ACTHAR for Acute Treatment of Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01984268
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 26.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Adenocorticotrophic Hormone provides safe and effective treatment to induce disease remission in rheumatoid arthritis patients with active disease due to an inadequate response to methotrexate.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: ACTHAR	Phase 2

Detailed Description

The standard treatment for rheumatoid arthritis is using disease-modifying anti-rheumatic drugs such as methotrexate to control joint pain and swelling. Often times rheumatoid arthritis patients experience inadequate response to methotrexate with acute or persistent joint pain and swelling. In these patients, alternative or additional immunosuppressive therapy is needed to induce disease remission. In the present clinical trial, ACTHAR is being studied to induce disease remission on rheumatoid arthritis patients who have inadequate response to methotrexate therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Adenocorticotrophic Hormone for Acute Treatment of Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
• Study Start Date: Jun 23, 2014
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Four week ACTHAR treatment Rheumatoid arthritis subjects with inadequate response to methotrexate will be randomized to receive twice a week dosing of ACTHAR for a period of four weeks.	Drug: ACTHAR; Other Names: Corticotropin
Experimental: Twelve week ACTHAR treatment Rheumatoid arthritis subjects with inadequate response to methotrexate will be randomized to receive twice a week dosing of ACTHAR for a period of twelve weeks.	Drug: ACTHAR; Other Names: Corticotropin

Outcome Measures

Primary Outcome Measures

1. Improvement in Disease Activity as Measured by ACR20 and ACR50. [36 weeks]

Secondary Outcome Measures

1. Adverse Events [36 weeks]

Other Outcome Measures

1. Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) [36 weeks]

2. Change From Baseline in the Short Form-36 (SF-36) Item Questionnaire Physical Component Summary (PCS) [36 weeks]

3. Change From Baseline in the Short Form-36 (SF-36) Item Questionnaire Mental Component Summary (MCS) [36 weeks]

4. Change From Baseline in Patient's Assessment of Arthritis Pain - Visual Analog Scale (VAS) [36 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female at least 18 years of age at the time of screening

• Subject is diagnosed with RA no less than 6 months prior to the screening

• Subject meets the 2010 ACR/EULAR Classification Criteria for RA (Arthritis Rheum 2010:62;2569-2581) with a score of ≥6

• Subject is seropositive for RF and/or anti-CCP antibodies as part of the diagnostic criteria for RA

• Subject has moderately to severely active RA during screening, as defined by a DAS28-ESR > 3.2

• Subject has moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints

• Subject has had an inadequate response to the continuous use of methotrexate for at least 12 weeks prior to study entry with a nonchanging dose for at least 8 weeks prior to study entry

Exclusion Criteria:

• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening

• Treatment with any biological agents within 4 weeks (or 5 half-lives of the agent, whichever is longer) of screening

• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline

• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including Cushing's disease or uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)

• Current liver disease as determined by principal investigator unless related to primary disease under investigation

• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds)

• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening

• Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating treatment. Patients treated for tuberculosis with no recurrence in 3 years are permitted.

• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years unless related to primary disease under investigation

• Pregnant women or nursing (breast feeding) mothers

• Patients with reproductive potential not willing to use an effective method of contraception.

• History of alcohol, drug or chemical abuse within 1 year prior to screening.

• Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.

• Body weight of > 150 kg

• Serum creatinine > 1.6 mg/dL (141 µmol/L) in female subjects and > 1.9 mg/dL (168 µmol/L) in male subjects. Subjects with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are >30

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)

• Total Bilirubin > ULN

• Platelet count < 100 x 109/L (100,000/mm3)

• Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)

• White Blood Cells < 3.0 x 109/L (3000/mm3)

• Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)

• Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)

• Positive Hepatitis BsAg or Hepatitis C antibody

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization

• A diagnosis of any of the followings: scleroderma, osteoporosis, infection throughout the body, ocular herpes simplex, history of or a current stomach ulcer, uncontrolled hypertension (systolic blood pressure greater than 160), or allergy to pig-derived proteins

• Subject does not tolerate methotrexate and/or NSAID due to side effects or toxicities

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center
• Mallinckrodt

Investigators

• Principal Investigator: Richard C Chou, MD PhD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT01984268
• Other Study ID Numbers: D13146
• First Posted: Nov 14, 2013
• Last Update Posted: Jan 15, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Dartmouth-Hitchcock Medical Center: Rheumatoid arthritis; ACTHAR; Methotrexate; Inadequate response
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adrenocorticotropic Hormone

Study Results

Participant Flow

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Period Title: Overall Study
STARTED	15
COMPLETED	0
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Overall Participants	15
Age, Customized (Count of Participants)
>18	15 100%
Sex: Female, Male (Count of Participants)
Female	9 60%
Male	6 40%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	15 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Improvement in Disease Activity as Measured by ACR20 and ACR50.
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

2. Secondary Outcome

Title	Adverse Events
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

3. Other Pre-specified Outcome

Title	Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

4. Other Pre-specified Outcome

Title	Change From Baseline in the Short Form-36 (SF-36) Item Questionnaire Physical Component Summary (PCS)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

5. Other Pre-specified Outcome

Title	Change From Baseline in the Short Form-36 (SF-36) Item Questionnaire Mental Component Summary (MCS)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

6. Other Pre-specified Outcome

Title	Change From Baseline in Patient's Assessment of Arthritis Pain - Visual Analog Scale (VAS)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.

Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Measure Participants	0

Adverse Events

Time Frame	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Adverse Event Reporting Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
Arm/Group Title	Entire Study
Arm/Group Description	The study was placed on voluntary hold prior to completion by the PI. The voluntary hold stayed in place until the study's IRB approval expired. The study was subsequently closed by the IRB. The PI no longer has access to any data, and the PI has left the institution. No reportable study outcome data is available as determined by the IRB.
All Cause Mortality
	Entire Study
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Entire Study
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Entire Study
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.