Open-Label Expanded Access for Ebola-Infected Patients to Receive Human mAb Ansuvimab as Therapeutic or for HR PEP

Hemorrhagic Fever, Ebola Clinical Trial

Official title:

Open-Label, Expanded Access Protocol of a Human Monoclonal Antibody, Ansuvimab (mAb114), Administered as an Investigational Therapeutic to Ebola-Infected Patients or as a High-Risk Ebola Post-Expo

Clinical Trial Details — Status: Available

Administrative data

• NCT number: NCT05067166
• Other study ID #: Ansuvimab EAP-2020-DRC
• Secondary ID: Ansuvimab EAP-DR
• Status: Available

Study information

• Verified date: November 2023
• Source: Ridgeback Biotherapeutics, LP
• Contact: Sabue Mulangu, MD,DTMH,PhD
• Phone: 1 833 846 3789
• Email: EAP-requests[@]ridgebackbio.com
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial Summary

The human monoclonal antibody (mAb), ansuvimab (mAb114), will be provided to Ebola-infected patients as either a treatment or as PEP under expanded access. Ansuvimab is administered at 50 mg/kg as a single intravenous (IV) infusion

Description:

This is an open-label, intermediate size patient population, expanded access protocol (EAP) of the ansuvimab investigational product administered once by IV infusion at a dose of about 50 mg/kg (weight-based dosing). Assessment of safety will include clinical observation and monitoring following administration. Patients will be monitored and assessed daily through discharge for safety and the incidence of serious adverse events (SAEs) and AEs that by clinical judgement are atypical for EVD, and any AEs that occur during product infusions. Blood will be collected for ansuvimab PK assessment, sGP quantification and RT-PCR evaluation of viral load by available assay. A blood sample for Ebolavirus viral load measurement is collected before mAb114 administration and at subsequent study timepoints per the Schedule of Evaluations. Subjects will be followed for up to 3 weeks after the product administration or until discharge from the Ebola Treatment Unit (ETU), whichever is later. Survival status for infected patients and/or EVD disease status for PEP subjects will be recorded as applicable. Ansuvimab will be provided for expanded access in the DRC and can be used in any DRC Ebolavirus (Zaire) outbreak location as authorized by the DRC Ministry of Health and the local Institutional Review Board.

Recruitment information / eligibility

• Status: Available
• Enrollment: 0
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Male or female with laboratory confirmed (based on local standard of care) EBOV infection or with recent high-risk EBOV exposure as determined by a treating Physician or designee.
• Able to provide proof of identity to the satisfaction of the clinical team
• Able and willing to complete the informed consent process personally, or if the patient is unable to do so, then informed consent completed by a legally-authorized representative according to local laws and regulations.

Exclusion Criteria:

• Any medical condition that, in the opinion of the Treating Physician, would place the patient at an unreasonably increased risk through participation in this treatment protocol.

Related Conditions & MeSH terms

• Hemorrhagic Fever, Ebola

Intervention

Drug:
• Ansuvimab
single infusion 50 mg/kg IV

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Institut National de Recherche Biomedical	Beni	North Kivu
Congo, The Democratic Republic of the	Institut National de Recherche Biomédicale	Butembo	North Kivu
Congo, The Democratic Republic of the	Institut National de Recherche Biomedical	Mbandaka	Equateur
Sierra Leone	University of Sierra Leone Teaching Hospital Complex	Freetown

Sponsors (2)

Lead Sponsor	Collaborator
Ridgeback Biotherapeutics, LP	Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

Countries where clinical trial is conducted

Congo, The Democratic Republic of the,  Sierra Leone, 

References & Publications (11)

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Broadhurst MJ, Brooks TJ, Pollock NR. Diagnosis of Ebola Virus Disease: Past, Present, and Future. Clin Microbiol Rev. 2016 Oct;29(4):773-93. doi: 10.1128/CMR.00003-16. — View Citation

Cherif MS, Koonrungsesomboon N, Kasse D, Cisse SD, Diallo SB, Cherif F, Camara F, Kone A, Avenido EF, Diakite M, Diallo MP, Le Gall E, Cisse M, Karbwang J, Hirayama K. Ebola virus disease in children during the 2014-2015 epidemic in Guinea: a nationwide cohort study. Eur J Pediatr. 2017 Jun;176(6):791-796. doi: 10.1007/s00431-017-2914-z. Epub 2017 Apr 25. — View Citation

Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25. — View Citation

Fischer WA 2nd, Vetter P, Bausch DG, Burgess T, Davey RT Jr, Fowler R, Hayden FG, Jahrling PB, Kalil AC, Mayers DL, Mehta AK, Uyeki TM, Jacobs M. Ebola virus disease: an update on post-exposure prophylaxis. Lancet Infect Dis. 2018 Jun;18(6):e183-e192. doi: 10.1016/S1473-3099(17)30677-1. Epub 2017 Nov 15. — View Citation

Gaudinski MR, Coates EE, Novik L, Widge A, Houser KV, Burch E, Holman LA, Gordon IJ, Chen GL, Carter C, Nason M, Sitar S, Yamshchikov G, Berkowitz N, Andrews C, Vazquez S, Laurencot C, Misasi J, Arnold F, Carlton K, Lawlor H, Gall J, Bailer RT, McDermott A, Capparelli E, Koup RA, Mascola JR, Graham BS, Sullivan NJ, Ledgerwood JE; VRC 608 Study team. Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study. Lancet. 2019 Mar 2;393(10174):889-898. doi: 10.1016/S0140-6736(19)30036-4. Epub 2019 Jan 24. Erratum In: Lancet. 2020 May 30;395(10238):1694. — View Citation

Jacobs M, Aarons E, Bhagani S, Buchanan R, Cropley I, Hopkins S, Lester R, Martin D, Marshall N, Mepham S, Warren S, Rodger A. Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. Lancet Infect Dis. 2015 Nov;15(11):1300-4. doi: 10.1016/S1473-3099(15)00228-5. Epub 2015 Aug 25. — View Citation

Mbala-Kingebeni P, Aziza A, Di Paola N, Wiley MR, Makiala-Mandanda S, Caviness K, Pratt CB, Ladner JT, Kugelman JR, Prieto K, Chitty JA, Larson PA, Beitzel B, Ayouba A, Vidal N, Karhemere S, Diop M, Diagne MM, Faye M, Faye O, Aruna A, Nsio J, Mulangu F, Mukadi D, Mukadi P, Kombe J, Mulumba A, Villabona-Arenas CJ, Pukuta E, Gonzalez J, Bartlett ML, Sozhamannan S, Gross SM, Schroth GP, Tim R, Zhao JJ, Kuhn JH, Diallo B, Yao M, Fall IS, Ndjoloko B, Mossoko M, Lacroix A, Delaporte E, Sanchez-Lockhart M, Sall AA, Muyembe-Tamfum JJ, Peeters M, Palacios G, Ahuka-Mundeke S. Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment. Lancet Infect Dis. 2019 Jun;19(6):648-657. doi: 10.1016/S1473-3099(19)30118-5. Epub 2019 Apr 15. — View Citation

Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25. — View Citation

Moekotte AL, Huson MA, van der Ende AJ, Agnandji ST, Huizenga E, Goorhuis A, Grobusch MP. Monoclonal antibodies for the treatment of Ebola virus disease. Expert Opin Investig Drugs. 2016 Nov;25(11):1325-1335. doi: 10.1080/13543784.2016.1240785. Epub 2016 Oct 8. — View Citation

Sullivan N, Yang ZY, Nabel GJ. Ebola virus pathogenesis: implications for vaccines and therapies. J Virol. 2003 Sep;77(18):9733-7. doi: 10.1128/jvi.77.18.9733-9737.2003. No abstract available. — View Citation

* Note: There are 11 references in all — Click here to view all references

External Links

•   Institut National pour la Recherche Biomedicale
•   Ridgeback Biotherapeutics (corporate website)
•   WHO: Guidance for managing ethical issues in infectious disease outbreaks
•   WHO: Notes for the record: Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola Virus Disease (EVD)