1. MOVING THE TROOPS THROUGH Enrollment to Randomization

2. Logistics 6 Month treatment period – Visits at weeks 0, 2, 8, 16 and 26 5 year follow up period –1 year clinic visits –4 year telephone contact Central laboratory: All tests provided Central pharmacy: Aptuit Paper reports faxed to Core for data entry

3. Inclusion criteria Primary FSGS confirmed by renal biopsy or genetic testing Failure to respond to prior therapy at least one of the following immunosuppressive medications-cyclosporine, tacrolimus, MMF, sirolomus Age 1-65 years at onset of proteinuria Estimated GFR ≥40 ml/min/1.73 m2 at screening and ≥30 ml/min/1.73 m2 at randomization

4. Inclusion criteria Up/c > 1.0 g/g creatinine on first morning void Steroid resistance defined as failure to achieve sustained Up/c <1.0 following a standard course of prednisone/prednisolone/methylprednis olone OR contraindication/anticipated intolerance to steroid therapy.

5. Exclusion criteria Lactation, pregnancy, or refusal of birth control in women of child ‑ bearing potential Participation in another therapeutic trial involving protocol mandated administration of a immunosuppressive medication concurrently or 30 days prior to randomization Active/serious infection (including, but not limited to hepatitis B or C, HIV) History of malignancy Abnormality in age appropriate cancer screening in accord with ACS 2003 guidelines Uncontrolled BP > 140/95 or > 95th percentile for age/height at the end of the run in period Diabetes mellitus Type I or II.

6. Exclusion criteria Organ transplantation Congestive heart failure History of prior myocardial infarction SLE or multiple sclerosis Hepatic disease defined as serum AST/ALT >2.5X upper limit of normal Hematocrit <27% Immunosuppressive therapy with cyclosporine, Tacrolimus, MMF, azathioprine, rapamycin, or cyclophosphamide in the 30 days prior or Rituximab in the 90 days prior to randomization Prior treatment with adalimumab or galactose Allergy to study medications Abnormal pap smear (more than CIN I)

7. Screening visit History and Physical exam HIV, HEP B/C if not done in the past 12 months PPD if not done in the past 12 months All labs to Spectra, with 2 specimens for Up/c Existing renal biopsy tissue sent to study pathologist to confirm FSGS

8. Screening visit-key points Review all CRFs for completion/accuracy Ensure that the patient has a negative cancer screening according to the ACS 2003 guidelines Patients should be on target doses of lisinopril and losartan by the end of the screening period (prior to week 0 visit) Schedule week 0 visit once you have received drug from Aptuit

9. Abbreviated Screening Period If a subject is already on medication and has reached target doses of ACEi and ARB for a minimum of 2 weeks at the time of the B01 visit, the B02 visit will not be required. The B02 visit is held primarily for safety reasons. It is done to ensure that implementation of the combination of ACEi and ARB at the target doses does not cause a decline in GFR below 30 mL/min/1.73 m 2, the eligibility cut off. The subject will receive a screening GFR at B01 to ensure that a decline below 30 mL/min/1.73 m 2 has not occurred.

10. Cancer Screening Overview Age > 21 and female: Annual Pap smear. Age > 40 and female: Annual Pap smear AND mammogram. Age > 50: Annual screen for occult fecal blood. Age > 50 and male: Annual screen for occult fecal blood and PSA Cancer screening is essential because of the use of adalimumab

11. Medications Adalimumab (Humira) SQ injection every other week Dose is 24 mg/m 2 /dose Maximum dose 40 mg

12. Medications Galactose Powder mixed with water administered bid Dose is 0.2g/kg/dose Maximum dose 15 g

13. Medications DRUGWT ≤ 40 KGWT > 40 KG Lisinopril10 mg20 mg Losartan25 mg50 mg Atorvastatin10 mg20mg

14. Randomization Fax all forms to your core site for data entry Once your patient is randomized you will receive -initial prescription report -drug allocation report Drug will be shipped to your site from Aptuit within 1-2 business days

15. Drug Distribution Center (APTUIT) Drugs provided: Atorvastatin Galactose, Humira Prescription for: lisinopril and losartan Drugs will be shipped from Aptuit once patient is randomized

16. Central Laboratory (Spectra East) CBL measurements: Urine protein/creatinine, urine pregnancy testing, all serum chemistries, fasting lipid profile, hematology, Screening for HIV, HEP B, and HEP C Spectra to send kits with Fed Ex labels, shipping boxes, tubes, collection cups, ice packs, etc. Spectra faxes routine results to PSs, transmits results to central data base overnight. Immediate “panic reports” of life-threatening values

17. Visits All Forms are available on line https://clinicalresearch.ccf.org Visits should be held within 3 days on either side of target date Once week 0 visit is entered, a visit schedule will be sent to site

18. DCC Reports Eligibility (every other day until participant is randomized or considered ineligible) Core Lab (results of urine and or blood/serum samples sent to Spectra) Biopsy Results (sent when Core Pathologist completes/enters F287) AE/SAE (F260, F261 entered; this report will go to NIH Project Officer as well) Reminders (an e-mail stating next visit window and what is expected for that visit) Action Items (BP out-of-range, high or low lab values, etc) DCC e-mail alias is font_dcc@bio.ri.ccf.orgfont_dcc@bio.ri.ccf.org

19. REIMBURSEMENT $1250 per center start-up Effort for IRB application and contract –Pharmacy start-up –Administrative fees –Dispersed upon receipt of IRB approval and signed contract with Clinical Coordinating Center $3375 per patient enrolled