Study in Patients With Untreated Multiple Myeloma and Renal Insufficiency

Study Overview
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Brief Summary
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The study will evaluate the effects of BHQ880 in patients with previously untreated multiple myeloma and renal insufficiency who are not considered candidates for bisphosphonate therapy. The primary objective of the study will be to evaluate the effect of BHQ880 in combination with bortezomib and dexamethasone, compared to placebo administered with the combination on the time to first Skeletal Related Event (SRE) on study.

Official Title
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A Double-blind, Placebo-controlled, Randomized Phase 2 Study of BHQ880, an Anti-Dickkopf1 (DKK1) Monoclonal Antibody (mAb), in Patients With Untreated Multiple Myeloma and Renal Insufficiency

Conditions
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Multiple Myeloma, Renal Insufficiency

Intervention / Treatment
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* Drug: BHQ880
* Drug: BHQ880 Placebo
* Drug: bortezomib
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of multiple myeloma Life expectancy of more than 6 months in the absence of intervention Must not have received previous or be receiving current antimyeloma therapies Renal insufficiency Recovered from the effects of any prior surgery or radiotherapy Exclusion Criteria: Prior IV bisphosphonate therapy at any time or oral bisphosphonate therapy within 4 months of study entry Paget's disease of bone or uncorrected hyperparathyroidism Impaired cardiac function Known HIV, known active hepatitis B, or known or suspected hepatitis C infection Pregnant or nursing (lactating) women, Women of child-bearing potential, UNLESS agreeable to using 2 birth control methods Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BHQ880 + bortezomib and dexamethasone<br> | Drug: BHQ880<br> <br> Drug: bortezomib<br>* intravenous injection<br>Drug: dexamethasone<br>* Oral<br>|
| Placebo Comparator: BHQ880 Placebo + bortezomib and dexamethasone<br> | Drug: BHQ880 Placebo<br>* Intravenous infusion<br>Drug: bortezomib<br>* intravenous injection<br>Drug: dexamethasone<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of BHQ880 compared with placebo on time to first Skeletal Related Event (SRE) in patients with untreated multiple myeloma and renal insufficiency in combination with bortezomib and dexamethasone | Time to first SRE from randomization | 18-month median time to first SRE assumed for the placebo arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of BHQ880 in combination with bortezomib and dexamethasone | Number of patients with adverse events/serious adverse events, abnormal clinical laboratory values, and the assessment of immunogenicity | From screening through month 17 | 
| Characterize the PharmacoKinetics (PK) profiles of BHQ880 and bortezomib | Determine the pharmacokinetic parameters for BHQ880 and bortezomib (Cmax, Tmax, AUC0-tlast, t1/2, and accumulation ratio of BHQ880). | At screening and weeks 1, 2, 4, 7, 10, 11, 13, 16, 25 and 34 | 
| Evaluate the effect of BHQ880 on bone metabolism | 1) Change in bone mineral density, measured by dual-emission X-ray absorptiometry (DXA), from randomization to 12 and 18 months; 2) Change in bone strength, measured by quantitative computed tomography (qCT), from randomization to 3 and 6 months | At screening and at months 3, 6, 12, and 18 | 
| Determine the antimyeloma effect of BHQ880 compared to placebo when used in combination with bortezomib and dexamethasone. | 1) The overall response rate (partial response plus complete response); 2) Progression-free survival following initiation of BHQ880 | From the first dose of study medication through month 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma, renal insufficiency, untreated multiple myeloma