Protocol CNTO148JIA3003 GO-VIVA

Principal Investigator: Christi Joy Inman
Keywords: Arthritis Department: Pediatric Administration
IRB Number: 00082306 Co Investigator:  
Specialty: Pediatrics, General, Pediatrics, General
Sub Specialties: Adolescent Medicine,
Recruitment Status: Recruiting

Contact Information

Julianna Dorsch
Julianna.Dorsch@hsc.utah.edu
801-587-5200

Brief Summary

The primary objective of this study is to assess the pharmacokinetics (PK) of intravenously administered golimumab in subjects (ages 2 to less than 18 years) with polyarticular JIA (pJIA) manifested by ≥5 joints with active arthritis despite methotrexate (MTX) therapy for ≥3 months.

The secondary objectives of this study are to evaluate IV golimumab in subjects with pJIA with respect to efficacy (relief of signs and symptoms, physical function, quality of life), safety (AEs, SAEs, and assessment of laboratory parameters), and immunogenicity (antibodies to golimumab).

Inclusion Criteria

1. Subjects must be age 2 years to less than 18 years with a body weight >15 kg at the time of screening and at Week 0.

2. Diagnosis must be made per JIA ILAR diagnostic criteria and the onset of disease must have been before the subject’s 16th birthday.

3. Active JIA of one of the following subtypes:

a. Rheumatoid factor positive or negative pJIA for ≥3 months prior to screening, or

b. Systemic JIA with no systemic symptoms for ≥3 months, but with polyarthritis for ≥3 months prior to screening,

OR

c. Extended oligoarticular JIA ≥3 months prior to screening, or

d. Polyarticular juvenile psoriatic arthritis ≥3 months prior to screening, or,

e. Enthesitis related arthritis ≥3 months prior to screening.

4. Failure or inadequate response to at least a 3 month course of MTX before screening.

5. Subjects must have ≥5 joints with active arthritis at screening and at Week 0 as defined
by ACR criteria (ie, a joint with either swelling, or in the absence of swelling, limited
range of motion associated with pain on motion or tenderness).

6. Subjects must have a screening CRP of ≥0.1 mg/dL.

7. Subjects must have active pJIA despite current use of oral, intramuscular, or
subcutaneous MTX for ≥2 months before screening. For subjects with BSA <1.67 m2,
the MTX dose must be between 10 to 30 mg/m2 per week and stable for ≥4 weeks before
screening. For subjects with BSA ≥1.67 m2, the MTX dose must be a minimum of
15 mg/week and must be stable for ≥4 weeks before screening. In situations where there
is documented intolerance of doses >10 mg/m2 weekly (for subjects with BSA
<1.67 m2) or ≥15 mg/week (for subjects with BSA ≥1.67 m2); or where documented
country or site regulations prohibit use of ≥15 mg of MTX per week in subjects with
BSA ≥1.67 m2, subjects may be entered into the trial on a lower dose of MTX.

8. If using corticosteroids, must be on a stable dose of ≤10 mg/day prednisone equivalent or 0.20 mg/kg/day (whichever is lower) for ≥2 weeks before first administration of study agent If currently not using corticosteroids, the subject must have not received corticosteroids for at least 2 weeks before the first dose administration. Subjects with systemic onset JIA but without systemic symptoms must be on a stable dose of corticosteroids for at least 3 days prior to screening.

9. If using NSAIDs, must be on a stable dose for ≥2 weeks before screening. If not currently using NSAIDs, must not have taken them for at least 2 weeks before screening.

10. Subjects are considered eligible according to the following TB screening criteria:

a. Have no history of latent or active TB prior to screening. An exception is made for subjects currently receiving treatment for latent TB with no evidence of active TB, or who have a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous anti-tuberculousis treatment and provide appropriate documentation.

b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.

c. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to the first administration of study agent.

d. Within 6 weeks prior to the first administration of study agent, have a negative QuantiFERON®-TB Gold (Attachment 1) test result, or have a newly identified positive QuantiFERON®-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB (Section 9.1.2) has been initiated prior to the first administration of study agent. Within 6 weeks prior to the first administration of study agent, a negative tuberculin skin test (Attachment 2), or a newly identified positive tuberculin skin test in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated prior to the first administration of study agent, is additionally required if the QuantiFERON®-TB Gold test is not approved/registered in that country or the tuberculin skin test is mandated by local health authorities.

e. Indeterminate results should be handled as outlined in Section 9.1.2. Subjects with persistently indeterminate QuantiFERON®-TB Gold test results may be enrolled without treatment for latent TB, if active TB is ruled out, and the subject has no additional risk factors for TB as determined by the investigator. This determination must be promptly reported to the Sponsor’s medical monitor and recorded in the subject's source documents and initialed by the investigator.

f. The QuantiFERON®-TB Gold test and the tuberculin skin test are not required at screening for subjects with a history of latent TB and ongoing treatment for latent TB or documentation of having completed adequate treatment as described above; Subjects with documentation of having completed adequate treatment as described above are not required to initiate additional treatment for latent TB.

g. Unless country or site guidelines do not recommend a chest radiograph as a necessary screening process prior to initiation of anti-TNFα therapies, a chest radiograph (posterior-anterior view) must have been taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.

11. Subjects must be medically stable on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population.

12. Girls must be either:

1.  Not of childbearing potential: premenarchal; permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy,

OR

2.  Of childbearing potential, and if sexually active, practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject and at the discretion of the investigator/per local regulations). Girls of childbearing potential must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study drug.

Note: If the childbearing potential changes after start of the study (eg, girl who is not heterosexually active becomes active, premenarchal girl experiences menarche) a girl must begin a highly effective method of birth control, as described above.

13. Girls of childbearing potential must have a negative serum (-human chorionic gonadotropin [-hCG]) test at screening, and a negative urine pregnancy test at each study visit where golimumab infusion is to take place.

14. Boys must practice abstinence, or if sexually active with a girl of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal   foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all boys must also not donate sperm during the study and for 6 months after receiving the last dose of study drug.

15. Subjects’ screening laboratory tests must meet the following criteria:

a. Hemoglobin: ≥8.0 g/dL (SI: ≥80 g/L; girls and boys, ages 2 to 11)

≥8.5 g/dL (SI: ≥85 g/L; girls, ages 12 to 18)

≥9.0 g/dL (SI: ≥90 g/L; boys, ages 12 to 18)

b. White blood cells (WBCs) ≥3.0 x 103 cells/μL (SI: ≥3.0 x 109 cells/L)

c. Neutrophils ≥1.5 x 103 cells/μL (SI: ≥1.5 x 109 cells/L)

d. Platelets ≥140 x 103 cells/μL (SI: ≥140 x 109 cells/L)

e. Serum transaminase levels not exceeding 1.2 x the upper limit of normal for the central laboratory:

-Aspartate aminotransferase (AST)

o ≤67 IU/L (girls, ages 2 to <4)

o ≤58 IU/L (girls, ages 4 to <7)

o ≤48 IU/L (girls, ages 7 to 18)

o ≤83 IU/L (boys, ages 2 to <4)

o ≤71 IU/L (boys, ages 4 to <7)

o ≤48 IU/L (boys, ages 7 to 18)

– Alanine aminotransferase (ALT)

o ≤41 IU/L (girls, ages 2 to 18)

o ≤41 IU/L (boys, ages 2 to <10)

o ≤42 IU/L (boys, ages 10 to 18)

f. Serum creatinine not to exceed:

– 0.5 mg/dL (SI: 44 μmol/L; ages 2 to 5)

– 0.7 mg/dL (SI: 62 μmol/L; ages 6 to 10)

– 1.0 mg/dL (SI: 88 μmol/L; ages 11 to 12)

– 1.2 mg/dL (SI: 106 μmol/L; ages ≥13)

16. Subjects must be up to date with all immunizations in agreement with current local immunization guidelines for immunosuppressed subjects before Week 0.

17. A parent or guardian must accompany the subject to each study visit until the subjects reaches the age of 18 years unless the subject is an emancipated juvenile.

18. The subject and his/her parent (if applicable) must be able to adhere to the study visit schedule, and understand and comply with other protocol requirements.

19. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

20. Each subject (or their legally acceptable representative) must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically 7 years of age and older and per local regulations) as described in Section 16.2.3, Informed Consent.

Exclusion Criteria

1. Subject has initiated DMARDs and/or immunosuppressive therapy within 4 weeks prior to first study agent administration.

2. Subject has been treated with intra-articular, intramuscular or intravenous corticosteroids (including intramuscular corticotropin) during the 4 weeks before first study agent administration.

3. Subject has been treated with any therapeutic agent targeted at reducing IL-12 or IL-23, including but not limited to ustekinumab and ABT-874 within 3 months
before first study agent administration.

4. Subject has been treated with natalizumab, efalizumab, or therapeutic agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) during the 12 months before first study agent administration, or have evidence at screening of persistent depletion of the targeted lymphocyte after receiving any of these agents.

5. Subject has been treated with alefacept within 3 months before first study agent administration.

6. Subject has been treated with abatacept within 8 weeks before first study agent administration.

7. Subject has been treated with leflunomide within 4 weeks before first study agent administration (irrespective of undergoing a drug elimination procedure), or have received leflunomide from 4 to 12 weeks before first study agent administration and have not undergone a drug elimination procedure.

8. Subject has been treated with cytotoxic agents, including cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.

9. Subject has received or is expected to receive any live viral or live bacterial vaccinations from 3 months before first study agent administration and up to 3 months after the last study agent administration.

10. Subject has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening or is planned to receive BCG vaccination within 12 months following last study drug administration.

11. Subject has received IL-1ra (anakinra) within 1 week of the first study agent administration.

12. Subjects has previously been treated with more than 1 therapeutic agent targeted at reducing TNFα, including, but not limited to, infliximab, etanercept, adalimumab, or certolizumab pegol.

13. If a subject has been previously treated with 1 anti-TNFα agent, the reason for discontinuation of the anti-TNFα agent cannot have been a severe or serious adverse event consistent with the class of anti-TNFα agents.

14. Subject has received adalimumab or certolizumab pegol within 6 weeks or has
received etanercept within 4 weeks of the first dose of study agent.

15. Subject has received infliximab or tocilizumab within 8 weeks of the first administration of study agent.

16. Subject has ever received IV or SC golimumab.

17. Subject has ever received a Janus Kinase (JAK) inhibitor, including but not limited to tofacitinib within 2 weeks of the first dose of study agent.

18. Subject has received canakinumab within 4 months prior to first study dose administration.

19. Subject has current side effects related to MTX or conditions which would preclude treatment with MTX, including but not limited to liver cirrhosis, liver fibrosis, persistent elevations of ALT and AST; more than 3 of 5 tests elevated within 6-months period), MTX pneumonitis, severe mucosal ulcers, intractable nausea, vomiting/diarrhea, evidence of clinically significant bone marrow suppression, severe headaches, severe bone pain, or traumatic fractures.

20. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 3 months or 5 half-lives, whichever is longer, before the planned first dose of study drug or is currently enrolled in an investigational study.

21. Subject has a history of active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criterion (Section 4.1) for information regarding eligibility with a history of latent TB.

22. Subject tests positive for hepatitis B virus (Attachment 3).

23. Subject is seropositive for antibodies to hepatitis C virus (HCV).

24. Subject has a known history of infection with human immunodeficiency virus (HIV).

25. Subject has had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, pneumocystis, or aspergillosis) within 6 months prior to screening.

26. Subject has a history of an infected joint prosthesis or has received antibiotics for a suspected infection of a joint prosthesis unless that prosthesis has been removed or replaced.

27. Subject has or has had a serious infection (including but not limited to hepatitis, pneumonia, or pyelonephritis), or have been hospitalized or received IV antibiotics for an infection during the 2 months before first study agent administration.

28. Subject has a history of or ongoing chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis), open, draining, or infected skin wound, or ulcer.

29. Subject has a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB (if applicable).

Malignancy or increased potential for malignancy:

30. Subject has a known malignancy or a history of malignancy.

31. Subject has a history of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location, or clinically significant splenomegaly not consistent with pJIA or systemic onset JIA without systemic symptoms.

Coexisting medical conditions or past medical history:

32. Subject has a history of severe progressive or uncontrolled liver or renal insufficiency; or significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances.

33. Subject has known allergies, hypersensitivity, or intolerance to golimumab or its excipients (refer to Investigator's Brochure) or subject has known allergies, hypersensitivity, or intolerance to immunoglobulins.

34. Subject has or has had a substance abuse (drug or alcohol) problem.

35. Subject has a history of macrophage activation syndrome.

36. Subject has another inflammatory disease that might confound the evaluation of benefit from golimumab therapy, including but not limited to systemic lupus erythematosus or Lyme disease.

37. Subject is incapacitated, largely or wholly bedridden, or confined to a wheelchair, or has little or no ability for age-appropriate self-care.

38. Subject has a known history of demyelinating diseases such as multiple sclerosis.

39. Subject has a history of or concomitant diagnosis of congestive heart failure.

Other:

40. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

41. Subject is a girl who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug

42. Subject is a boy who plans to father a child while enrolled in this study or within 6 months after the last dose of study drug.

43. Subject is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.

44. Subject is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.

45. Active uveitis within 3 months prior to screening

46. Subject with BSA >3.0 m2