Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria.

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02083380
• Date of registration: 07/03/2014
• Prospective Registration: Yes
• Primary sponsor: Medicines for Malaria Venture
• Public title: Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria.
• Scientific title: Randomised Phase IIb Study of Efficacy, Safety, Tolerability & Pharmacokinetics of a Single Dose Regimen of Artefenomel (OZ439) in Loose Combination With Piperaquine in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria.
• Date of first enrolment: July 2014
• Target sample size: 448
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02083380
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

Benin, Burkina Faso, Colombia, Congo, The Democratic Republic of the, Gabon, Mozambique, Uganda, Vietnam

Contacts

• Name: Fiona Macintyre, PhD
• Affiliation: Medicines for Malaria Venture (MMV)

• Name: Michael Ramharter, MD
• Affiliation: CERMEL (Centre de Recherches Médicale de Lambaréné)

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female patient age >6 months <70 years.

2. Body weight >5 kg <90 kg.

3. Presence of mono-infection of P. falciparum with:

1. Fever, as defined by axillary temperature = 37.5°C or oral/rectal/tympanic
temperature = 38°C, or history of fever in the previous 24 hours (history of
fever must be documented) and,

2. Microscopically confirmed parasite infection, in range 1,000 to 100,000 asexual
parasites /µL of blood.

4. Written informed consent provided by the adult patient, or parent or legally
acceptable representative (LAR) of the minor patient or by an impartial witness (if
the patient or patient's LAR is illiterate), and by the medically qualified
Investigator. Children will be asked to provide assent where appropriate. The age from
which this will be sought will be defined by local legislation.

Exclusion Criteria:

1. Presence of severe malaria (according to World Health Organization (WHO) definition -
WHO 2013)

2. Anti-malarial treatment:

1. With piperaquine -based compound, mefloquine, naphthoquine or
sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their
inhibition of new infections has fallen below 50%).

2. With amodiaquine or chloroquine within the previous 4 weeks.

3. With quinine, halofantrine, lumefantrine-based compounds and any other
anti-malarial treatment or antibiotics with anti-malarial activity (including
cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin)
within the past 14 days.

4. With any herbal products or traditional medicines, within the past 7 days.

3. Known history or evidence of clinically significant disorders such as, respiratory
(including active tuberculosis), hepatic, renal, gastrointestinal, immunological,
neurological (including auditory), endocrine, infectious, malignancy, psychiatric,
history of convulsions or other abnormality (including head trauma).

4. Family history of sudden death or of congenital or clinical conditions known to
prolong QTcB or QTcF interval or e.g. patients with a history of symptomatic cardiac
arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.

5. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.

6. Any predisposing cardiac conditions for arrhythmia such as severe hypertension, left
ventricular hypertrophy (including hypertrophic cardiomyopathy) or congestive cardiac
failure accompanied by reduced left ventricle ejection fraction.

7. Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia.

8. Any treatment which can induce a lengthening of QT interval, such as:

1. Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide,
procainamide, quinidine, hydroquinidine, sotalol),

2. Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine,
haloperidol, mesoridazine, pimozide, or thioridazine),

3. Anti-depressive agents, certain antimicrobial agents, including agents of the
following classes macrolides (e.g. erythromycin, clarithromycin),
fluoroquinolones (e.g. moxifloxacin, sparfloxacin), imidazole and triazole
antifungal agents, and also pentamidine and saquinavir,

4. Certain non-sedating antihistamines (e.g. terfenadine, astemizole, mizolastine),
cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl,
methadone, vinca alkaloids, arsenic trioxide.

5. Anti-emetics with known QT prolongation potential such as domperidone

9. Mixed Plasmodium infection

10. Severe vomiting, defined as more than three times in the 24 hours prior to enrolment
in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3
or more watery stools per day

11. Severe malnutrition (defined for subjects aged ten years or less as the
weight-for-height being below -3 standard deviation or less than 70% of median of the
National Centre for Health Statistics (NCHS)/WHO normalised reference values, and for
subjects aged greater than ten years, a body mass index (BMI) of less than 16 (WFP
Manual, Chapter 1)).

12. Known history of hypersensitivity, allergic or adverse reactions to piperaquine or
other aminoquinolones or to OZ439 or OZ277

13. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or
Hepatitis C antibody (HCV Ab).

14. If Total Bilirubin is normal, exclude the patient if liver function tests Aspartate
transaminase (AST)/ Alanine transaminase (ALT) = 2x Upper limit of normal (ULN).

15. If Total Bilirubin is > 1 and = 1.5xULN, exclude the patient if AST/ALT >1.5xULN.

16. Total Bilirubin > 1.5XULN

17. Haemoglobin level below 8 g/dL.

18. Serum creatinine levels =2 x ULN

19. 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 not
to become pregnant during the study period and safety follow-up period.

20. Have received an investigational drug within the past 4 weeks.

21. Previous participation in any malaria vaccine study or received malaria vaccine in any
other circumstance.



Age minimum: 6 Months
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Uncomplicated Plasmodium Falciparum Malaria

Intervention(s)

Drug: Artefenomel 800mg: piperaquine 1440mg

Drug: Artefenomel 800mg: piperaquine 960mg

Drug: Artefenomel 800mg: piperaquine 640mg

Primary Outcome(s)

PCR-adjusted ACPR at Day 28 in the PP Population (All Patients) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>2 to <= 5 Years) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Africa (All Ages) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Africa (< = 5 Years) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>= 0.5 to <= 2 Years) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Africa (> Than 5 Years) [Time Frame: Day 28]

PCR-adjusted ACPR at Day 28 in the PP Population: Asia (All Ages) [Time Frame: Day 28]

Secondary Outcome(s)

Crude ACPR at Day 42 in the ITT Population [Time Frame: Day 42]

Crude ACPR at Day 63 in the ITT Population [Time Frame: Day 63]

Parasite Clearance Time [Time Frame: 0, 6, 12, 18, 24, 30, 36, 48 and 72 hours post dose]

Crude ACPR at Day 63 in the PP Population [Time Frame: Day 63]

PRR48 [Time Frame: 0, 6, 12, 18, 24, 30, 36 and 48 hours post dose]

Crude ACPR at Day 28 in the PP Population [Time Frame: Day 28]

PCR - Adjusted ACPR at Day 42 in the PP Population [Time Frame: Days 42]

Kaplan-Meier Estimate of Recrudescence [Time Frame: Day 63]

Kaplan-Meier Estimate of Recurrence [Time Frame: Day 63]

PCR-adjusted ACPR at Day 28 in the ITT Population [Time Frame: Day 28]

PCR-adjusted ACPR at Day 42 in the ITT Population [Time Frame: Day 42]

PCR-adjusted ACPR at Day 63 in the ITT Population [Time Frame: Day 63]

Fever Clearance Time [Time Frame: Day 42]

Kaplan-Meier Estimate of New Infection Rate [Time Frame: Day 63]

Crude ACPR at Day 28 in the ITT Population [Time Frame: Day 28]

Crude ACPR at Day 42 in the PP Population [Time Frame: Day 42]

PCR-adjusted ACPR at Day 63 in the PP Population [Time Frame: Day 63]

Secondary ID(s)

MMV_OZ439_13_003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/01/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02083380