Cohort Event Monitoring Study of Pyramax®

Phase IIIb/IV Cohort Event Monitoring Study To Evaluate, In Real Life Setting, The Safety And Tolerability In Malaria Patients Of The Fixed-Dose Artemisinin-Based Combination Therapy Pyramax®

The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (<1 year of age).

Study Overview

• Status: Completed
• Conditions: Malaria,Falciparum
• Intervention / Treatment: Drug: pyronaridine artesunate

Detailed Description

This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s >2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs >2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics.

An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs >2xULN for follow up of liver function. A cohort of at least 2% of children who are <1 year of age will be included for monitoring of liver function.

• Study Type: Interventional
• Enrollment (Actual): 8572
• Phase: Phase 4

Contacts and Locations

Study Locations

• Cameroon
  • Yaoundé, Cameroon
    • The Biotechnology Center Nkolbisson, Univ of Yaounde I, Messa
• Congo
  • Brazzaville, Congo
    • Centre de Santé FCRM, Hospital of Talangai
• Congo, The Democratic Republic of the
  • Kinshasa, Congo, The Democratic Republic of the, XI
    • Centre de Recherche du Centre Hospitalier du Mont Amba
• Côte D'Ivoire
  • Bouaké, Côte D'Ivoire, BP 1500
    • Institut Pierre Richet / Institut National de SanPublique (IPR/INSP)
• Gabon
  • Lambaréné, Gabon, BP 118
    • CERMEL, Albert Schweitzer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:

  • Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children.
  • Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis).
• Weight ≥5 kg - < 20 kg (granules); ≥20 kg (tablets).
• Ability to take an oral medication.
• Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
• The patient has to comply with all scheduled follow-up visits.

Exclusion Criteria:

• Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4).
• Known allergy to artemisinin and/or to pyronaridine.
• Known pregnancy.
• Lactating women should be excluded if other anti-malarial treatments are available.
• Complicated malaria as per WHO definition (Annex 2)
• Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study.
• Patients having been treated with Pyramax in the previous 28 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pyramax; Pyronaridine artesunate tablets (180/60mg) and granules (60/20mg)	Drug: pyronaridine artesunate; Antimalarial treatment; Other Names: Pyramax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation and identification of hepatic safety events, including raised liver function tests	Evaluation and identification of hepatic safety events (including raised liver function tests - LFTs) of Pyramax in a sub group of malaria patients enrolled with LFTs >2xUL.	Assessment up to Day 28.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall safety	Evaluation of the adverse event reporting of Pyramax in the treatment of uncomplicated malaria under real life conditions.	Assessment up to Day 28.
Evaluation of Efficacy	Evaluation of the efficacy based on crude Day 28 cure rate by species and PCR adjusted cure rate for Day 28 cure rate for P. falciparum of Pyramax in the treatment of uncomplicated malaria under real life conditions	Assessment up to Day 28.

Collaborators and Investigators

• Sponsor: Shin Poong Pharmaceutical Co. Ltd.
• Collaborators: Medicines for Malaria Venture
• Investigators: Principal Investigator: Michael Ramharter, MD, DTM&H, CERMEL, University of Tübingen, Germany

Publications and helpful links

General Publications

• Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, Ramharter M, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma. PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009511. doi: 10.1371/journal.pntd.0009511. eCollection 2021 Jun. Erratum In: PLoS Negl Trop Dis. 2022 Jun 2;16(6):e0010512.
• Tona Lutete G, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, Ntoumi F, Agnandji ST, Groger M, Shin J, Borghini-Fuhrer I, Arbe-Barnes S, Allen SJ, Kremsner PG, Miller R, Duparc S, Ramharter M; CANTAM study group. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study. PLoS Med. 2021 Jun 15;18(6):e1003669. doi: 10.1371/journal.pmed.1003669. eCollection 2021 Jun.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2017
• Primary Completion (ACTUAL): April 10, 2019
• Study Completion (ACTUAL): April 10, 2019

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (ACTUAL): June 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 25, 2019
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Pyramax; Uncomplicated Malaria; Pyronaridine artesunate
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate; Pyronaridine
• Other Study ID Numbers: SP-C-021-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No