The goal of the global Phase 1/2 clinical trial is to evaluate whether CID-103, a novel anti-CD38 monoclonal antibody, is safe and effective in adults with with active and chronic active renal allograft antibody mediated rejection (ABMR). The main questions the study aims to answer are:• To evaluate the safety and tolerability of CID-103 in subjects with ABMR with different increasing doses of CID-103.• To evaluate clinical efficacy of CID-103 at an optimal dose in participants with active and chronic active ABMR following renal allograft transplant. The study will be done in two parts: Part A will test increasing doses of CID-103 to see how safe it is and how well people tolerate it. Researchers will also aim to find a safe dose range. Part B will enroll approximately 40 participants to see how well the medicine works and gather more safety and efficacy information. The goal is to find the optimal dose to use in future studies.CID-103 is given through an intravenous (IV) infusion. During the study, participants may receive treatment for up to 12 months, followed by a post-treatment safety follow-up period to check for ongoing safety and effectiveness. This study is an important step toward developing a new treatment for people living with ABMR. If CID-103 is found to be safe and effective, it could offer a new option for patients who do not respond well to current therapies.

Inclusion Criteria:

1. At least 18 years old at time of signing of ICF.
2. Voluntary, written, informed consent prior to study-specific procedures.
3. Functioning living or deceased donor renal allograft ≥ 180 days post-transplant.
4. eGFR ≥ 25 mL/min/1.73 m2 chronic kidney disease epidemiology collaboration (CKD-EPI 2021, see APPENDIX A).
5. HLA class I and/or II antigen-specific antibodies (preformed and/or dnDSA).
6. Existing diagnosis of active or chronic/active ABMR (± C4d in peritubular capillaries) within the last 180 days according to the Banff 2022 classification as per local pathology read.
7. Must have a renal biopsy within 28 days (preferably within 14 days) of first study drug administration for central pathology review. Results of the central pathology review are not required prior to first study drug administration.
8. Participants who have been diagnosed with pre-existing HLA class I/II DSA at the time of their original renal allograft transplant must have received prior treatment with intravenous immune globulin (IVIG) and plasmapheresis (unless contraindicated).
9. Participants with active ABMR may have received prior treatment with IVIG and plasmapheresis (not required).
10. For participants that have received prior IVIG, subcutaneous immunoglobulin (SCIg), plasmapheresis, complement system inhibitors (e.g., eculizumab), proteasome inhibitors (e.g., bortezomib) or an interleukin-6 inhibitor (e.g. tocilizumab), or an anti-CD20 (e.g., rituximab) a washout period ≥12 weeks is required prior to first study drug administration
11. Standardized immune suppression regimen.
12. Adequate organ function without transfusions, within 14 days of first dose of study drug.
13. Contraception.

Exclusion Criteria:

1. ABO-incompatible transplant.

2. Any of the following on baseline biopsy:

   1. T-cell-mediated rejection classified Banff Grade ≥ 1.
   2. de novo or recurrent severe thrombotic microangiopathy.
   3. polyoma virus nephropathy.
   4. de novo or recurrent glomerulonephritis.

3. Acute rejection treatment within 180 days of dosing.

4. Contraindication to repeat biopsies.

5. Previous treatment with other anti-CD38 monoclonal antibodies.

6. Other immunomodulatory antibodies within ≤ 90 days of dosing.

7. Receiving other concurrent investigational therapies or have received investigational therapies within four weeks of the first dose of study drug or five half-lives (if shorter).

8. Participants unable to modify baseline immune suppression.

9. Active viral, bacterial, or fungal infection precluding intensified immunosuppression.

10. Known latent or active tuberculosis.

11. Known active infection with human immunodeficiency virus (HIV).

12. Known active infection.

13. IgG < 400 mg/dL.

14. Other chronic or acute disease(s) likely to interfere with study endpoint evaluation.

15. Active malignant disease or premalignant condition within two years, precluding intensified immunosuppressive therapy.

16. Administration of a live vaccine ≤ 6 weeks of screening.

17. Participation in interventional component of another clinical trial.

18. History or clinical evidence of any surgical or medical condition which the Investigator judges as likely to interfere with the results of the study or pose an additional risk in participating, particularly any pre-existing condition that would put the participant at additional risk should they experience an IRR.

19. Any unresolved treatment-related AE(s) from prior treatment that have not resolved to Grade 1 or baseline value prior to first dose of study drug.

20. Known hypersensitivity to CID-103 excipients or prior severe hypersensitivity to a monoclonal antibody.

21. Participants who experienced a Grade 3 or 4 AE related to prior administration of monoclonal antibodies, which the Investigator feels may recur and/or put the participant at significant risk, should be excluded.

22. Previous Grade 4 anaphylactic reaction to other therapeutic proteins.

23. Chronic dependence on transfusions or hematopoietic growth factors to maintain acceptable blood counts excluding those participants who require ESAs for documented erythropoietin deficiency. Participants cannot have had a transfusion within the past 14 days prior to first dose of study drug or have had more than 1 transfusion in the past month.

24. Inability to perform study baseline red blood cell (RBC) type and crossmatch, phenotype (and genotype, if applicable) or lack of available baseline data on RBC phenotype (or genotype, if applicable).

25. Unable or not willing to agree to the evaluation of RBC antigens by phenotyping or genotyping.

26. Unable or not willing to comply with the protocol and the visit schedule restrictions and assessments therein.