No

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2018-000305-23-HU
• Date of registration: 28/11/2018
• Prospective Registration: Yes
• Primary sponsor: Boston Pharmaceuticals, Inc.
• Public title: No
• Scientific title: A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
• Date of first enrolment: 07/02/2019
• Target sample size: 156
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000305-23
• 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; 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

Argentina, Bulgaria, Colombia, Georgia, Hungary, Mexico, Peru, Philippines, Poland, Romania, Ukraine, United States

Contacts

• Name: Kathleen V. Murphy
• Affiliation: Boston Pharmaceuticals, Inc.

• Name: Kathleen V. Murphy
• Affiliation: Boston Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men and women, ages 18 to 70 years, inclusive
2. Patients must be mentally capable of giving consent and there must be evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study
3. Patients must have SLE as defined by meeting 4 of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE (with at least 1 clinical and 1 immunologic criterion OR Lupus nephritis as the sole clinical criterion in the presence of antinuclear antibodies [ANA] or anti- double-stranded deoxyribonucleic acid [dsDNA] antibodies), either sequentially or simultaneously
4. At screening, patients must have at least 1 of the following:
a. Elevated ANA = 1:80 via immunofluorescent assay at the central laboratory
b. Positive anti-dsDNA or anti-Smith (Sm) above the normal level as determined by the central laboratory
c. C3 or C4 levels below normal as determined by the central lab
5. At screening, the SLEDAI-2K must be = 6, including points from at least 1 of the following clinical components:
a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis
i. Excluding parameters which require central laboratory results: (hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia)
ii. Points from lupus headache and organic brain syndrome will also be excluded
6. On Day 0, the SLEDAI-2K must be = 6, including points from at least 1 of the following clinical components:
a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis
i. Excluding parameters which require central laboratory results: hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia
ii. Points from lupus headache and organic brain syndrome will also be excluded
7. Patients must have at least 1A or 2Bs from the following manifestations of SLE, as defined by the BILAG criteria as modified for use in this study, which must be confirmed by the central data reviewer:
a. BILAG A or B score in the mucocutaneous body system
b. BILAG A or B score in the musculoskeletal body system due to active polyarthritis
If only one “B” and no “A” score is present in the mucocutaneous body system or in the musculoskeletal body system due to arthritis, then at least 1 “B” must be present in the other body systems for a total of 2 “B” BILAG body system scores
8. Patients must be currently receiving at least 1 of the following:
a. Administration for a minimum of 12 weeks, and a stable dose for at least 56 days (8 weeks prior to signing consent) of the following permitted steroid-sparing agents: i. Azathioprine (AZA), mycophenolate mofetil or mycophenolic acid, chloroquine, hydroxychloroquine, or methotrexate (MTX)
b. Prednisone (or prednisone-equivalent) cannot exceed 30 mg/day at screening for a patient to be eligible and must be stable at a maximum of 10 mg/day for at least 5 days prior to Day 0 (randomization)
9. Women of childbearing potential:
a. Must have a negative serum pregnancy test at screening. Urine pregnancy test must be negative prior to first dose
b. Must not be breastfeeding
c. Must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of study drug BOS161721 plus 30 days (duration of ovulatory
Exclusion criteria:
1. Drug-induced SLE, rather than “idiopathic” SLE
2. Other systemic autoimmune disease
a. RA-Lupus overlap and secondary Sjögren syndrome are allowed
3. Any major surgery within 6 weeks of study drug administration, (Day 0), or any elective surgery planned during the course of the study
4. Any history or risk for TB, specifically those with:
a. Current clinical, radiographic, or laboratory evidence of active TB
b. History of active TB
c. Latent TB defined as positive QuantiFERON-TB Gold In-Tube (QFT-G) or other diagnostic test in the absence of clinical manifestations. Latent TB is not excluded if the patient has documented completion of adequate course of prophylactic treatment with regimen recommended by local health authority guideline, or the patient has started treatment with isoniazid, or other regimen recommended by local health authority guidelines for at least 1 month before Day 0 and continues to receive the prophylactic treatment during study until the treatment course is completed
5. Active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria, with the exception of mononeuritis multiplex and polyneuropathy, which are allowed
6. Severe proliferative lupus nephritis, which requires or may require induction treatment with cytotoxic agents or high dose CS
7. Concomitant illness that, in the opinion of the investigator, is likely to require additional systemic glucocorticosteroid therapy during the study, is exclusionary
a. However, treatment for asthma with inhalational CS therapy is allowed
8. Use or planned use of concomitant medication outside of standard of baseline treatment for SLE from Day -1 or for any time during the study
9. Active and clinically significant infection within 60 days prior to first dose of study drug. Clinically significant is defined as requiring systemic parenteral antibiotics or hospitalization
10. A history of opportunistic infection, or a history of recurrent or severe disseminated herpes zoster or disseminated herpes simplex within the last 3 years
11. Chronic viral hepatitis including hepatitis B and hepatitis C unless patient received curative treatment for HCV and has a documented negative viral load, known human immunodeficiency virus, or acquired immunodeficiency syndrome (AIDS)-related illness
12. Cryptosporidium in the stool sample at screening
13. White blood cells (WBC) < 1,200/mm3 (1.2 × 109/L) at screening
14. Absolute neutrophil count (ANC) < 500/mm3 at screening
15. CD4+ count < 350/µL at screening
16. Platelets < 50,000/mm3 (50 × 109/L) or < 35,000/ mm3 (35 × 109/L) if related to SLE, at screening
17. Hemoglobin < 8 g/dL or < 7 g/dL at screening if related to SLE
18. Proteinuria > 3.0 g/day (3000 mg/day) at screening or equivalent level of proteinuria as assessed by protein/creatinine ratio (3 mg/mg or 339 mg/mmol)
19. Serum creatinine > 2.0 mg/dL at screening or creatinine clearance (CrCL) < 40 ml/minute based on Cockcroft-Gault calculation
20. Serum alanine aminotransferase and/or serum aspartate aminotransferase > 2 × the upper limit of normal at screening, unless explicitly related to lupus based on the investigator’s judgment
21. Creatinine kinase > 3.0 × ULN at screening unless related to lupus myositis
22. Direct bilirubin > 1.5 × ULN at screening
23. Any other laboratory test results that, in the opinion of the Investigator, might place a patient at unacceptable risk f

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

Health Condition(s) or Problem(s) studied

Systemic lupus erythematosus
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: BOS161721
Product Code: BOS161721
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not known
CAS Number: 2229685-51-0
Current Sponsor code: BOS161721
Other descriptive name: IMMUNOGLOBULIN G
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50 -
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): POC Phase 2 Primary (Efficacy) Endpoints:

The proportion of patients with a SRI-4 response at Day 210.

Timepoint(s) of evaluation of this end point: Timepoints for evaluation of POC primary endpoints are listed in the endpoint description above.

Secondary Objective: POC Phase 2 Secondary Objectives:

To demonstrate a superior effect of BOS161721 at the chosen dose compared with placebo for response on clinical indicators of SLE activity, in adult patients with moderately to severely active SLE on limited background standard of care treatment.

Main Objective: Proof of Concept (POC) Phase 2 Primary Objective:

To demonstrate a superior effect of BOS161721 at the chosen dose compared with placebo for response on the SRI-4.

Secondary Outcome(s)

Secondary end point(s): POC Phase 2 Secondary (Efficacy) Endpoints:

• The proportion of patients with:
- SRI-4 response at each visit
- SRI-5 and SRI-6 response at each visit
- a sustained reduction of oral corticosteroid (CS) (= 10 mg/day and = Day 0 dose) between Day 120 and Day 210
- new BILAG A flare or > 1 BILAG B flares relative to baseline through Day 210
- PGA worsening
- a BICLA response
- a CLASI response
- medication failures
• Results and changes from baseline in:
- CLASI
- swollen and tender joints ACR-28
- SLEDAI-2K
- SLICC/ACR damage index
• Time to medication failure
• Duration of longest SRI-4 response
• Time to first SRI-4 response
• Time to BILAG A flare or > 1 BILAG B flare compared to baseline through Day 210

Timepoint(s) of evaluation of this end point: Timepoints for evaluation of POC secondary endpoints are listed in the endpoint description above.

Secondary ID(s)

2018-000305-23-BG

NCT03371251

BOS161721-02

Source(s) of Monetary Support

Boston Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 15/01/2019
Contact: