A Multicenter Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Zigakibart in Adults With Primary IgA Nephropathy.

The purpose of this study is to determine if zigakibart is safe and effective for long-term use in patients with immunoglobulin A nephropathy (IgAN). This is an extension study for patients who have already completed an another zigakibart study.

CT.gov Identifier

NCT06858319

EudraCT Identifier

N/A

CTIS:

2024-519638-22-00

Collaborator

N/A

Study Contact Information

+41 61 324 0000

Recruiting

Study Details

Diseases

IgA nephropathy

Study Drug

Zigakibart

Genes

N/A

Study Dates

Jul 2025 - Jun 2031

Sex

Female & Male

Age

18 - 100 Years

Inclusion and Exclusion Criteria

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the OLE study.
2. Completion of the parent study (both participants assigned to receive the investigational product and placebo) as defined by the respective protocol.
3. Per Investigator's clinical judgment, the participant may benefit from receiving open-label treatment of zigakibart 600 mg s.c. Q2W. Informed consent must be signed before participating in an OLE study.
The preliminary studies (including participants assigned to receive the investigational drug and placebo) have been completed in accordance with their respective protocols.
Based on the researchers' clinical judgment, participants may benefit from open-label treatment with zigakibart 600 mg subcutaneously every two weeks.

Exclusion Criteria:

1. Participants who prematurely withdrew from zigakibart parent studies in IgAN for any reason.
2. Participants who at the time of first study treatment administration in the OLE are receiving chronic dialysis (≥30 days) or who require kidney transplantation.
3. Acute kidney injury (AKI), defined by AKIN criteria (Mehta et al 2007) within 4 weeks of first study treatment administration in the OLE study.
4. Clinical suspicion or diagnosis of rapidly progressive glomerulonephritis (RPGN), defined by KDIGO guidelines, or another glomerulopathy at the time of first study treatment administration in the OLE study.
5. Received a live vaccination within 12 weeks prior to first study treatment administration in the OLE study or plan to have a live vaccination within 6 months after the last dose of study treatment.
6. Use of systemic corticosteroid therapy (including budesonide) or other immunosuppressive therapy such as but not limited to mycophenolate, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, etc., and herbs such as Tripterygium Wilfordii Hook F, Caulis sinomenii, and Sinomenium acutum for > 2 weeks in the 12 weeks prior to first study treatment administration in the OLE study; use of rituximab within 180-days of first study treatment administration in the OLE study.
7. Current severe infection at the time of first study treatment in the OLE study or history of recurrent, severe, infections as determined by the Investigator.
8. Newly diagnosed positive serology for hepatitis A virus IgM antibodies (anti-HAV IgM), hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibodies (participants who completed treatment and are persistently antibody positive but have documentation of negative HCV polymerase chain reaction [PCR] will be allowed), or antibodies to HIV-1 and/or HIV-2.
9. Newly diagnosed malignancy (participants with basal cell carcinoma that was completely resected or curatively treated cervical carcinoma in situ or low-risk prostate cancer (i.e., Gleason score < 7 and prostate specific antigen < 10 ng/mL) are eligible for the study).
10. Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose.
11. History or evidence of any other clinically significant medical or psychiatric disorder, condition, disease, or laboratory finding that, in the discretion of the Investigator, constitutes an uncertain or unfavorable benefit-risk for continued long-term therapy with zigakibart.
12. Confirmed IgG levels < 3 g/L prior to first study treatment administration in the OLE study.
13. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, from menarche until becoming post-menopausal unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 24 weeks after stopping study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).
14. Sexually active males unwilling to use a highly effective methods of contraception during intercourse while taking study treatment and for 24 weeks after stopping study treatment. In addition, male participants must not donate sperm for the time period specified above.
Highly effective contraception methods for both women and men include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
* Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment are they considered to be not of childbearing potential.
* Bilateral tubal occlusion, bilateral tubal ligation (at least six weeks before taking study treatment).
* Sterilization (vasectomy) of male partner(s) of the female participant at least 6 months prior to first study treatment provided partner(s) has(have) received medical confirmation of surgical success.
* Use of hormonal contraception methods:
* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal.
* Progestogen-only hormonal contraception (where inhibition of ovulation is not the primary or only mode of action): oral, injectable or implantable.
* Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). In case of use of hormonal contraception, women should have been stable on the same method for a minimum of 3 months before taking study treatment. Participants who withdraw early from the zigakibart IgAN preliminary study for any reason.
Participants who were undergoing long-term dialysis (≥30 days) or required a kidney transplant at the time of the first study drug administration in the OLE study.
This study is the first to investigate acute kidney injury (AKI) within 4 weeks prior to drug administration (as defined by the AKIN criteria) in the OLE study.
When the drug was first administered in the OLE study, patients were clinically suspected or diagnosed with rapidly progressive glomerulonephritis (RPGN) or other glomerular diseases as defined by the KDIGO guidelines.
Those who received a live vaccine within 12 weeks prior to the first administration of the study drug in the OLE study, or who plan to receive a live vaccine within 6 months after the last administration of the study drug.
The patient received systemic corticosteroid therapy (including budesonide) or other immunosuppressive therapy, including but not limited to mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, and herbal remedies such as tripterygium wilfordii wilfordii, tacrolimus acutum, and Sedum aizoon, for more than 2 weeks prior to the first administration of the investigational drug in the OLE study; or received rituximab within 180 days prior to the first administration of the investigational drug in the OLE study.
Active severe infection at the time of first administration in the OLE study, or a history of recurrent severe infection as determined by the investigator.
Newly diagnosed hepatitis A virus IgM antibody (anti-HAV IgM), hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibody (participants who have completed treatment and have persistently positive antibodies but negative HCV polymerase chain reaction [PCR] tests will be allowed), or positive HIV-1 and/or HIV-2 antibody serological tests.
Newly diagnosed malignant tumors (participants with completely resected basal cell carcinoma or cured cervical carcinoma in situ or low-risk prostate cancer (i.e., Gleason score < 7 and prostate-specific antigen < 10 ng/mL) are eligible for the study).
Pregnant or breastfeeding women, or those planning to become pregnant or donate sperm during the study period up to 24 weeks after the last dose.
Based on the investigator's judgment, there is a history or evidence of any other clinically significant medical or mental disorder, condition, disease, or laboratory test results, and such history or evidence constitutes an uncertain or undesirable benefit-risk profile for continued long-term treatment with zigakibart.
In the OLE study, the IgG level confirmed before drug administration was < 3 g/L for the first time.
Women of fertility are defined as all women who are physiologically capable of conceiving, from menarche to menopause. This excludes women who consistently use highly effective contraception (with an annual failure rate of <1%) during and for 24 weeks after stopping the study drug. A woman is considered menopausal if she has experienced 12 months of spontaneous amenorrhea and has corresponding clinical features (e.g., hormonal characteristics confirming menopause and/or a history of age-appropriate vasomotor symptoms).
Sexually active men who are unwilling to use highly effective contraception during intercourse during treatment with the study drug and for 24 weeks after discontinuation of the study drug. Furthermore, male participants are not permitted to donate sperm during these periods. Highly effective contraception for both women and men includes: Complete abstinence (consistent with the participant's preferred and habitual lifestyle). It is important to remember that periodic abstinence (such as the calendar method, ovulation method, symptomatic temperature method, post-ovulation rhythm method) and withdrawal methods are not considered effective contraception. Bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral salpingectomy must have been performed at least 6 weeks prior to receiving the study drug. If only oophorectomy was performed, the woman's reproductive status must be confirmed through subsequent hormone level assessments before she can be considered infertile. Bilateral tubal obstruction or bilateral tubal ligation (must be completed at least 6 weeks prior to receiving the study drug). The male partner of a female participant must have undergone sterilization (vasectomy) at least 6 months prior to the first use of the study drug, and must provide medical documentation confirming the success of the procedure. Hormonal contraceptive methods: Combined hormonal contraceptives (containing estrogen and progestin) that suppress ovulation; oral, vaginal, or transdermal. Hormonal contraceptives containing only progestin (where ovulation suppression is not its primary or sole mechanism of action): oral, injectable, or implantable. Intrauterine device (IUD); or intrauterine hormone-releasing system (IUS); If using hormonal contraception, the woman should have been using the same method for at least 3 months prior to receiving the study drug.

Protocol Summary

Study Locations

To view all trial locations, click here

Contact Us About More Information for the Clinical Trial Concierge Service

Natera’s Clinical Trial Concierge Program is comprised of a dedicated team that helps connect providers and patients with appropriate clinical trials. To learn more about a trial offered through this service, please complete the form below.

Fields marked with asterisk (*) are mandatory.