- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01417091
Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
A Randomized, Open Label Intra-patient Dose Escalation Study With an Untreated Reference Group to Evaluate Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Infusions of BPS804 in Adults With Moderate Osteogenesis Imperfecta
This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 in adults with osteogenesis imperfecta (OI).
Pharmacodynamic effect will be determined by serological biomarkers and radiologic assessments. In addition, tolerability and pharmacokinetics (PK) will be evaluated.
Panoramica dello studio
Descrizione dettagliata
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
-
-
Bruxelles, Belgio, 1200
- Novartis Investigative Site
-
Gent, Belgio, 9000
- Novartis Investigative Site
-
-
-
-
Quebec
-
Montreal, Quebec, Canada, H3GIA6
- Novartis Investigative Site
-
-
-
-
-
Wuerzburg, Germania, 97074
- Novartis Investigative Site
-
-
-
-
California
-
Anaheim, California, Stati Uniti, 92801
- Novartis Investigative Site
-
-
Florida
-
Miramar, Florida, Stati Uniti, 33025
- Novartis Investigative Site
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Osteogenesis imperfecta
- Two or more previous fractures
- Bone mineral density Z-score of ≤ -1.0 and > -4.0
Exclusion Criteria:
- Open epiphyses
- Fracture within last 2 weeks
- Treatment with bisphosphonates/teriparatide (last 6 months)
- Surgery within last year
Other protocol-defined inclusion/exclusion criteria may apply
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Gruppo di trattamento
|
|
Nessun intervento: Untreated reference group
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Lasso di tempo: Day 1 through 141
|
The assessment of safety will be based on primarily on the frequency of adverse events, laboratory abnormalities, and serious adverse events suspected by the investigators to be related to study treatments.
The AE collection period extends from the time of first study drug administration drug until study completion.
The intensity of each AE will be characterized and classified into 1 of the 3 generic categories (mild, moderate, or severe).
The number and percentage of patients with adverse events will be tabulated by treatment group, body system and preferred term.
The periods for adverse event tabulation will be from dose administration up to next dose administration if a further dose is given, and from dose administration to EOS for the last dose administration of a patient.
|
Day 1 through 141
|
Determination of pharmacodynamic effect by means of biomarkers
Lasso di tempo: Day 1 and Day 43
|
Biomarker data from serum bone formation biomarkers: procollagen type I N-terminal propeptide, procollagen type I C-terminal propeptide, osteocalcin, and bone-specific alkaline phosphatase, and from serum bone resporption mbiomarkers: C-telopeptides of type I collagen cross-links, and N-telopeptides of type I collagen cross-links will be reported as concentration results, measured using a specific assay with a working range defined by the Lower limit of quantification and Upper limit of quantification.
It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05)
increase versus baseline in the BPS804 group on day 43.
|
Day 1 and Day 43
|
Change in Z-score from baseline to Day 141
Lasso di tempo: Day 1 and Day 141
|
Bone mineral density will be assessed by dual-energy X-ray absorptiometry of the lumbar spine.
Analysis will include four vertebral levels from L1 to L4.
Individual vertebral levels may be excluded due to artifact.
Bone mineral density Z-scores will be used as these are a comparison of a patient's BMD to that of a patient of the same age, sex, and ethnicity.
The comparison of change from baseline with the matching change in the reference group will be done by 2-sample t-tests (1-sided).
It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05)
increase versus baseline in the BPS804 group on day 141.
|
Day 1 and Day 141
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Determination of the serum concentration-time profiles of BPS804
Lasso di tempo: Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
|
Individual and overlaying individual serum concentration-time profiles of BPS804 will be constructed from the serial sampling on Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141.
In addition arithmetic and geometric mean serum concentration-time profiles of BPS804 will be constructed from the above data points.
|
Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
|
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose
Lasso di tempo: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose will be derived using using non-compartmental methods from data collected on Day 1 (4x) and Days 2, and 8.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
Determination of the maximal concentration after the first dose
Lasso di tempo: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
The maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
Determination of the time of maximal concentration after the first dose
Lasso di tempo: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
The time of maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
Determination of the maximal concentration after the second dose
Lasso di tempo: Day 15 (prior to administration and 1x after administration) and Day 16
|
The maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
|
Day 15 (prior to administration and 1x after administration) and Day 16
|
Determination of the time of maximal concentration after the second dose
Lasso di tempo: Day 15 (prior to administration and 1x after administration) and Day 16
|
The time of maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
|
Day 15 (prior to administration and 1x after administration) and Day 16
|
Determination of the area under the serum concentration-time curve from time zero to infinity after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the maximal serum concentration after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The maximal serum concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the time of maximal concentration after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The time of maximal concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the terminal elimination half-life after the third dose
Lasso di tempo: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
The terminal elimination half-life after the third dose will be derived from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141 using a compound-specific modeling approach.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
Determination of the concentration of total sclerostin in serum
Lasso di tempo: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
|
The function of sclerostin is described as an endogenous negative regulator of bone formation.
Total serum sclerostin will be measured from samples collected at screening and on days 1, 8, 15, 29, 36, 43, 57, 85, 113, and 141
|
Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
|
Immunogenicity evaluation in serum
Lasso di tempo: Days 1, 29, 85, and 141
|
Immunogenicity will only be assessed in patients randomized to the treatment group.
Anti-BPS804 antibodies will be measured in human serum on Days 1, 29, 85, and 141 An immunogenicity positive patient at end of study will be followed up until anti-BPS804 antibody levels are back to levels measured on Day 1.
|
Days 1, 29, 85, and 141
|
Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- CBPS804A2201
- 2011-001465-41 (Numero EudraCT)
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
prodotto fabbricato ed esportato dagli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su BPS804
-
Ultragenyx Pharmaceutical IncNovartis; Mereo BioPharmaRitiratoMalattia renale cronica Stadio 5D in emodialisi stabile
-
Ultragenyx Pharmaceutical IncNovartis; Mereo BioPharmaCompletato
-
Ultragenyx Pharmaceutical IncMereo BioPharmaRitiratoOsteogenesi imperfettaStati Uniti
-
Ultragenyx Pharmaceutical IncMereo BioPharmaTerminatoOsteogenesi imperfettaStati Uniti
-
Ultragenyx Pharmaceutical IncNovartis; Mereo BioPharmaCompletatoOsteoporosi | OsteopeniaStati Uniti
-
Ultragenyx Pharmaceutical IncReclutamentoOsteogenesi imperfettaStati Uniti, Canada, Germania, Francia, Polonia, Olanda, Italia, Brasile
-
Ultragenyx Pharmaceutical IncMereo BioPharmaReclutamentoOsteogenesi imperfettaStati Uniti, Canada, Tacchino, Argentina, Germania, Australia, Italia, Portogallo, Regno Unito, Polonia, Francia, Olanda
-
Ultragenyx Pharmaceutical IncMereo BioPharmaCompletatoOsteogenesi imperfetta di tipo III | Osteogenesi imperfetta tipo IV | Osteogenesi imperfetta, tipo IStati Uniti, Canada, Danimarca, Francia, Regno Unito
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletatoTumore gastricoStati Uniti