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Safety of KAE609 in Adults With Uncomplicated Plasmodium Falciparum Malaria.

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ClinicalTrials.gov Identifier: NCT03334747
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses.

This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients.


Condition or disease Intervention/treatment Phase
Malaria Drug: KAE609 Drug: Coartem Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-center, Randomized, Open-label, Dose-escalation Study to Determine Safety of Single (QD) and Multiple (3 QD) Doses of KAE609, Given to Adults With Uncomplicated Plasmodium Falciparum Malaria.
Actual Study Start Date : November 16, 2017
Estimated Primary Completion Date : May 13, 2019
Estimated Study Completion Date : May 14, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Treatment arm 1: KAE609 10 mg Single Dose (SD)
COHORT 1_Treatment arm 1: KAE609 10 mg once daily (QD) for 1 day
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Active Comparator: Treatment arm 2:Coartem Control
COHORT 1_Treatment arm 2: Coartem® twice a day (BID) for 3 days
Drug: Coartem
Control Arm

Experimental: Treatment arm 3:KAE609 25 mg SD
COHORT 2_Treatment arm 3: KAE609 25 mg once daily (QD) for 1 day
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Experimental: Treatment arm 4:KAE609 10 mg 3 Days
COHORT 2_Treatment arm 4: KAE609 10 mg (QD) for 3 days
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Active Comparator: Treatment arm 5:Coartem Control
COHORT 2_Treatment arm 5: Coartem® twice a day (BID) for 3 days
Drug: Coartem
Control Arm

Experimental: Treatment arm 6:KAE609 50 mg SD
COHORT 3_Treatment Arm 6: KAE609 50 mg once daily (QD) for 1 day
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Experimental: Treatment arm 7:KAE609 25 mg 3 Days
COHORT 3_Treatment Arm 7: KAE609 25 mg once daily (QD) for 3 days
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Active Comparator: Treatment arm 8:Coartem Control
COHORT 3_Treatment arm 8: Coartem® twice a day (BID) for 3 days
Drug: Coartem
Control Arm

Experimental: Treatment arm 9:KAE609 75 mg SD
COHORT 4_Treatment Arm 9: KAE609 75 mg once daily (QD) for 1 day
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Experimental: Treatment arm 10:KAE609 50 mg 3 Days
COHORT 4_Treatment Arm 10: KAE609 50 mg once daily (QD) for 3 days
Drug: KAE609
Exploration of different doses of KAE609 to establish safety profile.

Active Comparator: Treatment arm 11:Coartem Control
COHORT 4_Treatment Arm 11: Coartem® twice a day (BID) for 3 days
Drug: Coartem
Control Arm




Primary Outcome Measures :
  1. At least 2 CTCAE grades increase from baseline in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the 4 week study period [ Time Frame: Upto day 29 post dose ]

    ≥ 2 Grade (CTCAE grades) increase from baseline (at any time point during the study) in:

    • 2 patients in a 10 patient cohort (Cohorts 1 and 2) or
    • 3 patients in a 20 patient cohort (Cohorts 3 and 4) If above situation occurs, suspend recruitment and initiate review of liver safety (and any other relevant data) by safety review committee.Any further progression of the study is based on the decision by the safety review committee


Secondary Outcome Measures :
  1. Polymerase Chain Reaction (PCR) corrected Clinical and Parasitological Cure [ Time Frame: 15 and 29 days post dose ]
    PCR-Corrected at Days 15 and 29 (i.e., 14 and 28 days post-dose)

  2. Recrudescence [ Time Frame: Upto day 29 post dose ]
    Time to recrudescence will be calculated from the time of first study medication to the date of first event if a patient experience the event and be censored at the time of last parasite assessment if a patient does not experience the event.

  3. Parasite Clearance Time [ Time Frame: Upto Day 29 ]
    Descriptive statistics will be presented for each treatment by Cohort. In case that a patient receives rescue medication before (parasite ) clearance, the time to event will be censored at the first use of rescue medication.

  4. Proportion of patients with parasitaemia [ Time Frame: At 12, 24 and 48 hours post dose ]
    This will be determined using uncorrected parasite count.

  5. Maximum Peak Observed Concentration (Cmax) [ Time Frame: Upto day 15 post dose ]
  6. Area under the curve (AUC) [ Time Frame: Upto day 15 post dose ]
  7. Time after administration of a drug when the maximum plasma concentrations is reached (Tmax) [ Time Frame: Upto day 15 post dose ]
  8. Half-life (T½) [ Time Frame: Upto day 15 post dose ]
  9. Uncorrected Adequate Clinical and Parasitological Response [ Time Frame: 15 and 29 days post dose ]
    PCR-Uncorrected adequate clinical and parasitological response (ACPR) at Days 15 and 29 (i.e., 14 and 28 days post-dose)

  10. Fever Clearance Time [ Time Frame: Upto Day 29 ]
    Descriptive statistics will be presented for each treatment by Cohort. In case that a patient receives rescue medication before (fever) clearance, the time to event will be censored at the first use of rescue medication.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

KEY Inclusion Criteria:

  1. Male and female patients ≥ 18 years with a body weight ≥ 45 kg.
  2. Microscopic confirmation of acute uncomplicated P. falciparum using by Giemsa-stained thick film.
  3. P. falciparum parasitaemia of 500 to 50 000 parasites/µL.
  4. Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
  5. Written informed consent must be obtained before any study assessment is performed. If the patient is unable to write, then a witnessed consent according to local ethical standards is permitted.

KEY Exclusion Criteria:

  1. Mixed Plasmodium infections.
  2. Signs and symptoms of severe malaria according to World Health Organization (WHO) 2016 criteria (WHO 2016).
  3. Known liver abnormalities, liver cirrhosis (compensated or decompensated), known active or history of hepatitis B or C (testing not required), known gallbladder or bile duct disease, acute or chronic pancreatitis.
  4. Clinical or laboratory evidence of any of the following:
  5. AST/ALT > 1.5 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
  6. AST/ALT > 1.0 and ≤ 1.5 x ULN and total bilirubin is > ULN
  7. Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
  8. History of photodermatitis/increased sensitivity to sun.
  9. Pregnant or nursing (lactating) women.
  10. Known disturbances of electrolyte balance, e.g. hypokalemia, hypocalcemia or hypomagnesemia.
  11. Moderate to severe anemia (Hemoglobin level <8 g/dL).

Other protocol-defined inclusion/exclusion criteria may apply


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): NCT03334747


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

Locations
Ghana
Novartis Investigative Site Recruiting
Kintampo, Ghana
Novartis Investigative Site Recruiting
Navrongo, Ghana
Mali
Novartis Investigative Site Recruiting
Bamako, Mali
Uganda
Novartis Investigative Site Recruiting
Kampala, Uganda
Novartis Investigative Site Recruiting
Tororo, Uganda
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03334747     History of Changes
Other Study ID Numbers: CKAE609A2202
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
uncomplicated Plasmodium falciparum Malaria.

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artemether-lumefantrine combination
Artemisinins
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents