Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 21 February 2022
• Main ID: NCT02605525
• Date of registration: 12/11/2015
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• 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)
• Date of first enrolment: December 31, 2015
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02605525
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 18 years of age or older at the time of screening

2. Participant may be of any race or ethnicity

3. Participant must have a biopsy-proven diagnosis of IgAN.

4. Participant's blood pressure is =130/80 mmHg at Screening

5. Participant is on maximally tolerated dose of an angiotensin-converting enzyme (ACE)
inhibitor and/or angiotensin receptor blocker (ARB) for at least 3 months prior to the
baseline visit.

6. Participant must present at screening with current proteinuria levels between 1 g/24 h
and 3.5 g/24 h, based on spot urine protein-to-creatinine ratio (UPCR)

7. Participant must present at screening with an estimated glomerular filtration rate
(eGFR) >40mL/min/1.73m^2

8. If a female of childbearing potential, participant 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 participants with female partners
of childbearing potential must agree to use adequate birth control measures for the
duration of the study

9. Participant 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

Exclusion Criteria:

1. Participant has a history or current evidence of renal disease other than IgAN

2. Participants with evidence of rapidly progressive disease

3. Participant has IgAN with histologic evidence of advanced tubular atrophy and
interstitial

4. History or current evidence of other autoimmune disease

5. History or current evidence of any chronic or uncontrolled medical condition which
could, in the opinion of the Investigator, affect the participant's safety and ability
to adhere to this protocol

6. History or current evidence of a severe acute or chronic infection

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 are allowed throughout the study.

8. Known hypersensitivity or allergic reaction to any E. coli-derived recombinant
product, yeast extract, 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

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. Participation 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. Participant is a family member or employee of the Investigator

15. A female participant who is pregnant or nursing at the time of screening



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Immunoglobulin A Nephropathy

Intervention(s)

Other: Placebo

Biological: SM101

Primary Outcome(s)

Percent change in proteinuria from Baseline to Week 24 [Time Frame: Baseline and Week 24]

Secondary Outcome(s)

Number of participants who experience any treatment-related serious adverse event (SAE) or severe adverse events (AE) during the course of the treatment period or subsequent follow-up period [Time Frame: Throughout the study period of approximately 19 months]

Number of participants who experience temporally-related adverse events (AEs) [Time Frame: Baseline through 72 hours of IP administration]

Pharmacokinetics: maximum observed concentration (Cmax) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Pharmacokinetics: systemic clearance (CL) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Pharmacokinetics: time of maximum observed concentration (Cmax) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Pharmacokinetics: volume of distribution at steady state (Vss) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Number of infusions that had to be slowed, interrupted, or terminated due to adverse events (AEs) or serious adverse events (SAEs) [Time Frame: Throughout the study period of approximately 19 months]

Number of participants with any clinically significant change in vital signs during investigational product (IP) administration or within 30 minutes following administration [Time Frame: Baseline through 30 minutes following IP administration]

Mean change from Baseline in Estimated glomerular filtration rate (eGFR) [Time Frame: Baseline, Week 8, Week 12, Week 18, and Week 24]

Number of infusions associated with adverse events (AEs) or serious adverse events (SAEs) , regardless of causality [Time Frame: Throughout the study period of approximately 19 months]

Number of participants who demonstrate a =30% reduction from Baseline in proteinuria [Time Frame: Baseline, Week 8, Week 12, Week 18, and Week 24]

Clinically significant abnormal laboratory assessments [Time Frame: Throughout the study period of approximately 19 months]

Number of participants who experience serious adverse events (SAEs) or adverse events (AEs) [Time Frame: Throughout the study period of approximately 19 months]

Number of participants who reach and maintain proteinuria levels below 1.0 g/24 h [Time Frame: Week 8, Week 12, Week 18, and Week 24]

Number of participants with detectable levels of antidrug antibodies (ADAs) [Time Frame: Baseline, Week 3, Week 4, Week 12, Week 24, or early termination from the study]

Pharmacokinetics: area under the concentration-time curve during a dosing interval (AUC(0-tau)) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Pharmacokinetics: terminal half-life (t1/2) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Pharmacokinetics: volume of distribution at the terminal phase (Vz) [Time Frame: Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.]

Secondary ID(s)

181501

2015-002345-64

Source(s) of Monetary Support

Please refer to primary and secondary sponsors