Clinical trial NCT03945318: Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN)
Official title: A Phase 1/2, Multicenter Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: IgA Nephropathy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-05-10
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 (SAD-HV) is a randomized, placebo-controlled single ascending dose design in HVs. Part 2 (MAD-HV): is a randomized, placebo-controlled multiple ascending dose design in HVs. Part 3 (MD-IgAN) is an open-label multiple dose design in participants with IgAN. Part 4 (IgAN) is open-label retreatment for Part 3 participants.
Primary purpose: TREATMENT

Brief summary: Multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BION-1301 in healthy volunteers and adults with IgA Nephropathy (IgAN).

Detailed description: This is a Phase 1/2 study of BION-1301, a first-in-class humanized IgG4 anti-a proliferation-inducing ligand (APRIL) monoclonal antibody.

The study will be conducted in three parts. Part 1: double-blind, randomized, placebo-controlled, single ascending dose (SAD) in healthy volunteers (HVs). Part 2: double-blind, randomized, placebo-controlled multiple ascending dose (MAD) in HVs. Part 3: Open-label, multiple dose (MD) in participants with IgAN. Part 4: Retreatment period

Parts 1 and 2 have been completed. Part 3 enrollment is complete. Part 4 enrollment is open for eligible participants from Part 3.

The study will enroll up to 40 participants with IgAN.

Eligibility criteria: Inclusion Criteria for Healthy Volunteers:

1. Healthy male or female volunteers, 18 to 55 years old
2. Females must be of non-childbearing potential
3. Males must agree to follow the protocol-specified contraception guidance
4. Body mass index (BMI) between 18 and 35 kg/m\^2, with a weight of at least 50 kg
5. Non-smoker, defined as an individual who has not smoked previously and/or who has discontinued smoking or the use of nicotine/nicotine-containing products at least 3 months before Screening
6. Able to provide signed informed consent

Exclusion Criteria for Healthy Volunteers:

1. Regular consumption of alcohol within 6 months prior to Screening, or use of soft drugs (such as marijuana) within 3 months prior to Screening, or hard drugs (such as cocaine and phencyclidine) within 1 year prior to Screening and/or positive blood or urine test results for drugs of abuse or alcohol at Screening or Admission
2. Donated blood in the 3 months prior to the first dose of study drug, plasma in the 7 days prior to the first dose of study drug, or platelets in the 6 weeks prior to the first dose of study drug
3. History or evidence of a clinically significant disorder, condition, or disease that could pose a risk to subject safety or interfere with the study, or would make the subject unsuitable for participation, eg, respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, or psychiatric disease
4. Female who is breastfeeding or who has a positive serum pregnancy test at Screening or a positive urine pregnancy test on Day -1

Inclusion Criteria for Adults with IgAN:

1. Male or female ≥18 years old at Screening
2. Women of child-bearing potential (WOCBP; per CTFG 2014) must agree to follow the protocol-specified contraception guidance throughout the study (from Screening through approximately 6 months after the final dose of study drug)
3. Males must agree to follow the protocol-specified contraception guidance throughout the study (from Screening through approximately 6 months after the final dose of study drug)
4. BMI between 18 and 40 kg/m\^2, inclusive, at Screening with a weight of at least 50 kg
5. Diagnosis of IgAN verified by biopsy taken within the past 10 years
6. Urine protein ≥ 0.5 g/24h; OR UPCR ≥ 0.5 g/g (or ≥ 50 mg/mmol)
7. eGFR (per Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) or measured GFR ≥ 30 mL/min per 1.73 m\^2
8. Stable on an optimized dose of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin-receptor blockers (ARBs) for at least 3 months prior to Screening or intolerant to ACE/ARB

Exclusion Criteria for Adults with IgAN:

1. Known or suspected allergy or hypersensitivity to any component of BION-1301, or history of severe hypersensitivity reaction to any monoclonal antibody
2. Donated blood in the 3 months prior to the first dose of study drug; plasma in the 7 days prior to the first dose of study drug; or platelets in the 6 weeks prior to the first dose of study drug
3. Participated in any other study in which receipt of an investigational new drug, or investigational device occurred within 28 days, or 5 half-lives (whichever is longer) of first dose of study drug in the present study
4. Secondary forms of IgAN as defined by the treating physician (eg, Henoch-Schönlein purpura patients and those with associated alcoholic cirrhosis)
5. Received systemic corticosteroid therapy (\> 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 3 months prior to the first dose of study drug

PART 4 Eligibility Criteria for Re-treatment Due to Evidence of Disease Progression

(Option 1) Inclusion Criteria for Re-treatment Due to Evidence of Disease Progression

1. Completed Part 3 of the study through Week 124 and entered the 52-week follow-up period.
2. UPCR ≥ 0.5 g/g AND ≥ 30% increase from EOT (Week 124). Both proteinuria criteria must be met by a 24-hour urine assessment during the 52-week follow-up period. In addition to the scheduled assessments, investigators may order periodic FMV assessments (for example monthly) to follow a patient more closely. Based on an off-schedule FMV result, or other laboratory or clinical evidence, investigators may order an off-schedule 24-urine collection to confirm disease progression.

Exclusion Criteria for Re-treatment Due to Evidence of Disease Progression

1. Based on the Investigator's judgment, the patient would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual patient which outweighs the expected benefit from resuming treatment.
2. Received systemic corticosteroid therapy, including budesonide, for \>14 days within 3 months prior to the first dose of Part 4 for the treatment of IgAN
3. Received any other form of immunosuppressive therapy such as, but not limited to mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, etc) within 3 months prior to the first dose of Part 4 study drug
4. Received investigational products for the treatment of IgAN, other than BIO-1301
5. Received newly approved immunosuppressive or immunomodulatory therapy for the treatment of IgAN including but not limited to other anti-APRIL therapies and iptacopan

Eligibility Criteria for Optional Re-treatment (Option 2)

Inclusion Criteria for Optional Re-treatment

1. Completed Part 3 of the study through Week 124 and completed of the 52-week follow-up period.

Exclusion Criteria for Optional Re-treatment

1. Based on the Investigator's judgment, the patient would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual patient which outweighs the expected benefit from resuming treatment.
2. Received systemic corticosteroid therapy, including budesonide, for \>14 days within 3 months prior to the first dose in Part 4 for the treatment of IgAN
3. Received any other form of immunosuppressive therapy (such as, but not limited to mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, etc) within 3 months prior to the first dose of Part 4 study drug
4. Received investigational products for the treatment of IgAN, other than BIO-1301
5. Received newly approved immunosuppressive or immunomodulatory therapy for the treatment of IgAN including but not limited to other anti-APRIL therapies and iptacopan

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events (TEAEs) as assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Participants followed from date of enrollment until the end of study, assessed up to 76 weeks.
measure: Severity of TEAEs as assessed according to NCI-CTCAE
timeFrame: Participants followed from date of enrollment until the end of study, assessed up to 76 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Denver
country: United States
facility: Colorado Kidney Care, P.C.
state: Colorado
city: Orlando
country: United States
facility: Nephrology Associates of Central Florida
state: Florida
city: Tampa
country: United States
facility: Elixia Tampa, LLC
state: Florida
city: Clifton Park
country: United States
facility: New York Nephrology
state: New York
city: Oklahoma City
country: United States
facility: Chris Sholer, P.C.
state: Oklahoma
city: Arlington
country: United States
facility: Liberty Research Center
state: Texas
city: Dallas
country: United States
facility: Liberty Research Center
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Cheonan
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Cheonan
state: Chungcheongnamdo
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Goyang-Si
country: Korea, Republic of
facility: National Health Insurance Service Ilsan Hospital
state: Gyeonggi-Do
city: Guri-si
country: Korea, Republic of
facility: Hanyang University Guri Hostpital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: PAREXEL Early Phase Clinical Unit
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: