Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2015-002345-64-CZ
• Date of registration: 08/09/2015
• Prospective Registration: Yes
• Primary sponsor: Baxalta Innovations GmbH
• Public title: Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy
• Scientific title: A Phase 2 Study to Assess the Efficacy and Safety of Intravenous Infusion with Human Soluble Recombinant Fc-gamma Receptor IIB (SM101/BAX 1810) in Subjects with Immunoglobulin A Nephropathy (IgAN) - Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy
• Date of first enrolment: 12/11/2015
• Target sample size: 51
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002345-64
• 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: 3

Countries of recruitment

Belgium, Canada, Czech Republic, Denmark, Germany, Hong Kong, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Development
• Affiliation: Baxalta Innovation GmbH

• Name: Clinical Development
• Affiliation: Baxalta Innovation GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is 18 years of age or older at the time of Screening.
2. Subject may be of either gender and of any race or ethnicity.
3. Subject must have a biopsy-proven diagnosis of IgAN (obtained within 8 years
prior to Screening).
4. Subject’s blood pressure is =130/80 mmHg at Screening.
5. Subject is on maximally tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) for at least 3 month prior to Baseline visit.
6. Subject must present at Screening with current proteinuria levels between 1 g/24 h and 3.5 g/24 h.
7. Subject must present at Screening with eGFR [CKD-EPI] >40 mL/min/1.73m2.
8. If a female of childbearing potential, subject must have a negative pregnancy test at Screening, is not currently breastfeeding, and agrees to employ adequate birth control measures for the duration of the study. Male subjects with female partners of childbearing potential must agree to use adequate birth control measures for the duration of the study.
9. Subject is willing and able to comply with the requirements of this protocol and
agrees to sign an informed consent form prior to any study-related activities.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 46
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Subject has a history or current evidence of renal disease other than IgAN
2. Subjects with evidence of rapidly progressive disease (defined as a decline in
eGFR of =5 mL/min/1.73m2 in the preceding 6 months prior to Baseline)
3. Subject has IgAN with histologic evidence of advanced tubular atrophy and
interstitial fibrosis (eg, Oxford T2)
4. History or current evidence of other autoimmune disease (eg, SLE, inflammatory
bowel disease, rheumatoid arthritis)
5. History or current evidence of any chronic or uncontrolled medical condition (eg,
diabetes, severe hepatic or cardiovascular disease, alcohol or drug addiction)
which could, in the opinion of the Investigator, affect the subject’s safety and
ability to adhere to this protocol, or otherwise confound the results of the study
6. History or current evidence of a severe acute (ie, within 4 weeks prior to
Baseline) or chronic infection (eg, HIV, hepatitis B or C, tuberculosis, systemic
fungal infection [active or latent])
7. Use of systemic corticosteroids within 3 months prior to Baseline, or anticipated
use during the treatment period (Week 1 through Week 4). Note: Corticosteroids
administered by inhalation or intranasally, or limited topical use of low-potency
topical corticosteroids (ie, Class 6 and 7) are allowed throughout the study.
8. Known hypersensitivity or allergic reaction to any E. coli-derived recombinant
product, or to the IP or any of its excipients
9. Treatment with any immunomodulatory/immunosuppressive compound or
monoclonal antibody for any indication within 6 months (unless otherwise
stated) prior to Screening (eg, B cell-depleting agents [eg, rituximab,
epratuzumab] for =48 weeks; B-cell modifying agents [eg, belimumab, atacicept]
for =24 weeks; IV immunoglobulins for =12 weeks and all other
immunosuppressive treatments [eg, methotrexate, cyclophosphamide,
cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine] for =12 weeks)
10. Clinically significant laboratory abnormalities prior to Baseline (eg, absolute
neutrophil count <1000 cells/µL; platelet count <100,000/µL; hemoglobin =10
g/dL; aspartate aminotransferase [AST], and alanine aminotransferase [ALT] =3
times the upper limit of normal)
11. History of any malignancy within past 5 years prior to Screening (except for
basal and squamous cell carcinomas of the skin, in situ cervical cancer, and
stable prostate cancer that does not require treatment)
12. History of tonsillectomy within 2 months prior to Screening
13. Subject has participated in another clinical study involving an IP or
investigational device within 30 days prior to Screening or is scheduled to
participate in another clinical study involving an IP or investigational device
during the course of this study
14. Subject is a family member or employee of the Investigator
15. A female subject who is pregnant or nursing at the time of Screening


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

Health Condition(s) or Problem(s) studied

IgA Nephropathy
MedDRA version: 18.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Code: SM101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not available
Current Sponsor code: SM101
Other descriptive name: human soluble recombinant Fc-gamma receptor IIB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To assess the efficacy of a single treatment cycle of SM101 on the mean percent change in proteinuria from Baseline to Week 24 in subjects with IgAN

Primary end point(s): To assess the efficacy of a single treatment cycle of SM101 on the mean percent change in proteinuria from Baseline to Week 24 in subjects with IgAN
1. Pooled high-dose SM101 and low-dose SM101 versus placebo
2. High-dose SM101 versus placebo
3. Low- dose SM101 versus placebo

Secondary Objective: 1. To assess the safety and tolerability of SM101 in subjects with IgAN
2. To compare the relative efficacy and safety of 12 mg/kg and 24 mg/kg doses of SM101 in the treatment of IgAN
3. To assess the effect of SM101 on renal function, as determined by estimated glomerular filtration rate (eGFR)
4. To compare the effect of treatment with SM101 on the level of IgAN-specific biomarkers
5. To assess the pharmacokinetics (PK) of SM101 in subjects with IgAN

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Secondary end point(s): 1. Pooled high-dose SM101 and low-dose SM101 versus placebo (testing via 2x2
table by pooling high- and low-dose SM101 into single column, using placebo
as the second column).
2. High-dose SM101 versus placebo (testing via 2x2 table, using only SM101
high-dose and placebo)
3. Low- dose SM101 versus placebo (testing via 2x2 table, using only SM101
low-dose and placebo)

Secondary ID(s)

181501

Source(s) of Monetary Support

Baxalta Innovations GmbH