A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Anti-body Positive Membranous Nephropathy (aMN) - M-PLACE

Phase 2

Withdrawn

• Conditions: anti-PLA2R antibody positive membranous nephropathy; nephropathy; 10029149

• Registration Number: NL-OMON49767
• Lead Sponsor: MorphoSys AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 2

Inclusion Criteria

1. *18 to *80 years (at date of signing ICF)
2. Urine protein to creatinine ratio (UPCR) of * 3.0000 g/g OR proteinuria *
3.500 g/24 h from 24-hr urine at screening
3. Active and anti-PLA2R antibody positive MN in need for IST according to
investigator judgement and with diagnostic biopsy, archival biopsy
acquired within 5 years prior to screening is acceptable
4. Estimated glomerular filtration rate (eGFR) *50 ml/min/1.73m² or >30 and <50
ml/min/1.73m², and IFTA (interstitial fibrosis and tub-ular
atrophy) score of less than 25% on a renal biopsy obtained within the last 6
months prior to start of screening. If a subject falls into the latter
range without availability of an adequate biopsy, a biopsy at screening should
be performed for IFTA assessment.
5. Not in spontaneous remission despite proper treatment with ACEIs, ARBs
(sufficient dose and treatment duration) as per clinical practice
and guidelines. If the PI determines that a subject is intolerant to an ACEI or
ARB, the reason must be documented and approval obtained
from the Medical Monitor prior to enrolment.
6. Systolic BP * 150 mmHg and diastolic BP * 100 mmHg after a period of 5
minutes of rest as measured at screening
7. Subject vaccinated against Pneumococcus within the last 5 years prior to
date of signing ICF (subjects may be vaccinated during screening to meet this
criterion; interval to first dose of MOR202 must be at least 14days (1)).
8. Cohort 1 comprises newly or relapsed subjects: Serum anti-PLA2R antibodies
*50.0 RU/ml determined by Euroimmun ELISA at central
laboratory.
9. Cohort 2 comprises therapy refractory subjects:
a. subject did not achieve immunological remission after prior IST(s) as
documented by the investigator AND
b. subject is without promising standard therapeutic options as documented by
the investigator(i.e. investigator expects efficacy or safety issues with
remaining IST options AND
c. serum anti-PLA2R antibodies *20RU/mL measured at screening by the Euroimmun
ELISA at central laboratory
10. Female of non-childbearing potential fulfilling one of the criteria:
a. post-menopausal: after 12 months of natural (spontaneous)
amenorrhea with an appropriate clinical profile (e.g. age appropriate, history
of vasomotor symptoms)
b. surgically sterile: tubal ligation at least 6 weeks before taking trial
treatment, hysterectomy, or bilateral oophorectomy
c. genetically sterile: e. g. Turner syndrome, uterine agenesis.
11. Sexually active females of reproductive potential should use one of the
following contraception options until 3 months after the last dose of
MOR202:
a. One method of contraception that has a typical use failure rate of <1%
(i.e., less than 1 pregnancy expected per 100 women), which would include
sterilization surgery for women, sterilization implant for women, sterilization
surgery for men, Copper IUD, IUD with progestin, or implantable rod
b. A hormonal method of contraception (i.e., shot/injection, oral
contraceptive, contraceptive patch, vaginal contraceptive ring, having
typical use failure rate * 9%) plus a barrier method (i.e., diaphragm with
spermicide, sponge with spermicide, cervical cap with spermicide,
male condom, female condom, spermicide alone).
Note: France will only enroll patients in Cohort 2.

Exclusion Criteria

1. Hemoglobin < 80 g/L
2. Thrombocytopenia: Platelets < 100.0x10^9/L
3. Neutropenia: Neutrophils < 1.5x10^9/L
4. Leukopenia: Leukocytes < 3.0x10^9/L
5. Hypogammaglobulinemia: Serum immunoglobulins *4.0 g/L
6. B-cells < 5 x 106/L
7. Secondary cause of MN (e.g. SLE, medications, malignancies) as determined by
the investigator
8. Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus
nephritis, IgA nephropathy)
9. Diabetes mellitus type 1
10. Diabetes mellitus type 2: Subjects with type 2 diabetes mellitus may only
enter the clinical trial if a kidney biopsy performed within 6 months
prior to screening shows membranous nephropathy without histological signs of
diabetic nephropathy and their disease is controlled, such as:
o Hba1c <8.0 % or 64 mmol/mol,
o No diabetic retinopathy known
o No peripheral neuropathy known
11. Previous treatment with an anti-CD38 antibody
12. Subject received treatment with:
a.Mycophenolate mofetil (MMF) or high dose corticosteroids (> 20 mg
prednisone/day), within 30 days prior to screening OR
b.Alkylating agents (e.g. cyclophosphamide [CYC]) or CNIs (e.g. tacrolimus,
cyclosporine A [CSA]) within 90 days OR
c.Biologic drugs including RTX within 180 days
d.Any other oral/parenteral IST within 180 days.
13. Significant uncontrolled cardiovascular disease or cardiac insufficiency
(New York Heart Association [NYHA] class IV) as judged by the investigator
14. Clinically relevant findings on a 12 lead ECG as determined by the
investigator at screening
15. History of significant cerebrovascular disease or sensory or motor
neuropathy of tox-icity * grade 3
16. Total bilirubin, aspartate aminotransferase and alanine aminotransferase
>1.5 x ULN, alkaline phosphatase >2.0 x ULN
17. Treatment within five terminal half-lives (if known) or within the last 30
days prior to baseline (whatever is longer) with investigational drugs.
18. Known or suspected hypersensitivity to MOR202 and its excipients
(L-histidine, su-crose, polysorbate 20)
19. Serologic or virologic markers positive for HIV, hepatitis C (subjects with
positive anti hepatitis C virus [anti-HCV] antibody but negative HCV
RNA polymerase chain reaction [PCR] may enroll) or active or latent hepatitis B
(subjects with positive hepatitis B surface antigen [HBsAg]
are excluded, subjects with isolated positive hepatitis B core antibody
[anti-HBc] but non-detectable hepatitis B virus (HBV) DNA by PCR may
be enrolled).
20. For any other preexisting symptoms and impairments of health classified or
any re-sidual toxicity from prior therapy * grade 3 (NCICTCAE,
see 3.2): these subjects may be included upon confirmation by the medical
department of the sponsor
21. Pregnancy or breast feeding
22.Any active infection (viral, fungal, bacterial) requiring systemic therapy.
23.Any malignancy within 5 years prior to date of screening, with the exception
of adequately treated in situ carcinoma of the cervix, uteri,
basal or squamous cell carcinoma or non-melanomatous skin cancer.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>PRIMARY ENDPOINT:<br /><br>Incidence and severity of treatment-emergent adverse events (TEAE)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>KEY SECONDARY ENDPOINT:<br /><br>Best Immunological Response: rate of sICR, ICR and IPR based on re-duction of<br /><br>serum anti-PLA2R antibody titer<br /><br>SECONDARY ENDPOINTS:<br /><br>1. Number and antibody titers of subjects tested positive for anti-MOR202<br /><br>antibodies<br /><br>2. MOR202 serum concentrations after multiple i.v. administra-tions<br /><br>3. Incidence and severity of adverse drug reactions (ADRs) in the follow-up<br /><br>phase.</p><br>