Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

NCT03660839 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ACT14655U1111-1191-5573
• Study Type: interventional
• Target: 140
• Locations: 5 countries
• Sites: 7

Brief Summary

Primary Objective: To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor. Secondary Objectives:

• To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.
• To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.
• To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.
• To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.
• To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

Conditions

Plasmodium Falciparum Infection

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)

  ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 \>Day 0 irrespective of AT;or parasitemia on Day 3 with AT\>=37.5 degree Celsius (°C);or parasitemia count on Day 3 \>=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection.

  Day 28

Secondary Outcomes (24)

• Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28

  Day 28

• Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours

  Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours

  Baseline, 24, 48 and 72 hours post-dose

• Time to 50% and 99% Parasite Reduction

  Up to Day 28

• Parasite Clearance Time (PCT)

  From the start of study drug administration up to the time of the first negative blood film (up to Day 28)

Study Arms (4)

Ferroquine 400 milligram (mg)

EXPERIMENTAL

On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.

Drug: Ferroquine (SSR97193)

Ferroquine 400 mg + Artefenomel 300 mg

EXPERIMENTAL

On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.

Drug: Artefenomel (OZ439); Drug: Ferroquine (SSR97193)

Ferroquine 400 mg + Artefenomel 600 mg

EXPERIMENTAL

On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.

Drug: Artefenomel (OZ439); Drug: Ferroquine (SSR97193)

Ferroquine 400 mg + Artefenomel 1000 mg

EXPERIMENTAL

On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.

Drug: Artefenomel (OZ439); Drug: Ferroquine (SSR97193)

Interventions

Artefenomel (OZ439) DRUG

Pharmaceutical form: Granules for oral suspension Route of administration: Oral

Ferroquine 400 mg + Artefenomel 1000 mg; Ferroquine 400 mg + Artefenomel 300 mg; Ferroquine 400 mg + Artefenomel 600 mg

Ferroquine (SSR97193) DRUG

Pharmaceutical form: Capsule Route of administration: Oral

Ferroquine 400 mg + Artefenomel 1000 mg; Ferroquine 400 mg + Artefenomel 300 mg; Ferroquine 400 mg + Artefenomel 600 mg; Ferroquine 400 milligram (mg)

Eligibility Criteria

• Age: 14 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants (14-69 years old inclusive) with body weight within 35 and 90 kilograms (kg), with uncomplicated Plasmodium falciparum (P. falciparum) malaria, with a fever as defined with axillary temperature greater than or equal to (\>=) 37.5 degree Celsius (°C) or oral/ rectal/ tympanic temperature \>=38°C or history of fever in the previous 24 hours (history of fever was documented), with a mono-infection with P. falciparum and parasitemia (microscopically, blood smear) \>= 3,000 and less than or equal to (\<=) 50,000 asexual parasites per microliter of blood.

You may not qualify if:

• Presence of severe malaria.
• Known history or evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, respiratory, endocrine, immunological, infectious, neurological (in particular convulsions), malignancy, psychiatric disease or symptoms which, in the judgment of the investigator, might confuse the interpretation of the safety information.
• Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more watery stools per day.
• Severe malnutrition defined as a body mass index of less than 16 kg per meter square for adults and for children Z-score less than (\<) -3 or weight for age (%) of the median \<60.
• Splenectomized participants or presence of surgical scar on left hypochondrium.
• Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other amino quinolines or to OZ439 or OZ277 or any of the excipients.
• Participant treated with anti-malarial treatment:
• With piperaquine phosphate-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks.
• With amodiaquine or chloroquine within the previous 4 weeks.
• With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.
• With any herbal products or traditional medicines, within the past 7 days.
• Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest, which were: strong Cytochrome P450 (CYP) 2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.
• Any treatment known to induce a prolongation of QT interval.
• Participated in any trial investigating OZ439 and/or FQ compounds.
• Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.

Sponsors & Collaborators

• Sanofi: lead
• Medicines for Malaria Venture: collaborator

Study Sites (7)

Investigational Site Number 2040001

Cotonou, Benin

Location

Investigational Site Number 8540002

Banfora, Burkina Faso

Location

Investigational Site Number 8540001

Ouagadougou, 01 BP218, Burkina Faso

Location

Investigational Site Number 2660002

Lambaréné, Gabon

Location

Investigational Site Number 2660001

Libreville, B.P. 4009, Gabon

Location

Investigational Site Number 4040002

Siaya, Kenya

Location

Investigational Site Number 8000001

Tororo, Uganda

Location

Related Publications (1)

• Gansane A, Lingani M, Yeka A, Nahum A, Bouyou-Akotet M, Mombo-Ngoma G, Kaguthi G, Barcelo C, Laurijssens B, Cantalloube C, Macintyre F, Djeriou E, Jessel A, Bejuit R, Demarest H, Marrast AC, Debe S, Tinto H, Kibuuka A, Nahum D, Mawili-Mboumba DP, Zoleko-Manego R, Mugenya I, Olewe F, Duparc S, Ogutu B. Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria. Malar J. 2023 Jan 3;22(1):2. doi: 10.1186/s12936-022-04420-2.

  PMID: 36597076 DERIVED

MeSH Terms

Interventions

artefenomel; ferroquine

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: September 7, 2018
• Study Start: September 11, 2018
• Primary Completion: November 6, 2019
• Study Completion: November 6, 2019
• Last Updated: March 21, 2022
• Results First Posted: December 2, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); GA (2); UG (1); KE (1); BU (2)