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A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)

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Ce qui est testé

CD4 Antigens

+ Zidovudine
Médicament
Qui peut participer

HIV Infections

À partir de 13 ans
Comment se déroule l'étude

Étude thérapeutique

Phase 2
Interventionnel

Résumé

Sponsor principalNational Institute of Allergy and Infectious Diseases (NIAID)
Dernière mise à jour : 14 mars 2011
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Part 1A: To find the dose of zidovudine (AZT) that causes less than a 50 percent drop in HIV-1 p24 antigen levels in patients with AIDS and advanced AIDS related complex (ARC); to determine the pharmacokinetics (blood levels) of rsCD4 administered in combination with AZT. Parts 1B and 2: To test for additive or synergistic activity between rsCD4 and AZT as judged by falls in HIV-1 p24 antigen levels; and to evaluate the safety of rsCD4 and AZT in patients with AIDS and advanced ARC. AZT has been shown to be effective in the treatment of AIDS and advanced ARC but not without toxicity. The most clinically significant toxicity is dose related inhibition of bone marrow function. Furthermore, HIV-1 isolates from patients treated for more than 6 months with AZT have now been found which appear to have reduced sensitivity to AZT. The incidence of toxicity and occurrence of virus with reduced sensitivity to AZT may result in the inability to administer AZT long-term to patients with AIDS and advanced ARC. Recombinant soluble CD4 (rCD4) has shown antiretroviral effects and has been shown to be safe when given to AIDS and ARC patients either as a single agent or in combination with AZT. AZT has been shown to be effective in the treatment of AIDS and advanced ARC but not without toxicity. The most clinically significant toxicity is dose related inhibition of bone marrow function. Furthermore, HIV-1 isolates from patients treated for more than 6 months with AZT have now been found which appear to have reduced sensitivity to AZT. The incidence of toxicity and occurrence of virus with reduced sensitivity to AZT may result in the inability to administer AZT long-term to patients with AIDS and advanced ARC. Recombinant soluble CD4 (rCD4) has shown antiretroviral effects and has been shown to be safe when given to AIDS and ARC patients either as a single agent or in combination with AZT. Part 1A: Twenty p24+ patients with AIDS or advanced ARC are randomized to 4 dosing groups of 5 patients each. Patients are treated with AZT for 6 weeks at ranging doses to determine a minimally effective dose (MED). At the end of week 6, each patient is sequentially assigned to 1 of 5 groups of rCD4 / AZT combination treatment. The first 3 patients to complete treatment through week 6 are treated in group A, the next 3 patients in group B, and so on. The treatment period is 4 weeks. Each patient continues on his or her AZT dose as initially administered. The highest dose of AZT that produces less than a 50 percent drop in HIV-1 p24 antigen levels in at least 3 of 5 patients over 6 weeks will be the MED of AZT and will be known as the AZT MED. After the MED is determined, Part 1B begins. Part 1B: 20 patients are randomized to 2 different dosing groups: Group 5: AZT MED (weeks 1 to 8), then AZT MED plus rCD4 (weeks 9 to 16); Group 6: AZT MED plus rCD4 (weeks 1 to 8), then AZT MED (weeks 9 to 16). Part 2: Part 2 begins once accrual to Part 1B is completed. If fewer than 10 of 20 patients exhibit a drop of at least 50 percent in p24 antigen level after receiving AZT and rsCD4 combination treatment, entry to Part 2 will be interrupted and the study design will be reevaluated. In Part 2, 10 patients are randomly assigned to one of four groups. Patients within each group receive two 8 week treatment courses. These two treatment courses are 8 weeks with the AZT MED alone, and 8 weeks of treatment with the combination of the AZT MED plus rCD4.

Titre officielA Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC) 
Sponsor principalNational Institute of Allergy and Infectious Diseases (NIAID)
Dernière mise à jour : 14 mars 2011
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Protocole

Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.
Détails du design
80 participants à inclureNombre total de participants que l'essai clinique vise à recruter.
Traitement
Cette étude teste un ou plusieurs traitements pour évaluer leur efficacité contre une maladie ou un problème de santé spécifique. L'objectif est de voir si un nouveau médicament ou une thérapie fonctionne mieux, ou provoque moins d'effets secondaires que les options existantes.

Comment la nature du traitement est tenue confidentielle
Dans une étude en ouvert, tous les participants ainsi que les chercheurs savent quel traitement est administré. Ce type de protocole est utilisé lorsqu'il n'est pas nécessaire ou pas possible de masquer les traitements.

Autres méthodes de masquage
Simple aveugle
: les participants ignorent le traitement reçu, mais les chercheurs le connaissent.

Double aveugle
: ni les participants ni les chercheurs ne savent quel traitement est administré.

Triple aveugle
: Les participants, les chercheurs et les personnes qui analysent les résultats ne savent pas quel traitement est administré.

Quadruple aveugle
: Les participants, les chercheurs, les personnes qui analysent les résultats et les professionnels de santé en charge du suivi ne savent pas non plus quel traitement est administré.

Éligibilité

Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.
Conditions
Critères
Tout sexeLe sexe biologique des participants éligibles à s'inscrire.
À partir de 13 ansTranche d'âge des participants éligibles à participer.
Volontaires sains non autorisésIndique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.
Conditions
Pathologie
HIV Infections
Critères

Inclusion Criteria Concurrent Medication: Allowed: * Nystatin or clotrimazole for suppression of oral thrush. * Aerosolized pentamidine as chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). * Trimethoprim / sulfamethoxazole (TMP / SMX) for patients who are clinically and hematologically stable on TMP / SMX PCP prophylaxis. Patients must have the following: * Diagnosis of AIDS or advanced AIDS related complex (ARC). * CD4 cell count \< 300 cells/mm3. * Ability to understand and sign the consent form. Risk Behavior: Allowed: * History of drug abuse with current abstinence or enrollment in a methadone treatment program. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: * Malignancies other than Kaposi's sarcoma. * AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. * Active infection with an opportunistic pathogen requiring ongoing therapy. * Preexisting antibodies to rCD4. Concurrent Medication: Excluded: * Investigational drugs. * Antiretroviral agents such as dextran sulfate or AL721. * Cytotoxic chemotherapy. Concurrent Treatment: Excluded: * Radiation therapy. Patients with the following are excluded: * Malignancies other than Kaposi's sarcoma. * AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. * Active infection with an opportunistic pathogen requiring ongoing therapy. * Preexisting antibodies to rCD4. Prior Medication: Excluded: * Zidovudine (AZT) for longer than 30 days or prior treatment with AZT for \< 30 days if discontinued for toxicity due to AZT. * Excluded within 30 days of study entry: * Immunomodulators. * Previous participation in any group of another part of this study. For example, patients treated in Part 1A of this study may not reenter the study to be treated in Part 2. * Chemotherapy. Prior Treatment: Excluded within 30 days of study entry: * Radiation therapy. Active use of illicit drugs or abuse of alcohol at time of protocol entry.



Centres d'étude

Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.
Cette étude comporte 2 sites
Suspendu
Tulane Univ School of MedicineNew Orleans, United StatesVoir le site
Suspendu
Bellevue Hosp / New York Univ Med CtrNew York, United States

Suspendu2 Centres d'Étude