criteria for a serious infection (requires hospitalization or use of other IV antibiotics) (See exclusion #24).
25. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) or any history of significant cerebrovascular disease within 24 weeks of screening. A screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or brady- arrhythmias) or that is indicative of serious underlying heart disease Wolff-Parkinson-White syndrome).
26. Have cancer or a history of cancer within 5 years of screening (other than adequately treated cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence within the previous 5 years).
Amended STAGE 2:
All exclusion criteria is the same as Stage 1 and Stage 2 with the exception of Exclusion Criterion #7 Abnormal labs and Exclusion Criterion #12
Exclusion Criterion #7:
• Hemoglobin <9 g/dL;
• Creatinine clearance <50 mL/min according to modified Cockcroft-Gault equation.
Exclusion Criterion #12:
• Any change in dose of an immunos
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method