Open Label Extension Study of PREOS

Osteoporosis Clinical Trial

— OLES  

Official title:

An 18-Month Open Label Extension Study (OLES) of the Safety and Efficacy of Recombinant Human Parathyroid Hormone, rhPTH(1-84), ALX1-11, in Women With Postmenopausal Osteoporosis Who Participated in Protocol ALX1-11-93001 (TOP Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00172133
• Other study ID #: CL1-11-002
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2001
• Est. completion date: April 13, 2005

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1683
• Est. completion date: April 13, 2005
• Est. primary completion date: April 13, 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• ALX1-11 (drug)
100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen.

Locations

Country	Name	City	State
Argentina	'Centro Médico T.I.E.M.P.O	Buenos Aires	BUE
Argentina	'Hospital Ramos Mejía	Buenos Aires	BUE
Argentina	'IDIM	Buenos Aires	BUE
Argentina	'Centro de Osteopatias Medicas	Capital Federal	CBA
Brazil	'Hospital Santa Casa de Misericórdia do Rio de Janeiro	'Rio de Janeiro	RJ
Brazil	'Universidade Federal do Paraná	Curitiba	PR
Brazil	'Hospital do Servidor Público do Rio de Janeiro	Rio de Janeiro	RJ
Brazil	'Hospital Heliópolis	Sao Paulo	SP
Brazil	'Instituto de Saúde e Bem Estar da Mulher	Sao Paulo	SP
Brazil	'Universidade Federal de São Paulo	Sao Paulo	SP
Canada	'Saskatoon Osteoporosis Centre	'Saskatoon	Saskatchewan
Canada	'Heritage Medical Research Clinic	Calgary	Alberta
Canada	'Riverside Medical Centre	Charlottetown	Prince Edward Island
Canada	'Complexe Hospitalier de la Sagami	Chicoutimi	Quebec
Canada	Charlton medical Centre	Hamilton	Ontario
Canada	Rafat Faraawi	Kitchener	Ontario
Canada	'Centre for Activity and Aging	London	Ontario
Canada	St. Joseph's Health Centre	London	Ontario
Canada	'Centre de Recherche du CHUM - Hopital Saint-Luc	Montreal	Quebec
Canada	'Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	'Royal Victoria Hospital	Montreal	Ontario
Canada	Oakville Bone Center	Oakville	Ontario
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Centre de recherche - CORQ	Sainte-Foy	Quebec
Canada	Novabyss Research Clinic	Sherbrooke	Quebec
Canada	'Osteoporosis Research Program	Toronto	Ontario
Canada	'St. Michael's Hospital	Toronto	Ontario
Canada	'Sunnybrook and Women's College Health Science Center	Toronto	Ontario
Canada	Osteoporosis Research Center	Vancouver	British Columbia
Canada	Jude F. Rodrigues	Windsor	Ontario
Canada	'Manitoba Clinic	Winnipeg	Manitoba
Israel	'Soroka Medical Center	Beer Sheva
Israel	'Lin Medical Center	Haifa
Israel	'Rambam Medical Center	Haifa
Israel	'Hadassah University Hospital	Jerusalem
Israel	'Chaim Sheba Medical Center	Ramat Gan
Israel	'Lis Maternity Hospital	Tel Aviv
Mexico	'Hospital Angeles de las Lomas	'Huixquilucan	Emex
Mexico	'Hospital Civil de Belem	Guadalajara	JAL
Mexico	'Medica Monraz	Guadalajara	JAL
Mexico	'OPD Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	JAL
Mexico	'Hospital Aranda de la Parra	Leon	GTO
Mexico	'Hospital de Mexico	Mexico	DF
Mexico	'Instituto Mexicano de Investigacion Clinica	Mexico	DF
Mexico	'Hospital Universitario de Monterrey	Monterrey Nuevo Leon
Romania	'Spitalul Clinic Judetean Cluj-Napoca	Cluj-Napoca
Russian Federation	'Russian Academy for Advanced Medical Studies	Moscow
Russian Federation	'Scientific Center of Endocrinology of RAMS	Moscow
United States	'Lovelace Scientific Resources	Albuquerque	New Mexico
United States	'New Mexico Clinical Research and Osteoporosis Center	Albuquerque	New Mexico
United States	'Radiant Research	Anderson	South Carolina
United States	'Maine Center for Osteoporosis Research & Education	Bangor	Maine
United States	'Bethesda Health Research Center	Bethesda	Maryland
United States	'Osteoporosis Medical Center	Beverly Hills	California
United States	'The University of Alabama at Birmingham	Birmingham	Alabama
United States	'Odyssey Research Services	Bismarck	North Dakota
United States	'RASF - Clinical Research Center	Boca Raton	Florida
United States	'Intermountain Orthopaedics	Boise	Idaho
United States	'Brigham & Women's Hospital	Boston	Massachusetts
United States	'Fletcher Allan Health Center, UHC Campus 1	Burlington	Vermont
United States	'Clinsearch	Chattanooga	Tennessee
United States	'The University of Chicago	Chicago	Illinois
United States	Rush-Prebyterian-St.Luke's Medical Center	Chicago	Illinois
United States	'Cleveland Clinic Foundation	Cleveland	Ohio
United States	'Columbia Arthritis Center, PA	Columbia	South Carolina
United States	'Arthritis, Osteoporosis Muscle Skeletal Disease Center	Concord	New Hampshire
United States	'East Bay Clinical Trial Center	Concord	California
United States	'The Osteoporosis and Clinical Trials Center	Cumberland	Maryland
United States	'Radiant Research/Dallas	Dallas	Texas
United States	'Mercy Arthritis and Osteoporosis Center	Des Moines	Iowa
United States	'Michigan Bone & Mineral Clinic	Detroit	Michigan
United States	'Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	'Duke University Medical Center	Durham	North Carolina
United States	Michael J. Lillestol	Fargo	North Dakota
United States	'Arthritis & Osteoporosis Center of Maryland	Frederick	Maryland
United States	'Altru Health Systems / Altru Research Center	Grand Forks	North Dakota
United States	'Radiant Research	Greer	South Carolina
United States	'Northeast Clinical Research, LLC	Hamden	Connecticut
United States	'The Center for Diabetes and Endocrine Care	Hollywood	Florida
United States	'Radiant Research	Honolulu	Hawaii
United States	'Breco Research Inc.	Houston	Texas
United States	'Rheumatology Associates of North Alabama	Huntsville	Alabama
United States	'University Hospital & Outpatient Center	Indianapolis	Indiana
United States	'Florida Wellcare Alliance	Inverness	Florida
United States	'Loma Linda Osteoporosis Research Center	Loma Linda	California
United States	'Longmont Medical Research Network	Longmont	Colorado
United States	'University of Wisconsin Medical Foundation	Madison	Wisconsin
United States	'David R. Mandel M.D. Inc.	Mayfield	Ohio
United States	'Osteoporosis Center	Medford	Oregon
United States	'Diabetes Center of the Southwest	Midland	Texas
United States	'Medical College of Wisconsin	Milwaukee	Wisconsin
United States	'Odyssey Research Services	Minot	North Dakota
United States	'Ochsner Clinic	New Orleans	Louisiana
United States	'College of Physicians and Surgeons, Columbia University	New York	New York
United States	'Center for Arthritis and Diabetes	Newport News	Virginia
United States	Foundation for Osteoporosis Research	Oakland	California
United States	'Renstar Medical Group	Ocala	Florida
United States	'Desoto Family Medical Center	Olive Branch	Mississippi
United States	'Desert Medical Advances	Palm Desert	California
United States	'The Arthritis Center	Palm Harbor	Florida
United States	'VA Palo Alto Health Care System	Palo Alto	California
United States	'Thomas Jefferson University	Philadelphia	Pennsylvania
United States	'Radiant Research - Phoenix North	Phoenix	Arizona
United States	'University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	'Rhode Island Hospital	Providence	Rhode Island
United States	'Roger Williams Medical Center	Providence	Rhode Island
United States	'Boling Clinical Trials	Rancho Cucamonga	California
United States	'Rapid City Medical Center	Rapid City	South Dakota
United States	'MCV Physicians Program for Osteoporosis	Richmond	Virginia
United States	'National Clinical Research, Inc.	Richmond	Virginia
United States	'Rochester Clinical Research Inc.	Rochester	New York
United States	'Diabetes & Glandular Disease Research Associates, P.A.	San Antonio	Texas
United States	'Radiant Research San Antonio	San Antonio	Texas
United States	'Radiant Research - San Diego	San Diego	California
United States	'S.D. Arthritis & Osteoporosis Medical Clinic	San Diego	California
United States	'San Francisco General Hospital	San Francisco	California
United States	'Salt Lake Women's Center	Sandy	Utah
United States	'Osteoporosis Research Group	Seattle	Washington
United States	'Averna Research Institute	Sioux Falls	South Dakota
United States	'The Centre for Arthritis and Rheumatic Diseases	South Miami	Florida
United States	'Anderson and Collins Clinical Research Inc.	South Plainfield	New Jersey
United States	'St. John's Medical Research Group	Springfield	Missouri
United States	'Stony Brook Clinical Research Trials Center	Stony Brook	New York
United States	'Radiant Research - Stuart & LakeWorth	Stuart	Florida
United States	'Oklahoma Center for Arthritis Therapy & Research, Inc.	Tulsa	Oklahoma
United States	'Brown Clinic	Watertown	South Dakota
United States	'Palm Beach Research Center	West Palm Beach	Florida
United States	'Clinical Research Center of Reading LLP	West Reading	Pennsylvania
United States	'The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	'Physicians Clinical Research Services	White Plains	New York
United States	'Wichita Clinic	Wichita	Kansas
United States	'Radiant Research	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Israel,  Mexico,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (TOP).		24 months of treatment
Secondary	To evaluate the continued efficacy of once-daily treatment with ALX1-11 for maintaining increases in BMD and other measures of bone quality and strength.		24 months of treatment