Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation (The ONE Study )

NCT02244801 | Completed Phase 1 DMC

• 1 other identifier: ONEdarTreg14
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I pilot study will evaluate the safety, and tolerability of darTreg infusion for adult, de novo, living donor renal transplant recipients.

Conditions

Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of biopsy-confirmed acute rejection (BCAR) following renal transplantation.

  Explore the immunomodulatory potential, safety and tolerability of a single infusion of darTregs as adjunct immunosuppressive treatment through the incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks following renal transplantation.

  60 weeks post renal transplantation

Secondary Outcomes (10)

• Time to first acute rejection episode

  60 weeks post renal transplantation

• Severity of acute rejection episodes

  60 weeks post renal transplantation

• Total immunosuppressive burden at 60 weeks post-transplantation

  60 weeks post renal transplantation

• Prevention of chronic graft dysfunction (chronic rejection or IF/TA)

  60 weeks post renal transplantation

• Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection

  60 weeks post renal transplantation

Other Outcomes (3)

• Incidence of malignancies arising directly from darTreg infusion

  60 weeks

• incidence of autoimmune disorders

  60 weeks post transplantation

• A Health-Economics Subproject will evaluate the health-related qualify-of-life of trail patients using patient-reported outcome measures

  60 weeks post transplantation

Study Arms (2)

Cohort 1

OTHER

3 subjects treated with a target dose of 300 million darTreg with the possibility of expanding to 5 patients if safety signals should require additional patients be observed at the 300 million dose. The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.

Drug: darTreg infusion

Cohort 2

OTHER

The second cohort will comprise a minimum of 3 and up to 5 subjects treated at a target dose of 900 million darTreg, depending on how many patients were required to be treated in lower dose group. The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.

Drug: darTreg infusion

Interventions

darTreg infusion DRUG

The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients. sBc production for darTreg manufacturing for the second subject in each cohort may be initiated but the second subject may not undergo leukapheresis until the safety review is complete. Once the last subject in the first cohort reaches week 4 post-infusion, the DSMB will conduct a thorough review of all available data to make a determination about proceeding with additional patients at the lower dose or proceeding to the second dosing cohort. sBc production for darTreg manufacturing for the subsequent subject may be initiated but the patient may not undergo leukapheresis until the DSMB( Data Safety and Monitoring Board ) has approved enrollment of subsequent subjects.

Also known as: darTregs

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible for live kidney donation
• At least 18 years of age
• An ABO blood type compatible with the organ recipient
• Willing and able to provide a blood sample for The ONE Study IM (Immune Monitoring) Subproject
• Willing to provide personal and medical/biological data for the trial analysis
• Eligible to give blood for B cell source prior to organ donation
• Signed and dated written informed consent\*. \*For subjects unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the subject has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the subject.
• In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree to undergo phlebotomy to provide donor B cells for the production of darTreg, to provide a blood sample for the IM Subproject, and permit access to their medical records for the collection of specified demographic and medical/biological data for the trial.
• Organ Recipient eligibility:
• Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor
• At least 18 years of age
• Able to commence the immunosuppressive regimen at the protocol-specified time point
• Willing and able to participate in The ONE Study IM and HEC (Health-Economics Subproject) subprojects
• Adequate venous access to support leukapheresis
• Signed and dated written informed consent\*.

You may not qualify if:

• If a prospective donor fulfills any of the following criteria, they are ineligible for the trial:
• Genetically identical to the prospective organ recipient at the HLA (human leukocyte antigen) loci (0-0-0 mismatch)
• CMV-positive and donating to a CMV-negative recipient
• Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation
• Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel
• Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship).
• Patient has previously received any tissue or organ transplant other than the planned kidney graft
• Known contraindication to the protocol-specified treatments / medications
• Genetically identical to the prospective organ donor at the HLA (human leukocyte antigen) loci (0-0-0 mismatch)
• PRA (panel reactive antibody) grade \> 40% within 6 months prior to enrollment
• Previous treatment with any desensitization procedure (with or without IVIg)
• Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin)
• Evidence of significant local or systemic infection
• HIV-positive, EBV-negative or suffering chronic viral hepatitis
• CMV-negative and receiving a kidney from a CMV-positive donor

Sponsors & Collaborators

• University of California, San Francisco: lead
• Seventh Framework Programme: collaborator

Study Sites (1)

University of California San Francisco - Transplant Department. 513 Parnassus Ave HSE 504

San Francisco, California, 94143, United States

Location

Related Publications (9)

• ICH Harmonised Tripartite Guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 Expert Working Group. Stat Med. 1999 Aug 15;18(15):1905-42. No abstract available.

  PMID: 10532877 BACKGROUND

• Francillon A, Pickering G, Belorgey C. Exploratory clinical trials: implementation modes & guidelines, scope and regulatory framework. Therapie. 2009 May-Jun;64(3):149-59. doi: 10.2515/therapie/2009022. Epub 2009 Aug 13. English, French.

  PMID: 19671427 BACKGROUND

• Morris PJ. Transplantation--a medical miracle of the 20th century. N Engl J Med. 2004 Dec 23;351(26):2678-80. doi: 10.1056/NEJMp048256. No abstract available.

  PMID: 15616201 BACKGROUND

• Sayegh MH, Carpenter CB. Transplantation 50 years later--progress, challenges, and promises. N Engl J Med. 2004 Dec 23;351(26):2761-6. doi: 10.1056/NEJMon043418. No abstract available.

  PMID: 15616214 BACKGROUND

• Gibson T, Medawar PB. The fate of skin homografts in man. J Anat. 1943 Jul;77(Pt 4):299-310.4. No abstract available.

  PMID: 17104936 BACKGROUND

• Medawar PB. The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. J Anat. 1944 Oct;78(Pt 5):176-99. No abstract available.

  PMID: 17104960 BACKGROUND

• Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004 Dec 23;351(26):2715-29. doi: 10.1056/NEJMra033540. No abstract available.

  PMID: 15616206 BACKGROUND

• MERRILL JP, MURRAY JE, HARRISON JH, GUILD WR. Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc. 1956 Jan 28;160(4):277-82. doi: 10.1001/jama.1956.02960390027008. No abstract available.

  PMID: 13278189 RESULT

• Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Boger CA, Scotta C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Ollinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyo J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7.

  PMID: 32446407 DERIVED

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Sang-Mo Kang, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 19, 2014
• Study Start: April 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: August 28, 2018
• Last Updated: October 15, 2018

Record last verified: 2018-10

Locations

US (1)