Safety and Preliminary Clinical Activity of Itolizumab in Dermatomyositis

Dermatomyositis, Adult Type Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Clinical Activity of Itolizumab in Subjects With Dermatomyositis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05986162
• Other study ID #: BPL-ITO-DM-1001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: December 30, 2023
• Est. completion date: June 25, 2025

Study information

• Verified date: August 2023
• Source: Biotech Pharmaceutical Co., Ltd.
• Contact: Xijuan Song
• Phone: 010-51571020
• Email: songxijuan[@]biotechplc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of Itolizumab in subjects with Dermatomyositis.

Description:

The study will enroll approximately 44 subjects in two parts:

Part 1 is an open label, 3+3 single dose escalation and then mutiple dose administration phase. 9~30 patients with DM are expected to be enrolled across 3 dose cohorts.

Part 2 is a randomized phase and will enroll approximately 14 additional subjects, randomized in a 1:1 ratio to one of the 2 doses based on efficacy data obtained from Part 1. All participants in this study will receive Itolizumab intravenously every two weeks for a total of 7 doses.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 44
• Est. completion date: June 25, 2025
• Est. primary completion date: May 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female subject aged 18-75 years old (inclusive).

2. Fulfill one of the following criteria for DM:1) Bohan and Peter criteria for definite or probable DM;2) ENMC 2018 Dermatomyositis Classification Criteria

3. Disease activity fulfills at least three of the following criteria:1) MMT-8 score < 142; 2) physician's global disease activity =2 cm; 3) patient's global activity =2 cm; 4) extra-muscular activity =2 cm; 5) Health Assessment Questionnaire [HAQ] =0.25; 6) at least one muscle enzyme >1.5 times ULN

4. Under treatment with corticosteroids and/or at least 1 immunesuppressant, and being on stable therapy for at least 4 and 8 weeks for corticosteroids and immunesuppressant respectively (see Section 5.7.1)

5. Fulfill all of the following criteria: 1) % predicted values of FVC=70%; 2) % predicted values of DLCO=60%; 3) chest HRCT indicating the extent of disease lesion of DM-ILD < 20% as determined by the investigator

6. Negative result of serum HCG within 72 hours before enrollment for female with potential fertility

7. Able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF)

Exclusion Criteria:

1. Subject with other connective tissue diseases (e.g., systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, Sjogren's syndrome, mixed connective tissue disease, etc.) or ANCA associated vasculitis.

2. Diagnosed with polymyositis or IMNM.

3. Diagnosed with systemic, severe musculoskeletal disorder that unrelated to DM and will interfere with the investigator's assessment of the subject's muscle strength.

4. Subject who plans to start a physical therapy program during the trial.

5. Subject who has a medical history of New York Heart Association class III or IV congestive heart failure, clinically significant or uncontrolled unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening

6. Subject with impaired renal function (serum creatinine > 1.5 x ULN or creatinine clearance < 30 mL/min [Cockcroft-Gault formula]) at screening.

7. Any of following significant abnormalities in liver function at screening:

1. Serum alanine transaminase (ALT) or glutathione transaminase (AST) = 3 x ULN, except when judged by the investigator to be due to DM;

2. Total bilirubin = 1.5 x ULN;

3. Cirrhosis classification of Child-Pugh grade C.

8. Any of the following abnormalities at screening:

1. Hepatitis B-related tests: ? positive hepatitis B surface antigen (HBsAg); ? positive hepatitis B core antibody (HBcAb); ? positive hepatitis B surface antibody (HBsAb) and no history of hepatitis B vaccination; ? positive hepatitis B e antigen or hepatitis B e antibody;

2. Positive hepatitis C virus nucleic acid test (HCV-RNA);

3. Positive acquired immunodeficiency syndrome antibody (HIV-Ab);

4. Positive anti-syphilis spiral antibody (TP-Ab);

5. Other acute or chronic infections requiring treatment.

9. Absolute lymphocyte count < 0.5×109/L at screening

10. Subject who has a medical history of tuberculosis or those who deny a history of tuberculosis but has a positive gamma-interferon release test at screening.

11. Any other clinically significant clinical condition or laboratory tests abnormality that, in the judgment of the investigator, may affect the safety evaluation

12. Any malignant tumor other than the cured carcinoma in situ or basal cell carcinoma within 5 years before screening

13. Suspected allergic to the investigational drug or any of its excipients

14. Subject who had participated in other clinical studies (other than those not receiving interventions, such as observational study or questionnaires survey) within 3 months prior to screening, or who are participating in other experimental treatments.

15. Subject who requires to be administrated with higher dose of corticosteroids and/or immunesuppressant than the allowed maximum dose specified in the protocol (section 5.7.1)

16. Subject who had been treated by one or more of the following drugs during the corresponding time window prior to screening:

1. cyclophosphamide, rituximab within 12 months prior to screening;

2. belizumab, tetrasip within 24 weeks prior to screening;

3. intravenous immunoglobulin injections, baliximab, infliximab, adalimumab, tolimumab, JAK inhibitors within 12 weeks prior to screening;

4. Other monoclonal antibodies or other biological agents within 12 weeks or 5 half-lives [whichever is longer] prior to screening.

17. Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment

18. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.

Related Conditions & MeSH terms

• Dermatomyositis
• Dermatomyositis, Adult Type

Intervention

Drug:
• Itolizumab
Patients to be treated with Itolizumab.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Biotech Pharmaceutical Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory indicators	To explore wether the change of the antibody can indcates the clinical efficiency of Itolizumab in DM patients	Study Week 16
Primary	Incidence of Treatment Emergent Adverse Events	Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0	Study Week 20
Secondary	Maximum serum concentration of Itolizumab, Cmax	Maximum serum concentration of Itolizumab	Study Week 16
Secondary	Minimum serum concentration of Itolizumab, Cmin	Minimum serum concentration of Itolizumab	Study Week 16
Secondary	Time to maximum serum concentration of Itolizumab, Tmax	Time to maximum serum concentration of Itolizumab	Study Week 16
Secondary	Total Itolizumab exposure across time, AUC0-t	Total Itolizumab exposure across time	Study Week 16
Secondary	Half life of Itolizumab, t1/2	Half life of Itolizumab	Study Week 16
Secondary	IL-2	Inflammatory Markers:IL-2	Study Week 16
Secondary	IL-6	Inflammatory Markers:IL-6	Study Week 16
Secondary	TNF-a	Inflammatory Markers: TNF-a	Study Week 16
Secondary	IFN-?	Inflammatory Markers:IFN-?	Study Week 16
Secondary	CRP	Inflammatory Markers:CRP	Study Week 16
Secondary	Serum ferritin	Inflammatory Markers:Serum ferritin	Study Week 16
Secondary	ESR	Inflammatory Markers:ESR	Study Week 16
Secondary	IgG	Inflammatory Markers:IgG	Study Week 16
Secondary	IgM	Inflammatory Markers:IgM	Study Week 16
Secondary	IgA	Inflammatory Markers: IgA	Study Week 16
Secondary	CD6 receptor expression levels	Mean change of CD6 receptor expression levels in relative to baseline	Study Week 16
Secondary	T cell subsets	Mean change of different proportion of T cell subsets in relative to baseline	Study Week 16
Secondary	Proportion of patients achieving a TIS of =20	Defined as patients with an increase of =20 points on the Total Improvement Score in relative to baseline.	Study Week 16
Secondary	Proportion of patients achieving DOI	DOI defined as = 20% improvement in 3 of any 6 core set measures, with no more than 2 core set measures worsening by = 25% (MMT-8 cannot worsen by = 25%).	Study Week 16
Secondary	Mean Change of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score	Defined as the mean change of activity score of CDASI(Score Range:0~132,The hingher score indcates the worse outcome) relative to baseline.	Study Week 16
Secondary	Incidence of ADA	Defined as the precentage of subjects presenting anti-drug antibody	Study Week 16