A two part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-a Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren’s Syndrome.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2016-004258-14-GB
• Date of registration: 21/12/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A two part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-a Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren’s Syndrome.
• Scientific title: A two part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-a Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren’s Syndrome. - GSK2618960, PH2a, 2-part, repeat IV dose, Immunogenecity, Safety and PK/PD Study in pSS pts
• Date of first enrolment: 21/02/2017
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004258-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Part II- Double blind; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria (Part I)
A participant will be eligible for inclusion in this study only if all of the following criteria
apply:
AGE
1. Between 18 and 70 years of age at the time of signing the informed consent.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Diagnosis of primary Sjögren’s Syndrome according to the American-European
Consensus Group criteria (Vitali, 2002).
3. Documented previous biopsy evidence of salivary gland inflammation consistent with pSS and/or documented history of anti-Ro (SSA) and/or anti-La (SSB) antibodies.
SEX
4. Male and female participants
Male participants
Males with FRP partners must agree to utilize two forms of complementary contraception consisting of one barrier method (male condom or female
diaphragm) and one method from one of the options listed in the Modified List
of Highly Effective Methods for Avoiding Pregnancy in FRP (see Appendix 5) from start of screening until 6 months after termination of MTX administration.
Female participants, where one of the following conditions apply:
a. Non reproductive potential as defined as:
i. pre-menopausal females with one of the following:
-documented tubal ligation
-documented hysteroscopic tubal occlusion
-procedure with followup confirmation of bilateral tubal occlusion
-hysterectomy
-documented bilateral oophorectomy
ii. post-menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating
hormone (FSH) > 40 million international unit (MIU)/mL and oestradiol < 40 picogram (pg)/mL (< 140 picomol (pmol)/L) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal
status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation
of their postmenopausal status, they can resume use of HRT during the study.
b. Reproductive potential with:
- negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening, AND a negative urine pregnancy test on the first day of MTX run-in phase prior to administration, AND during MTX run in phase as per routine monitoring in the MTX label AND negative urine pregnancy test on Day 1 prior to administration of GSK2618960 (or placebo).
- agrees to utilize two forms of complementary contraception consisting of one barrier method (male condom or female diaphragm) and one method from one of the options listed in the Modified List of Highly
Effective Methods for Avoiding Pregnancy in FRP (see Appendix 5) from start of screening until 6 months after termination of MTX administration.
Those participants that were on MTX therapy prior to enrolling into the study, and that were using consistently one contraception method from the list of
Exclusion criteria:
Exclusion Criteria (Part I)
A participant will not be eligible for inclusion in this study if any of the following criteria
apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL)
1. Diagnosis of Sjögren’s syndrome (SS) associated with other immune-mediated disorders, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, IgG4 or Graft versus Host disease.
2. Any history of the following systemic manifestations of primary Sjögren’s syndrome: vasculitis, central nervous system (CNS).
3. Contraindications to MTX according to SPC.
4. Any history of acute renal failure, tubulointerstitial nephritis, glomerulonephritis or presence of chronic kidney disease.
Patients with history of distal tubular acidosis are allowed, provided the patients are asymptomatic at the time of screening, MTX run-in period and baseline.
5. Any history of lymphoma or fixed unilateral or bilateral parotid gland swelling suggestive of lymphoma.
6. Monoclonal gammopathy as defined by: IgA or IgM monoclonal gammopathy, or abnormal Free Light Chain ratio, or serum M-protein>20 g/L.
7. Previous major organ transplant or haematopoietic stem cell transplantation.
8. Previous head or neck irradiation.
9. Leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence
of metastatic disease for 3 years
10. Breast cancer within the past 10 years.
11. Positive serology for:
-HIV
-Hepatitis C (HCV) or presence of HCV ribonucleic acid (RNA)
-Hepatitis B (HB), defined as HB surface antigen positive (HBsAg+) OR HB core antibody positive (HBcAb+)
12. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration <5 mm at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
Note: The choice to perform a TST or a QuantiFERON-TB Gold test will be made by the investigator according to local licensing and standard of care. The QuantiFERON-TB
Gold test can only be used in countries where it is licensed, and the use of this test is dependent on previous treatment(s). This test may not be suitable if previous treatment(s) produced significant immunosupression.
13. Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows:
a. Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes
zoster and atypical mycobacteria). OR
b. Discharged from hospitalization for treatment of infection within 30 days of screening.
OR
c. Use of parenteral (IV or intramuscular [IM])antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) wit

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

Health Condition(s) or Problem(s) studied

Primary Sjögren’s Syndrome
MedDRA version: 19.0 Level: LLT Classification code 10021295 Term: IL-7 therapy System Organ Class: 100000004865

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

Intervention(s)

Product Name: GSK2618960
Product Code: GSK2618960
Pharmaceutical Form: Solution for injection
INN or Proposed INN: GSK2618960
CAS Number: N/A
Current Sponsor code: GSK2618960
Other descriptive name: GSK2618960
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Part I
-Characterise the pharmacokinetics (PK) of GSK2618960 following repeat IV administration.
-Assess immunogenicity of GSK2618960.

Part II
-Characterise the PK of GSK2618960
following repeat IV administration over
12 weeks.
-Assess immunogenicity of GSK2618960.
-Characterise pharmacodynamics following repeat IV administration of GSK2618960
-Effect of repeat administration of GSK2618960 on disease markers in salivary gland tissue.

Timepoint(s) of evaluation of this end point: Safety data will be reviewed frequently during study and overall analysis at end of study

Main Objective: Part I
Assess safety and tolerability of repeat intravenous (IV) administration of GSK2618960.

Part II
Assess safety and tolerability of repeat IV administration of GSK2618960

Primary end point(s): Same primary endpoints for Part 1 and 2: Adverse Events (AEs), Clinical laboratory values (Haematology; Clinical Chemistry, Urinalysis), Vital Signs, Electrocardiogram (ECG)

Secondary Outcome(s)

Secondary end point(s): Part 1:
1)
-GSK2618960 Plasma concentrations
-GSK2618960 PK parameters, including, but not limited to, maximum concentration (Cmax), minimum concentration (Cmin), Area Under the Curve (AUC) during dosing intervals, where appropriate,
2)
-Incidence, titres and time to onset of anti drug antibodies (ADA)
-Incidence of neutralising ADA (binding at the complementarity determining regions (CDRs))

Part 2:
1)
-GSK2618960 Plasma concentrations
-GSK2618960 Plasma PK parameters, including, but not limited to, Cmax, Cmin, AUC during dosing intervals, where appropriate; 2)
-Incidence, titres and time to onset of ADA
-Incidence of neutralising ADA (binding at the CDRs);

3)
-RO on circulating T cells over time
-Percentage inhibition of STAT5 phosphorylation in T cells over time;
4) Change from baseline in Focus Score

Timepoint(s) of evaluation of this end point: All data will be reviewed frequently during study for safety and overall analysis at end of study

Secondary ID(s)

201579

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 30/12/2018
• Date Completed: 19/09/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004258-14/results