Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria

NCT04368910 | Terminated Phase 3 Results DMC

• 1 other identifier: SP-C-008-07
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax (P. vivax) malaria

Conditions

Malaria

Keywords

Artemisinin-based combination therapy (ACT); Pyramax; Pyronaridine artesunate; Chloroquine; Children; Adults; Plasmodium vivax; Republic of Korea

Outcome Measures

Primary Outcomes (1)

• Crude Cure Rate on Day 14

  Percentage of subjects with crude cure rate at Day 14, defined as absence of parasitaemia on Day 14, irrespective of body temperature without previously meeting any of the criteria of treatment failure

  Day 14

Secondary Outcomes (6)

• Crude Cure Rate on Day 28

  Day 28

• Parasite Clearance Time (PCT)

  Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned within the 42-day period)

• Fever Clearance Time (FCT)

  Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit (Days 7, 14, 28 and 42)

• Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3

  Days 1, 2, and 3

• Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3

  Days 1, 2, and 3

Other Outcomes (1)

• Crude Cure Rate on Day 42

  Day 42

Study Arms (2)

Pyronaridine - artesunate

EXPERIMENTAL

Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days. For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.

Drug: Pyronaridine - artesunate

Chloroquine

ACTIVE COMPARATOR

Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days. For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.

Drug: Chloroquine

Interventions

Pyronaridine - artesunate DRUG

Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.

Also known as: Pyramax

Pyronaridine - artesunate

Chloroquine DRUG

Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.

Chloroquine

Eligibility Criteria

• Age: 3 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female patients between the age of 3 and 60 years, inclusive.
• Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
• Presence of acute uncomplicated P. vivax mono-infection confirmed by:
• Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
• Positive microscopy of P. vivax with parasite density ≥250/ μL of blood (including at least 50% of asexual parasites).
• Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
• Ability to swallow oral medication.
• Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.

You may not qualify if:

• Presence of a mixed Plasmodium infection.
• Presence of other clinical condition requiring hospitalization.
• Presence of significant anaemia, as defined by Hb \<8 g/dL.
• Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
• Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
• Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
• Known seropositive HIV antibody.
• Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
• Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
• Have received any investigational drug within the past 4 weeks.
• Liver function tests (AST/ALT levels) \>2.5 times the upper limit of normal range.
• Known significant renal impairment as indicated by serum creatinine levels of \>1.4 mg/dL.
• Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
• Previous participation in the present clinical trial with pyronaridine artesunate.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceuticals: collaborator

Study Sites (2)

Inje University Ilsan Paik Hospital

Goyang-si, 411-706, South Korea

Location

Eulji General Hospital

Seoul, 139-711, South Korea

Location

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Interventions

pyronaridine tetraphosphate, artesunate drug combination; Chloroquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to slow recruitment the study was terminated prematurely by the Sponsor after 30 subjects (of the 40 planned) had been included.

Results Point of Contact

• Title: Stephan Duparc, MD
• Organization: Medicines for Malaria Venture

duparcs@mmv.org

+41 22 555 0300

Study Officials

• Stephan Duparc, MD

  Medicine for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 30, 2020
• Study Start: September 6, 2007
• Primary Completion: October 16, 2010
• Study Completion: November 15, 2010
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2021-11

Locations

KR (2)