CompletedNCT02806232Updated Nov 20, 2019Results posted

An Open Label Dose Finding Safety and Efficacy in Children and Infants Infected With Schistosomiasis (S.Mansoni)

A Phase 2 interventional study of Biltricide (racemate praziquantel) oral tablets and Racemate Praziquantel ODT in Schistosomiasis, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in Germany. Open to participants aged 3 Months to 6 Years. Per ClinicalTrials.gov, last updated 2019-11-20.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 444
Allocation: Randomized
Ages: 3 Months to 6 Years
Sex: All

Study summary

The Phase II study consisted of two parts, part 1 is open label, randomized, controlled and exploratory dose finding in children aged between 2 and 6 years infected with S. mansoni. Part 2 investigated efficacy and safety with the selected formulation and dosage in S. mansoni infected children aged between 3 months - 2 years.

Conditions studied

Schistosomiasis

Browse trials for

Schistosomiasis 84

Keywords

Praziquantel ODT formulation
Biltricide

Who can participate

Ages eligible: 3 Months to 6 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male and female children aged 2 to 6 years (Part 1) and 3 to 24 months (Part 2)
S. mansoni positive diagnosis defined as positive egg counts in stool (greater than [>]1 egg/1 occasion) according to World Health Organization (WHO) classification : light (1-99 eggs per gram of faeces), moderate (100-399 eggs per gram of faeces) and heavy (greater than or equal to [>=]400 eggs per gram of faeces) infections
Minimum weight of 8.0 kg in 2- to 6-year-old children and of 4.0 kg in 3- to 24-month infants
- Parents/legal representative ability to communicate well with the Investigator, to understand the protocol requirements and restrictions, and willing their children to comply with the requirements of the entire trial, i.e.
To be examined by a study physician at screening and 14-21 days after treatment
To provide stool and urine samples at screening, 24 hours and 8 days after treatment, as well as 14-21 days after treatment
To provide finger prick blood samples for Pharmacokinetics (PK) studies and blood samples for safety assessments

Exclusion criteria

Exclusion Criteria:

Treatment in the 4 weeks prior to study screening with Praziquantel (PZQ) , other anti-helminthic, antimalarial or anti-retroviral compounds or any other medication that might affect the PK of PZQ such as certain antiepileptics (e.g., carbamazepine or phenytoin), glucocorticosteroids (e.g., dexamethasone), chloroquine, rifampicin or cimetidine
For children being breast fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to administration of Investigational medicinal product
Previous history of adverse reactions associated with PZQ treatment
Marked increases of the liver transaminases (alanine aminotransferase and/or aspartate aminotransferase) above 3x Upper Limit of Normal (ULN)
History of acute or severe chronic disease including hepato-splenic schistosomiasis
Fever defined as temperature above 38.0 degree centigrade
Debilitating illnesses such as tuberculosis, malnutrition, etc. as well as a medical history of seizures
Mixed S. haematobium and S. mansoni infections
Findings in the clinical examination of schistosome-infected children participating in the study as performed by the study clinician on the treatment day, that in the opinion of the Investigator constitutes a risk or a contraindication for the participation of the subject in the study or that could interfere with the study objectives, conduct or evaluation
Unlikelihood to comply with the protocol requirements, instructions and trial-related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 444 participants (actual)

Study arms

Experimental
Part 1, Cohort 1: Biltricide (racemate praziquantel) 20 mg/kg
Participants received Biltricide (600 mg tablet) administered orally at a dose of 20 milligram per kilogram (mg/kg), three times a day on treatment Day 1.
Drug: Biltricide (racemate praziquantel) oral tablets
Experimental
Part 1, Cohort 2: Biltricide (racemate praziquantel) 40 mg/kg
Participants received Biltricide (600 mg tablet) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.
Drug: Biltricide (racemate praziquantel) oral tablets
Experimental
Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg
Participants received Racemate Praziquantel oral dispersible tablet (ODT) (150 mg) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.
Drug: Racemate Praziquantel ODT
Experimental
Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg
Participants received Racemate Praziquantel ODT (150 mg) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1.
Drug: Racemate Praziquantel ODT
Experimental
Part 1, Cohort 5: Levo Praziquantel 30 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 30 mg/kg as a single dose on treatment Day 1.
Drug: Levo Praziquantel ODT
Experimental
Part 1, Cohort 6: Levo Praziquantel 45 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 45 mg/kg as a single dose on treatment Day 1.
Drug: Levo Praziquantel ODT
Experimental
Part 1, Cohort 7: Levo Praziquantel 60 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1.
Drug: Levo Praziquantel ODT
Experimental
Part 2, Cohort 8: Levo Praziquantel 50 mg/kg
Participants aged 13-24 months months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1.
Drug: Levo Praziquantel ODT
Experimental
Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Participants aged 3 to 12 months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1.
Drug: Levo Praziquantel ODT

Interventions

DrugBiltricide (racemate praziquantel) oral tablets
Biltricide (600 mg tablet) was administered to participants at a dose of 20 mg/kg in Part 1, Cohort 1 and at a dose of 40mg/kg in Part 1, Cohort 2.
DrugRacemate Praziquantel ODT
Racemate Praziquantel (PZQ) (150) mg was administered at a dose of 40 mg/kg in Part 1, Cohort 3 and at a dose of 60 mg/kg in Part 1, Cohort 4.
DrugLevo Praziquantel ODT
Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.

What researchers measure

Primary outcomes

Number of Participants With Clinical Cure Determined by Kato-Katz Method
Clinical cure was defined as zero egg counts at 14-21 days post treatment as determined by the Kato-Katz method. Number of participants with clinical cure were reported.
Time frame: 14-21 days post treatment

Secondary outcomes

Egg Reduction Rate (Percent)
Percent reduction in egg count was calculated as geometric mean egg count at post-treatment minus geometric mean egg count at baseline (before treatment) divided by geometric mean egg count at baseline.
Time frame: Baseline, 14-21 days post treatment
Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test
Clinical Cure defined as no parasite eggs in the stools as assessed by the commercially available POC-CCA assay for S. mansoni. Number of participants with clinical cure were reported.
Time frame: Day 2, Day 8 and 14-21 days post treatment

Results

Posted Nov 20, 2019

Participant flow

Participant flow — Overall Study
Milestone	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Started	60	60	60	60	60	60	60	20	4
Completed	59	56	59	60	58	58	60	20	4
Not completed	1	4	1	0	2	2	0	0	0
Withdrew: Lost to follow-up	1	2	1	0	0	1	0	0	0
Withdrew: Withdrawal by subject	0	2	0	0	2	1	0	0	0

Outcome measures

PrimaryNumber of Participants With Clinical Cure Determined by Kato-Katz Method

Clinical cure was defined as zero egg counts at 14-21 days post treatment as determined by the Kato-Katz method. Number of participants with clinical cure were reported.

Time frame:: 14-21 days post treatment
Reported as:: Count of participants · Participants

Number of Participants With Clinical Cure Determined by Kato-Katz Method
Participants	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Number of Participants With Clinical Cure Determined by Kato-Katz Method	51	43	47	46	44	49	52	14	4

SecondaryEgg Reduction Rate (Percent)

Percent reduction in egg count was calculated as geometric mean egg count at post-treatment minus geometric mean egg count at baseline (before treatment) divided by geometric mean egg count at baseline.

Time frame:: Baseline, 14-21 days post treatment
Reported as:: Geometric mean · percent reduction in egg count

Egg Reduction Rate (Percent)
percent reduction in egg count	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Egg Reduction Rate (Percent)	94.6 (89.8 to 99.4)	83.3 (74.7 to 91.9)	88.6 (81.8 to 95.4)	88.6 (82.2 to 94.9)	88.3 (81.3 to 95.3)	92.3 (86.4 to 98.1)	94.1 (88.6 to 99.6)	97.7 (92.9 to 100.0)	100.0 (100.0 to 100.0)

SecondaryNumber of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test

Clinical Cure defined as no parasite eggs in the stools as assessed by the commercially available POC-CCA assay for S. mansoni. Number of participants with clinical cure were reported.

Time frame:: Day 2, Day 8 and 14-21 days post treatment
Reported as:: Count of participants · Participants

Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test
Participants	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg
Day 2	8	3	3	8	4	6	11	5
Day 8	28	16	19	18	16	28	38	8
14-21 days post treatment	33	21	24	32	24	35	42	10

Adverse events

Collected over Day 1 to Day 21. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	0/60 (0%)	1/60 (1.7%)	25/60 (41.7%)
Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	0/60 (0%)	0/60 (0%)	30/60 (50%)
Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	0/60 (0%)	1/60 (1.7%)	29/60 (48.3%)
Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	0/60 (0%)	0/60 (0%)	31/60 (51.7%)
Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	0/60 (0%)	0/60 (0%)	28/60 (46.7%)
Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	0/60 (0%)	0/60 (0%)	33/60 (55%)
Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	0/60 (0%)	0/60 (0%)	37/60 (61.7%)
Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	0/20 (0%)	0/20 (0%)	10/20 (50%)
Part 2, Cohort 9: Levo Praziquantel 50 mg/kg	0/4 (0%)	0/4 (0%)	4/4 (100%)

Most frequent serious events

Most frequent serious events
Event	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Transaminases increasedInvestigations	1/60	0/60	1/60	0/60	0/60	0/60	0/60	0/20	0/4

Most frequent other events

Most frequent other events
Event	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
AnaemiaBlood and lymphatic system disorders	15/60	25/60	23/60	22/60	18/60	22/60	29/60	5/20	4/4
MalariaInfections and infestations	5/60	3/60	5/60	1/60	4/60	4/60	2/60	5/20	1/4
C-reactive protein increasedInvestigations	7/60	4/60	10/60	8/60	7/60	14/60	6/60	0/20	0/4
BronchitisInfections and infestations	9/60	7/60	3/60	5/60	4/60	3/60	8/60	2/20	0/4
Abdominal painGastrointestinal disorders	5/60	3/60	3/60	5/60	4/60	0/60	6/60	1/20	0/4

Baseline characteristics

Safety analysis set included all participants who were exposed to investigative medicinal product.

Age, Continuous
Age, Continuous(years)	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg	Total
Mean	4.1 ± 1.3	4.3 ± 1.3	4.4 ± 1.2	4.2 ± 1.2	4.2 ± 1.2	4.3 ± 1.1	4.4 ± 1.3	1.7 ± 0.3	0.6 ± 0.2	4.1 ± 1.3

Sex: Female, Male
Sex: Female, Male(Participants)	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg	Total
Female	22	28	32	35	23	32	25	7	1	205
Male	38	32	28	25	37	28	35	13	3	239

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg	Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg	Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg	Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg	Part 1, Cohort 5: Levo Praziquantel 30 mg/kg	Part 1, Cohort 6: Levo Praziquantel 45 mg/kg	Part 1, Cohort 7: Levo Praziquantel 60 mg/kg	Part 2, Cohort 8: Levo Praziquantel 50 mg/kg	Part 2, Cohort 9: Levo Praziquantel 50 mg/kg	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	60	60	60	60	60	60	60	20	4	444
White	0	0	0	0	0	0	0	0	0	0
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Study locations

1 site

Please Contact the Communication Center
Darmstadt, Germany

References and documents

Study documents

Statistical analysis plan · Jan 31, 2018
Study protocol · Feb 28, 2018

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT02806232
Lead sponsor: Merck KGaA, Darmstadt, Germany
Responsible party: Sponsor
First posted: Jun 20, 2016
Start date: Jun 12, 2016
Primary completion: Oct 30, 2018
Completion: Nov 17, 2018
Results posted: Nov 20, 2019
Last update: Nov 20, 2019

Study contacts

Medical Responsible

study director · Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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