Trial of DB289 for the Treatment of Stage I African Trypanosomiasis

• ClinicalTrials.gov Identifier: NCT00803933
• Recruitment Status: Completed
• First Posted: December 8, 2008
• Last Update Posted: December 8, 2008
• Sponsor: Immtech Pharmaceuticals, Inc
• Collaborator: Bill and Melinda Gates Foundation
• Information provided by: Immtech Pharmaceuticals, Inc

Study Description

Brief Summary:

Human African Trypanosomiasis or sleeping sickness has made a spectacular return during the last decade, and in many places the demand largely surpasses the capacities of the treatment centers. Treatment of the disease remains unsatisfactory. All currently used drugs must be administered parenterally, treatment is lengthy, and adverse drug reactions frequent. There are currently no drugs that are easily administered and have low toxicity, and might thus be used as tools to support disease control.

This study aims to compare the safety and efficacy of DB289, a new, orally administered dication prodrug to pentamidine i.m. injection for the treatment of first stage sleeping sickness. The project will be executed in the framework of an international consortium consisting of several partners from academia, industry and from the Democratic Republic of Congo Ministries of Health.

Condition or disease	Intervention/treatment	Phase
African Trypanosomiasis	Drug: DB289; Drug: Pentamidine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II b Trial of DB289 for the Treatment of Stage I African Trypanosomiasis
• Study Start Date: February 2003
• Actual Primary Completion Date: February 2004
• Actual Study Completion Date: June 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: DB289; Pafuramidine maleate (DB289), 100 mg BID orally	Drug: DB289; Pafuramidine maleate (DB289), 100 mg BID orally; Other Name: pafuramidine maleate
Active Comparator: Pentamidine; Pentamidine isethionate (Aventis) for injection (200 mg/vial), 4 mg/kg QD IM	Drug: Pentamidine; Pentamidine isethionate (Aventis) for injection (200 mg/vial), 4 mg/kg QD IM

Outcome Measures

Primary Outcome Measures :

1. The primary efficacy endpoint was the parasitological cure at 3 months after completion of treatment. [ Time Frame: 3 months ]
2. The primary outcome measure for safety analysis was the rate of occurrence of Grade 3 or higher adverse events during the observation period. [ Time Frame: 12 day ]

Secondary Outcome Measures :

1. The secondary outcome measure was the incidence rate of adverse events (all Grades combined) during the 7- to 9-day observation period in Treatment Sequence 1 and during the 12-day observation period in Treatment Sequence 2. [ Time Frame: 12 day ]
2. The number and percentage of subjects with parasitological cure, subjects with confirmed (parasitological) treatment failure, and subjects with suspected treatment failure at 6, 12, and 24 months after completion of treatment. [ Time Frame: 6, 12, 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The patient has early stage T. b. gambiense infection i.e. parasitologically confirmed infection in the blood or lymph node aspirate and greater than or equal to 5 WBC mm-3 detected in the CSF by microscopic examination
2. Patient is 15 to 50 years old
3. Patient has a minimal weight of 35 kilograms

4. If the patient is female of child bearing potential (a women will be considered of non-child bearing potential only if she has been post menopausal for over 2 years or has had a hysterectomy):

   1. she is not lactating,
   2. she had a negative urine pregnancy test result within 24 hours prior to DB289 treatment and
   3. she agrees to use a medically proven method of contraception (abstinence from sexual intercourse is an acceptable method) from the day of consent on until the end of the observation period (day 7).
5. Patient has understood and signed the Informed Consent. If the patient is minor, a legal guardian has signed the Informed Consent

Exclusion Criteria:

1. The patient has late stage T.b. gambiense infection i.e. presence of parasite in the CSF upon microscopic examination or a WBC count of > 5mm-1
2. Active clinically relevant medical conditions that in the Investigator opinion may jeopardize subject safety or interfere with participation in the study, including but not limited to: significant liver diseases, chronic pulmonary diseases, significant cardiovascular diseases, diabetes, thyroid diseases, gout, infection including known HIV infection, CNS trauma or seizure disorders (A list of typical signs and symptoms is provided for guidance of the investigator in attachment 1)
3. Coma Score of less than 9 on the Glasgow Coma Scale (Appendix 8)
4. Withdrawal of consent at any time during the study
5. Any condition which compromises ability to communicate with the investigator as required for the completion of this study.
6. The subject has been previously treated for African Trypanosomiasis.
7. The subject has been previously enrolled in the study. -

Contacts and Locations

Locations

Congo

CDTC Maluku

Gombe, Kinshasa, Congo

Vanga Hospital

Gombe, Kinshasa, Congo

Sponsors and Collaborators

Immtech Pharmaceuticals, Inc

Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Victor Kande, MD; Programme Nationale de Lutte contre la Trypanosomiase Humaine Africaine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Burri C, Yeramian PD, Allen JL, Merolle A, Serge KK, Mpanya A, Lutumba P, Mesu VK, Bilenge CM, Lubaki JP, Mpoto AM, Thompson M, Munungu BF, Manuel F, Josenando T, Bernhard SC, Olson CA, Blum J, Tidwell RR, Pohlig G. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies. PLoS Negl Trop Dis. 2016 Feb 16;10(2):e0004362. doi: 10.1371/journal.pntd.0004362. eCollection 2016 Feb.

• Responsible Party: Christian Burri, Study Director, Swiss Tropical Institute
• ClinicalTrials.gov Identifier: NCT00803933
• Other Study ID Numbers: 289-C-006
• First Posted: December 8, 2008
• Last Update Posted: December 8, 2008
• Last Verified: December 2008

Keywords provided by Immtech Pharmaceuticals, Inc:

first stage; Trypanosoma brucei gambiense; T. b. gambiense; sleeping sickness; First stage T. b. gambiense sleeping sickness

Additional relevant MeSH terms:

Trypanosomiasis; Trypanosomiasis, African; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Pentamidine; Pafuramidine; Antifungal Agents; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents