Open Label Extension Study of PREOS

NCT ID: NCT00172133

Last Updated: 2021-05-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1683 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-10-16

Study Completion Date

2005-04-13

Brief Summary

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This is an Open Label Extension Study (OLES) for patients who participated in the 18 month double-blind, placebo-controlled, Phase III trial (Protocol ALX1 11 93001 the TOP Study) studying the effect of ALX1-11, recombinant human parathyroid hormone, rhPTH(1-84), on vertebral fracture incidence. The primary objective of this study is to evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1 11 93001.

Detailed Description

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Effects of ALX1-11 on bone mineral density (BMD) have been documented in a dose-finding Phase II clinical trial in osteoporotic postmenopausal women, supplemented with calcium and Vitamin D3 but without any other treatment for osteoporosis. The anabolic effects of ALX1-11 in the lumbar vertebrae were statistically significant after the 12-month treatment period and more pronounced than any approved therapy. Additionally, animal studies have shown that the new bone formed by treatment with ALX1 11 is of good quality both histologically and biomechanically.

The primary objective of this OLES is to evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1-11-93001. A secondary objective is to assess the change in vertebral BMD and compare the changes observed in patients who received ALX1-11 or placebo in Protocol ALX1-11-93001.

Patients will receive 100 µg/day of ALX1-11 daily via subcutaneous injection in this study. Patients should continue the study drug dosing frequency they were following at the end of Protocol ALX1-11-93001.

To enhance their safety, all patients will continue to take their daily supplements of 700 mg calcium and 400 IU Vitamin D3 prior to and during this OLES. Patients whose calcium supplement was discontinued during Protocol ALX1-11-93001 should maintain that discontinuation during this OLES. However upon completion of ALX1-11 dosing in the OLES, oral calcium supplement at a dose of 700 mg each morning should be restarted and maintained for the remainder of the OLES. Additional supplemental calcium and/or Vitamin D3 will not be permitted. A daily multivitamin supplement may be taken during the study. However, the multivitamin must contain no more than 200 mg/day calcium and 400 IU/day Vitamin D3. Patients will be monitored for the development of hypercalcemia and/or hypercalciuria and managed as described in Appendices 4 and 5.

There will be a stopping rule in this OLES. Any patient who reaches a BMD T score of -0.5 or above, at the site or sites (vertebral, total hip, or femoral neck) that were used in the qualification of the patient for Protocol ALX1 11-93001, will stop ALX1-11 treatment. The patient must continue on calcium and Vitamin D3 and be followed for the remainder of this 18-month OLES. At the time of discontinuation, the patient must complete the Month 18 evaluations (Appendix 1A or 1B).

The Clinical Advisory Board (CAB) used in Protocol ALX1-11-93001 will be involved in reviewing any patient issues that arise in this OLES. This group will provide not only continuity of care for all the patients, but also enhanced and consistent safety monitoring for patients participating in the OLES.

Conditions

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Osteoporosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

All patients entering the study will receive 100mcg daily for up to 6 months, making their total exposure 24 months

Group Type EXPERIMENTAL

ALX1-11 (drug)

Intervention Type DRUG

100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen.

Interventions

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ALX1-11 (drug)

100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen.

Intervention Type DRUG

Other Intervention Names

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PREOS

Eligibility Criteria

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Inclusion Criteria

* Women who completed 18 months of treatment in Protocol ALX1-11-93001; or
* Women prematurely discontinued from Protocol ALX1-11-93001 who want to participate in OLES for the events listed below must have their clinical course reviewed and approved by the CAB for enrollment into the OLES:

* Clinical or incident lumbar vertebral fractures as assessed by the central imaging organization
* Clinical or incident hip fracture
* Confirmed bone loss at A/P lumbar vertebra or total hip or femoral neck as assessed by the central imaging organization
* Body weight below 40 kg
* Development of an exclusion criterion in Protocol ALX1-11-93001
* It must be accepted by patients whose clinical courses are reviewed by the CAB that participation in OLES may require additional tests at baseline and/or during the study to ensure their utmost safety.
* Women with the ability to self-administer a daily injection or have a designee who will give the injections;
* Women who are capable of understanding and giving written, voluntary informed consent before the start of open-label dosing with ALX1-11.

Exclusion Criteria

A. History or Concurrent Illness:

Disorders of Immunity Endocrine system Gastrointestinal system Kidney and collecting system Liver, biliary tract and pancreatic systems Musculoskeletal system

* Patients with chronic, active joint disease requiring more than one intra-articular injection every 6 months Neoplasia
* Patients who have had squamous or basal cell carcinoma of the skin may enter this study if:

1. The lesion(s) were fully resected with clear margins described in a written report by a pathologist, and
2. The patient has had no recurrence of lesions for at least one year from the time of the original resection.

Nervous system Vascular, respiratory and cardiac system \*Significant diseases or disorders are determined by history, physical exam or laboratory tests and judged by the Principal Investigator to be significant.

B. Concurrent Medication:

Patients may not use any of the following therapies while they are enrolled in this OLES without permission from the Sponsor and the PMO:
* Tetracycline antibiotics for four weeks prior to bone biopsy
* Any PTH analogs \[e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs\]
* Fluoride
* Strontium
* Phenytoin for seizure control
* Any investigational drug other than ALX1-11
* Anabolic steroids or androgens
* Active Vitamin D3 metabolites and analogs, e.g., calcitriol
* Systemic corticosteroids, more than 5 mg/day prednisone or a systemic corticosteroid formulation equivalent to 5 mg/day prednisone

1\. A patient who has been enrolled into the OLES and needs to receive an acute bolus of steroids (oral or injectable) for a self-limited illness may continue treatment in the study if the following requirements are met:
1. Exposure to steroids will be limited to no more than 30 consecutive days
2. The maximal dose of steroid (prednisone equivalent) must be limited to no more than 225 mg (7.5 mg each day for 30 days)
3. The illness is acute in nature and is not expected to recur during the remaining period of the study

* Bisphosphonates, including investigational bisphosphonates
* Calcitonin
* Estrogen replacement therapy by oral, transdermal or intramuscular administration
* SERM drugs, e.g., tamoxifen, raloxifene, Evista
* Vaginal application of estrogen-containing creams unless the dose is:

1. conjugated estrogen or estradiol: maximum of 0.5 g twice each week (total of 1.0 g weekly)
2. Estrace (Ogen): maximum of 1.0 g twice each week (total of 2.0 g weekly)
* Daily inhaled corticosteroid unless dose is equivalent to \<1200 µg/day of beclomethasone
* Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., remicade \[infliximab\]
* Methotrexate

1. The antimetabolite, methotrexate, which interferes with DNA synthesis, repair and cellular replication should not be used by patients participating in this OLES.
* In general, immunomodulatory agents with antiproliferative activity are not permitted as a concomitant medication in this OLES.
* Intra-articular injections

1\. Patients may receive a maximum of one intra-articular injection (ONE JOINT ONLY) every 6 months while participating in this OLES. The joint that is injected may be a different joint every 6 months. The dose of corticosteroid injected should not exceed the anti-inflammatory equivalent dose of Prednisone 40 mg suspension. The dose and volume should be adjusted downward as appropriate to the size of the joint.
* Provera is an acceptable concomitant medication when used according to the label instructions

Patients may be enrolled in this OLES if they have been stabilized on the following therapy for the specified amount of time:
* Thyroid Hormone (\<0.1 mg/day thyroxine) therapy for at least 6 months If taking \> 0.1 mg/day but \< 0.2 mg/day, must have serum TSH level 1. \> 0.1mU/L. Patients will be excluded if they are taking doses of \> 0.2 mg/day.

2\. However, if a patient has had a minimal change in L-thyroxine dose of \< 0.025 mg/day within 6 months of the baseline visit, and has been on this new dose for at least 2 months, the patient may be enrolled in this study. The patient's history with L-thyroxine must be clearly documented in the source documents.

3\. If a patient requires an increase in their thyroid replacement dose, as recommended by a physician who is caring for the patient, after enrollment in this OLES, the patient must have a TSH and T4 level within 3 months of the dose change to ensure the patient does not become hyperthyroid
* Stable dosage of thiazide for at least 3 consecutive months

C. Laboratory Values and Physical Examination Findings:

\- Serum calcium greater than 10.7 mg/dL (2.66 mmol/L) at baseline will be managed as outlined in Appendix 4

\- Urinary calcium to creatinine ratio greater than or equal to 1 at baseline will be managed as outlined in Appendix 5
* Elevated total serum alkaline phosphates (\> 400 U/L) at baseline will be managed as outlined in Appendix 6 except as noted for Latin and South American countries.
* Any other clinically significant abnormal value as judged by the investigator

D. Substance Abuse:

Alcohol and/or drug abuse

E. Compliance:

Suspected or confirmed poor compliance in completing clinical trial evaluations and/or clinical trial required questionnaires
Minimum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Shire

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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'The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

'Rheumatology Associates of North Alabama

Huntsville, Alabama, United States

Site Status

'Radiant Research - Phoenix North

Phoenix, Arizona, United States

Site Status

'Osteoporosis Medical Center

Beverly Hills, California, United States

Site Status

'East Bay Clinical Trial Center

Concord, California, United States

Site Status

'Loma Linda Osteoporosis Research Center

Loma Linda, California, United States

Site Status

Foundation for Osteoporosis Research

Oakland, California, United States

Site Status

'Desert Medical Advances

Palm Desert, California, United States

Site Status

'VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

'Boling Clinical Trials

Rancho Cucamonga, California, United States

Site Status

'S.D. Arthritis & Osteoporosis Medical Clinic

San Diego, California, United States

Site Status

'Radiant Research - San Diego

San Diego, California, United States

Site Status

'San Francisco General Hospital

San Francisco, California, United States

Site Status

'Longmont Medical Research Network

Longmont, Colorado, United States

Site Status

'Northeast Clinical Research, LLC

Hamden, Connecticut, United States

Site Status

'RASF - Clinical Research Center

Boca Raton, Florida, United States

Site Status

'The Center for Diabetes and Endocrine Care

Hollywood, Florida, United States

Site Status

'Florida Wellcare Alliance

Inverness, Florida, United States

Site Status

'Renstar Medical Group

Ocala, Florida, United States

Site Status

'The Arthritis Center

Palm Harbor, Florida, United States

Site Status

'The Centre for Arthritis and Rheumatic Diseases

South Miami, Florida, United States

Site Status

'Radiant Research - Stuart & LakeWorth

Stuart, Florida, United States

Site Status

'Palm Beach Research Center

West Palm Beach, Florida, United States

Site Status

'Radiant Research

Honolulu, Hawaii, United States

Site Status

'Intermountain Orthopaedics

Boise, Idaho, United States

Site Status

Rush-Prebyterian-St.Luke's Medical Center

Chicago, Illinois, United States

Site Status

'The University of Chicago

Chicago, Illinois, United States

Site Status

'University Hospital & Outpatient Center

Indianapolis, Indiana, United States

Site Status

'Mercy Arthritis and Osteoporosis Center

Des Moines, Iowa, United States

Site Status

'Wichita Clinic

Wichita, Kansas, United States

Site Status

'Ochsner Clinic

New Orleans, Louisiana, United States

Site Status

'Maine Center for Osteoporosis Research & Education

Bangor, Maine, United States

Site Status

'Bethesda Health Research Center

Bethesda, Maryland, United States

Site Status

'The Osteoporosis and Clinical Trials Center

Cumberland, Maryland, United States

Site Status

'Arthritis & Osteoporosis Center of Maryland

Frederick, Maryland, United States

Site Status

'The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Site Status

'Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

'Michigan Bone & Mineral Clinic

Detroit, Michigan, United States

Site Status

'Desoto Family Medical Center

Olive Branch, Mississippi, United States

Site Status

'St. John's Medical Research Group

Springfield, Missouri, United States

Site Status

'Arthritis, Osteoporosis Muscle Skeletal Disease Center

Concord, New Hampshire, United States

Site Status

'Anderson and Collins Clinical Research Inc.

South Plainfield, New Jersey, United States

Site Status

'New Mexico Clinical Research and Osteoporosis Center

Albuquerque, New Mexico, United States

Site Status

'Lovelace Scientific Resources

Albuquerque, New Mexico, United States

Site Status

'College of Physicians and Surgeons, Columbia University

New York, New York, United States

Site Status

'Rochester Clinical Research Inc.

Rochester, New York, United States

Site Status

'Stony Brook Clinical Research Trials Center

Stony Brook, New York, United States

Site Status

'Physicians Clinical Research Services

White Plains, New York, United States

Site Status

'Duke University Medical Center

Durham, North Carolina, United States

Site Status

'Odyssey Research Services

Bismarck, North Dakota, United States

Site Status

Michael J. Lillestol

Fargo, North Dakota, United States

Site Status

'Altru Health Systems / Altru Research Center

Grand Forks, North Dakota, United States

Site Status

'Odyssey Research Services

Minot, North Dakota, United States

Site Status

'Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

'David R. Mandel M.D. Inc.

Mayfield, Ohio, United States

Site Status

'Oklahoma Center for Arthritis Therapy & Research, Inc.

Tulsa, Oklahoma, United States

Site Status

'Osteoporosis Center

Medford, Oregon, United States

Site Status

'Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status

'Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

'University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

'Clinical Research Center of Reading LLP

West Reading, Pennsylvania, United States

Site Status

'Radiant Research

Wyomissing, Pennsylvania, United States

Site Status

'Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

'Roger Williams Medical Center

Providence, Rhode Island, United States

Site Status

'Radiant Research

Anderson, South Carolina, United States

Site Status

'Columbia Arthritis Center, PA

Columbia, South Carolina, United States

Site Status

'Radiant Research

Greer, South Carolina, United States

Site Status

'Rapid City Medical Center

Rapid City, South Dakota, United States

Site Status

'Averna Research Institute

Sioux Falls, South Dakota, United States

Site Status

'Brown Clinic

Watertown, South Dakota, United States

Site Status

'Clinsearch

Chattanooga, Tennessee, United States

Site Status

'Radiant Research/Dallas

Dallas, Texas, United States

Site Status

'Breco Research Inc.

Houston, Texas, United States

Site Status

'Diabetes Center of the Southwest

Midland, Texas, United States

Site Status

'Diabetes & Glandular Disease Research Associates, P.A.

San Antonio, Texas, United States

Site Status

'Radiant Research San Antonio

San Antonio, Texas, United States

Site Status

'Salt Lake Women's Center

Sandy City, Utah, United States

Site Status

'Fletcher Allan Health Center, UHC Campus 1

Burlington, Vermont, United States

Site Status

'Center for Arthritis and Diabetes

Newport News, Virginia, United States

Site Status

'National Clinical Research, Inc.

Richmond, Virginia, United States

Site Status

'MCV Physicians Program for Osteoporosis

Richmond, Virginia, United States

Site Status

'Osteoporosis Research Group

Seattle, Washington, United States

Site Status

'University of Wisconsin Medical Foundation

Madison, Wisconsin, United States

Site Status

'Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

'IDIM

Buenos Aires, BUE, Argentina

Site Status

'Centro Médico T.I.E.M.P.O

Buenos Aires, BUE, Argentina

Site Status

'Hospital Ramos Mejía

Buenos Aires, BUE, Argentina

Site Status

'Centro de Osteopatias Medicas

Capital Federal, CBA, Argentina

Site Status

'Universidade Federal do Paraná

Curitiba, Paraná, Brazil

Site Status

'Hospital Santa Casa de Misericórdia do Rio de Janeiro

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

'Hospital do Servidor Público do Rio de Janeiro

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

'Universidade Federal de São Paulo

São Paulo, São Paulo, Brazil

Site Status

'Instituto de Saúde e Bem Estar da Mulher

São Paulo, São Paulo, Brazil

Site Status

'Hospital Heliópolis

São Paulo, São Paulo, Brazil

Site Status

'Heritage Medical Research Clinic

Calgary, Alberta, Canada

Site Status

Osteoporosis Research Center

Vancouver, British Columbia, Canada

Site Status

'Manitoba Clinic

Winnipeg, Manitoba, Canada

Site Status

Charlton medical Centre

Hamilton, Ontario, Canada

Site Status

Rafat Faraawi

Kitchener, Ontario, Canada

Site Status

'Centre for Activity and Aging

London, Ontario, Canada

Site Status

St. Joseph's Health Centre

London, Ontario, Canada

Site Status

'Royal Victoria Hospital

Montreal, Ontario, Canada

Site Status

Oakville Bone Center

Oakville, Ontario, Canada

Site Status

Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

'Sunnybrook and Women's College Health Science Center

Toronto, Ontario, Canada

Site Status

'St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

'Osteoporosis Research Program

Toronto, Ontario, Canada

Site Status

Jude F. Rodrigues

Windsor, Ontario, Canada

Site Status

'Riverside Medical Centre

Charlottetown, Prince Edward Island, Canada

Site Status

'Complexe Hospitalier de la Sagami

Chicoutimi, Quebec, Canada

Site Status

'Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

'Centre de Recherche du CHUM - Hopital Saint-Luc

Montreal, Quebec, Canada

Site Status

Centre de recherche - CORQ

Sainte-Foy, Quebec, Canada

Site Status

Novabyss Research Clinic

Sherbrooke, Quebec, Canada

Site Status

'Saskatoon Osteoporosis Centre

Saskatoon, Saskatchewan, Canada

Site Status

'Soroka Medical Center

Beersheba, , Israel

Site Status

'Rambam Medical Center

Haifa, , Israel

Site Status

'Lin Medical Center

Haifa, , Israel

Site Status

'Hadassah University Hospital

Jerusalem, , Israel

Site Status

'Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

'Lis Maternity Hospital

Tel Aviv, , Israel

Site Status

'Hospital Angeles de las Lomas

Huixquilucan, EMEX, Mexico

Site Status

'Hospital Aranda de la Parra

León, Guanajuato, Mexico

Site Status

'OPD Hospital Civil de Guadalajara Dr. Juan I. Menchaca

Guadalajara, Jalisco, Mexico

Site Status

'Hospital Civil de Belem

Guadalajara, Jalisco, Mexico

Site Status

'Medica Monraz

Guadalajara, Jalisco, Mexico

Site Status

'Instituto Mexicano de Investigacion Clinica

Mexico City, Mexico City, Mexico

Site Status

'Hospital de Mexico

Mexico City, Mexico City, Mexico

Site Status

'Hospital Universitario de Monterrey

Monterrey Nuevo Leon, , Mexico

Site Status

'Spitalul Clinic Judetean Cluj-Napoca

Cluj-Napoca, , Romania

Site Status

'Scientific Center of Endocrinology of RAMS

Moscow, , Russia

Site Status

'Russian Academy for Advanced Medical Studies

Moscow, , Russia

Site Status

Countries

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United States Argentina Brazil Canada Israel Mexico Romania Russia

Other Identifiers

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CL1-11-002

Identifier Type: -

Identifier Source: org_study_id

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