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Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

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ClinicalTrials.gov Identifier: NCT03167242
Recruitment Status : Recruiting
First Posted : May 25, 2017
Last Update Posted : June 10, 2019
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

This study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated P. falciparum malaria.

There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.


Condition or disease Intervention/treatment Phase
Acute Uncomplicated Plasmodium Falciparum Malaria Drug: KAF156 and LUM-SDF Drug: Coartem Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 512 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Interventional, Multicenter, Randomized Open Label Study to Determine the Effective and Tolerable Dose of KAF156 and Lumefantrine Solid Dispersion Formulation in Combination, Given Once Daily for 1, 2 and 3-days to Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Actual Study Start Date : August 2, 2017
Estimated Primary Completion Date : September 26, 2019
Estimated Study Completion Date : September 22, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: KAF156 400 mg and LUM-SDF 960 mg once daily (QD) for 1 day
Cohort 1
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Experimental: KAF156 800 mg and LUM-SDF 960 mg QD for 1 day
Cohort 2
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Experimental: KAF156 400 mg and LUM-SDF 960 mg QD for 2 days
Cohort 3
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Experimental: KAF156 200 mg and LUM-SDF 480 mg QD for 3 days
Cohort 4
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Experimental: KAF156 400 mg and LUM-SDF 480 mg QD for 3 days
Cohort 5
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Experimental: KAF156 400 mg and LUM-SDF 960 mg QD for 3 days
Cohort 6
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.

Active Comparator: Coartem twice a day (BID) for 3 days
Cohort 7
Drug: Coartem
Control arm

Experimental: KAF156 200 mg and LUM-SDF 960 mg once daily for 1 day
PK Run-in Cohort
Drug: KAF156 and LUM-SDF
Exploration of different dose combinations of KAF156 and LUM-SDF. In Part B, up to three arms will be repeated in children 2 to 12 Years to confirm safety and efficacy from Part A.




Primary Outcome Measures :
  1. PCR-corrected adequate clinical and parasitological response (ACPR) [ Time Frame: Day 28 post-dose ]

Secondary Outcome Measures :
  1. Adverse events (AE) incidence and severity, liver and kidney function tests and electrocardiogram (ECG) abnormalities [ Time Frame: Up to Day 42 post-dose ]
  2. PCR-uncorrected ACPR [ Time Frame: Days 14, 28 and 42 post-dose ]
  3. PCR-corrected ACPR [ Time Frame: Days 14 and 42 post-dose ]
  4. Incidence rate of recrudescence and reinfection [ Time Frame: Days 14, 28 and 42 post-dose ]
  5. Parasite and fever clearance times [ Time Frame: Up to Day 42 post-dose ]
  6. Proportion of patients with parasitaemia [ Time Frame: 12, 24 and 48 hours after treatment ]
  7. Maximum Peak Observed Concentration (Cmax) [ Time Frame: Up to Day 15 post-dose ]
  8. Area Under the Curve (AUC) [ Time Frame: Up to Day 15 post-dose ]
  9. Time after administration of a drug when the maximum plasma concentration is reached (Tmax) [ Time Frame: Up to Day 15 post-dose ]
  10. Half-life (T½) [ Time Frame: Up to Day 15 post-dose ]


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included.
  • Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.
  • P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/µL at the time of pre-screening (i.e., Study Visit 1).
  • Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.3 ºC; or similar history of fever during the previous 24 hours (history of fever must be documented).
  • Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines.

Exclusion Criteria:

  • Mixed Plasmodium infections.
  • Signs and symptoms of severe malaria according to WHO (World Health Organization) 2015 criteria unless characterized by high parasitaemia only.
  • Patients with concurrent febrile illnesses (e.g., typhoid fever).
  • Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the study or severe diarrhea defined as more than 3 watery stools per day.
  • Pregnant or nursing (lactating) women.
  • Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia.
  • Anemia (Hemoglobin level < 8 g/dL).
  • Patients with prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is unknown).
  • History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc (heart rate-corrected QT) interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease.
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory evidence of any of the following:
  • AST/ALT > 2 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
  • AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN
  • Total bilirubin > 2 x ULN, regardless of the level of AST/ALT

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03167242


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Burkina Faso
Novartis Investigative Site Recruiting
Nanoro, Burkina Faso
Gabon
Novartis Investigative Site Recruiting
Lambarene, Gabon
Gambia
Novartis Investigative Site Recruiting
Banjul, Gambia, 273
Kenya
Novartis Investigative Site Recruiting
Kombewa, Kenya
Novartis Investigative Site Recruiting
Siaya, Kenya, 2300
Mali
Novartis Investigative Site Recruiting
Sotuba, Mali
Mozambique
Novartis Investigative Site Recruiting
Chokwe, Mozambique
Thailand
Novartis Investigative Site Completed
Ratchabari, Thailand, 70180
Novartis Investigative Site Completed
Tak, Thailand, 63140
Uganda
Novartis Investigative Site Recruiting
Masaka, Uganda
Novartis Investigative Site Recruiting
Tororo, Uganda
Vietnam
Novartis Investigative Site Recruiting
Binh Phuoc Province, VNM, Vietnam, 830000
Novartis Investigative Site Recruiting
Ho Chi Minh, Vietnam
Sponsors and Collaborators
Novartis Pharmaceuticals
Medicines for Malaria Venture
Investigators
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Study Director: Study Director Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03167242     History of Changes
Other Study ID Numbers: CKAF156A2202
First Posted: May 25, 2017    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artemether, Lumefantrine Drug Combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents