TRES: Open Label Extension

Sponsor

Shire (Industry)

Overall Status

Completed

CT.gov ID

NCT00172120

Collaborator

(none)

Enrollment

Locations

21.5

Actual Duration (Months)

7.6

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

TRES will evaluate the effects of continued ALX1-11 treatment on the safety and efficacy variables assessed in the OLE study for a maximum treatment duration of 36 months in OLES and TRES combined.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: ALX1-11	Phase 3

Detailed Description

The primary goal of osteoporosis therapy is to prevent fracture, and anabolic agents can accomplish this by strengthening bone structure, which is accompanied by changes in BMD. Effects of ALX1-11 on BMD have been previously documented in a dose-finding Phase II clinical trial in osteoporotic postmenopausal women taking calcium and vitamin D supplements, who were otherwise naive to osteoporosis therapies. The anabolic effects of ALX1-11 on lumbar vertebrae were statistically significant compared to placebo after 12 months of treatment. In addition, animal studies showed that the new bone formed by treatment with ALX1 11 is of good quality both histologically and biomechanically (Mosekilde et al., 1991; Kimmel et al., 1993).

Protocol ALX1-11-93001 (TOP) assessed the effect of 18 months of ALX1-11 treatment on fracture incidence as a primary efficacy variable, and Protocol CL1-11-002 (OLES) assessed the effect on BMD for up to 24 months of treatment. Subjects who will be enrolled in the current study (TRES) will be those who received placebo in TOP and ALX1-11 in OLES. TRES will evaluate the effects of continued ALX1-11 treatment on the safety and efficacy variables assessed in the OLE study for a maximum treatment duration of 36 months in the OLES and TRES combined.

Study Design

Study Type:

Interventional

Actual Enrollment :

91 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An 18-month, Open-label Extension Study of Once-daily ALX1-11 for the Treatment of Postmenopausal Women With Osteoporosis (TRES)

Actual Study Start Date :

Jan 10, 2005

Actual Primary Completion Date :

Oct 27, 2006

Actual Study Completion Date :

Oct 27, 2006

Outcome Measures

Primary Outcome Measures

The primary objective of this study is to evaluate the safety of continued once-daily dosing with 100 mg ALX1-11 in postmenopausal osteoporotic women who participated in TOP and OLES clinical trials. [Throughout the study period of approximately 18 months.]

Secondary Outcome Measures

The secondary objective is to evaluate the continued efficacy of once-daily treatment with ALX1-11 for maintaining increases in bone mineral density (BMD). [Throughout the study period of approximately 18 months.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Received placebo in TOP
Completed 18 months of daily treatment with ALX1-11 in OLES
Received their last dose of ALX1-11 in OLES within 3 months (90 days) of dosing in this study
Have the ability to continue to self-administer, or have a designee administer, a daily injection
Have the ability to understand, and willingness to sign, an informed consent form (ICF)

Exclusion Criteria:

Subjects are excluded who have developed any of the exclusion criteria for OLES, or modifications as listed below.

Concurrent Diseases Subjects are excluded if they have developed any of the diseases or illnesses listed since enrollment in OLES.

Immune.Significant* immunological disorders; including AIDSAllergies to ALX1-11 or its constituents
Endocrine.Significant* endocrine disorders, including hyper or hypoparathyroidism, Cushing's disease, hyperthyroidism
Gastrointestinal (GI).Significant* GI disorders
Kidney and Collecting.Significant* renal disorders or impaired renal function, nephrolithiasis or urolithiasis, verified kidney calcification, etc.
Liver, biliary tract, pancreatic.Significant* hepatic or pancreatic disorders, active hepatitis, or pancreatitis
Musculoskeletal.Metabolic bone disease, eg., Paget's disease, osteogenesis imperfecta, or osteomalacia -Chronic, active joint disease and/or joint infection
Neoplasia.Cancer, with the exception of squamous or basal cell carcinoma**
Nervous.Significant* neurological or psychiatric disease
Vascular, respiratory, and cardiac.Significant* unstable cardiac or pulmonary disease

(*)Significance will be determined by the investigator on the basis of history, physical exam, and/or laboratory screens. Significant disorders necessitate ongoing changes in therapeutic medication or frequent monitoring.

(**)Subjects who have had either squamous or basal cell carcinoma of the skin can enroll if: 1. The lesion(s) was fully resected with clear margins described in a written report by a pathologist, AND 2. The subject has had no recurrence of lesions for at least 1 year from the time of the original resection

Prohibited Concomitant Medications

PTH analogs*
Fluoride
Strontium
Calcitonin
Vitamin D metabolites or analogs(eg., calcitriol)
Immunomodulatory agents with antiproliferative activity
Cytostatics**
Thyroxine. Prohibited if dose > 0.2 mg/day (see Table 4-4 for allowed conditions)
Bisphosphonate
Anabolic steroids or androgens

(*)PTH (parathyroid hormone) analogs include PTH(1-34), PTHrP, and other analogs

(**)eg, azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., infliximab [Remicade™])

Medications Requiring a Washout Period - Subjects who completed OLES and then began taking medications listed in the following table may enroll in this study after a washout period of 30 days.

Hormone-replacement therapy*
Methotrexate
SERMs**
Any investigational drug
Other medications known to affect the metabolism of bone
30 days with PMO approval

(*)Includes estrogen- and estrogen/progesterone-replacement therapy given by oral, transdermal, or intramuscular administration b SERMs (selective estrogen receptor modulator) include tamoxifen and raloxifene (Evista®) PMO = project medical officer

(**)SERMs (selective estrogen receptor modulator) include tamoxifen and raloxifene (Evista®) PMO = project medical officer

Medications Allowed if Specific Conditions Are Met-Medications that are allowed under specific conditions are listed:

Thyroid hormone. At a stable dose <= 0.2 mg/day
Thiazide. At a stable dose
Vaginal application of estrogen-containing creams. Conjugated estrogen or estradiol at a dose of <=0.5 g administered twice each week (total of 1.0 g weekly). Estrace® (Ogen)at a dose <=1.0 g twice each week (total of 2.0 g weekly)
Systemic corticosteroids. Acute bolus of steroids (oral or injectable) for a self-limited illness allowed under the following conditions: 1. Exposure to steroids limited to £30 consecutive days 2. Maximal dose (prednisone-equivalent) does not exceed 225 mg (5 mg/day for 30 days) 3. Illness was acute in nature and not expected to recur during the remaining treatment period of the study
Inhaled corticosteroids. At a dose <1200 mg/day beclomethasone equivalent
Intra-articular injections. A single intra-articular injection allowed every 6 months if the dose of corticosteroid injected is less than an equivalent dose of prednisone 40 mg suspension
Phenytoin. No phenytoin exposure allowed within 5 years of Month 0 of TOP. Allowed if last phenytoin exposure was >15 years prior to screening for TOP or was between 5-15 years before screening for TOP and for <2 months duration
Provera® (medroxyprogesterone). Allowed if used according to the label

Laboratory Values and Physical Examination Findings - For excluded laboratory values, the levels shown in the following table are the upper limits for exclusions based on specific test results, with the exception of calculated creatinine clearance and serum 25(OH) vitamin D, for which the limits are lower. All exclusionary laboratory results should be confirmed by a repeat test. Subjects may be excluded for any other clinically abnormal value, as determined by the investigator.

Fasting serum total calcium (Ca). Subject excluded if value* >10.2 mg/dL**,***
24-hour urinary Ca. Subject excluded if value* >360 mg/day**
Serum total alkaline phosphatase. Subject excluded if value* 3X upper limit of normal for laboratory
Serum PTH***. Subject excluded if value* >50 pg/mL
Calculated creatinine clearance*** Subject excluded if value* <50 mL/minute
Serum 25(OH) vitamin D***. Subject excluded if value* <20 ng/mL

(*)Exclude subject only if repeat assessment confirms the result.

(**)Not to be used as a reason for premature discontinuation during the study. Subjects with elevated values after enrollment are to be managed by the appropriate algorithm (Appendices 2 and 3).

(***)Not an exclusion criterion in OLES

Substance Abuse-Subjects are excluded for a history of alcohol and/or drug abuse as determined by the investigator.

Compliance-Subjects may be excluded for suspected or confirmed poor compliance in completing clinical trial evaluations and/or questionnaires.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	'Osteoporosis Medical Center	Beverly Hills	California	United States	90211
2	'The University of Chicago	Chicago	Illinois	United States	60637
3	'Michigan Bone & Mineral Clinic	Detroit	Michigan	United States	48236
4	'Odyssey Research Services	Bismarck	North Dakota	United States	58501
5	Michael J. Lillestol	Fargo	North Dakota	United States	58103
6	'Odyssey Research Services	Minot	North Dakota	United States	58701
7	'Rapid City Medical Center	Rapid City	South Dakota	United States	57701
8	'Brown Clinic	Watertown	South Dakota	United States	57201
9	'Fletcher Allan Health Center, UHC Campus 1	Burlington	Vermont	United States	05401
10	'IDIM	Buenos Aires	BUE	Argentina	C1012AAR
11	'Centro Médico T.I.E.M.P.O	Buenos Aires	BUE	Argentina	C1117ABH
12	'Centro de Osteopatias Medicas	Capital Federal	CBA	Argentina	C1114AAI